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Category Archives: Transhuman News
DNA repair – Wikipedia, the free encyclopedia
Posted: September 8, 2016 at 6:32 am
DNA damage resulting in multiple broken chromosomes
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA damage, resulting in as many as 1 million individual molecular lesions per cell per day.[1] Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells after it undergoes mitosis. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur, including double-strand breaks and DNA crosslinkages (interstrand crosslinks or ICLs).[2][3] This can eventually lead to malignant tumors, or cancer as per the two hit hypothesis.
The rate of DNA repair is dependent on many factors, including the cell type, the age of the cell, and the extracellular environment. A cell that has accumulated a large amount of DNA damage, or one that no longer effectively repairs damage incurred to its DNA, can enter one of three possible states:
The DNA repair ability of a cell is vital to the integrity of its genome and thus to the normal functionality of that organism. Many genes that were initially shown to influence life span have turned out to be involved in DNA damage repair and protection.[4]
The 2015 Nobel Prize in Chemistry was awarded to Tomas Lindahl, Paul Modrich, and Aziz Sancar for their work on the molecular mechanisms of DNA repair processes.[5][6]
DNA damage, due to environmental factors and normal metabolic processes inside the cell, occurs at a rate of 10,000 to 1,000,000 molecular lesions per cell per day.[1] While this constitutes only 0.000165% of the human genome's approximately 6 billion bases (3 billion base pairs), unrepaired lesions in critical genes (such as tumor suppressor genes) can impede a cell's ability to carry out its function and appreciably increase the likelihood of tumor formation and contribute to tumour heterogeneity.
The vast majority of DNA damage affects the primary structure of the double helix; that is, the bases themselves are chemically modified. These modifications can in turn disrupt the molecules' regular helical structure by introducing non-native chemical bonds or bulky adducts that do not fit in the standard double helix. Unlike proteins and RNA, DNA usually lacks tertiary structure and therefore damage or disturbance does not occur at that level. DNA is, however, supercoiled and wound around "packaging" proteins called histones (in eukaryotes), and both superstructures are vulnerable to the effects of DNA damage.
DNA damage can be subdivided into two main types:
The replication of damaged DNA before cell division can lead to the incorporation of wrong bases opposite damaged ones. Daughter cells that inherit these wrong bases carry mutations from which the original DNA sequence is unrecoverable (except in the rare case of a back mutation, for example, through gene conversion).
There are several types of damage to DNA due to endogenous cellular processes:
Damage caused by exogenous agents comes in many forms. Some examples are:
UV damage, alkylation/methylation, X-ray damage and oxidative damage are examples of induced damage. Spontaneous damage can include the loss of a base, deamination, sugar ring puckering and tautomeric shift.
In human cells, and eukaryotic cells in general, DNA is found in two cellular locations inside the nucleus and inside the mitochondria. Nuclear DNA (nDNA) exists as chromatin during non-replicative stages of the cell cycle and is condensed into aggregate structures known as chromosomes during cell division. In either state the DNA is highly compacted and wound up around bead-like proteins called histones. Whenever a cell needs to express the genetic information encoded in its nDNA the required chromosomal region is unravelled, genes located therein are expressed, and then the region is condensed back to its resting conformation. Mitochondrial DNA (mtDNA) is located inside mitochondria organelles, exists in multiple copies, and is also tightly associated with a number of proteins to form a complex known as the nucleoid. Inside mitochondria, reactive oxygen species (ROS), or free radicals, byproducts of the constant production of adenosine triphosphate (ATP) via oxidative phosphorylation, create a highly oxidative environment that is known to damage mtDNA. A critical enzyme in counteracting the toxicity of these species is superoxide dismutase, which is present in both the mitochondria and cytoplasm of eukaryotic cells.
Senescence, an irreversible process in which the cell no longer divides, is a protective response to the shortening of the chromosome ends. The telomeres are long regions of repetitive noncoding DNA that cap chromosomes and undergo partial degradation each time a cell undergoes division (see Hayflick limit).[10] In contrast, quiescence is a reversible state of cellular dormancy that is unrelated to genome damage (see cell cycle). Senescence in cells may serve as a functional alternative to apoptosis in cases where the physical presence of a cell for spatial reasons is required by the organism,[11] which serves as a "last resort" mechanism to prevent a cell with damaged DNA from replicating inappropriately in the absence of pro-growth cellular signaling. Unregulated cell division can lead to the formation of a tumor (see cancer), which is potentially lethal to an organism. Therefore, the induction of senescence and apoptosis is considered to be part of a strategy of protection against cancer.[12]
It is important to distinguish between DNA damage and mutation, the two major types of error in DNA. DNA damages and mutation are fundamentally different. Damages are physical abnormalities in the DNA, such as single- and double-strand breaks, 8-hydroxydeoxyguanosine residues, and polycyclic aromatic hydrocarbon adducts. DNA damages can be recognized by enzymes, and, thus, they can be correctly repaired if redundant information, such as the undamaged sequence in the complementary DNA strand or in a homologous chromosome, is available for copying. If a cell retains DNA damage, transcription of a gene can be prevented, and, thus, translation into a protein will also be blocked. Replication may also be blocked or the cell may die.
In contrast to DNA damage, a mutation is a change in the base sequence of the DNA. A mutation cannot be recognized by enzymes once the base change is present in both DNA strands, and, thus, a mutation cannot be repaired. At the cellular level, mutations can cause alterations in protein function and regulation. Mutations are replicated when the cell replicates. In a population of cells, mutant cells will increase or decrease in frequency according to the effects of the mutation on the ability of the cell to survive and reproduce. Although distinctly different from each other, DNA damages and mutations are related because DNA damages often cause errors of DNA synthesis during replication or repair; these errors are a major source of mutation.
Given these properties of DNA damage and mutation, it can be seen that DNA damages are a special problem in non-dividing or slowly dividing cells, where unrepaired damages will tend to accumulate over time. On the other hand, in rapidly dividing cells, unrepaired DNA damages that do not kill the cell by blocking replication will tend to cause replication errors and thus mutation. The great majority of mutations that are not neutral in their effect are deleterious to a cell's survival. Thus, in a population of cells composing a tissue with replicating cells, mutant cells will tend to be lost. However, infrequent mutations that provide a survival advantage will tend to clonally expand at the expense of neighboring cells in the tissue. This advantage to the cell is disadvantageous to the whole organism, because such mutant cells can give rise to cancer. Thus, DNA damages in frequently dividing cells, because they give rise to mutations, are a prominent cause of cancer. In contrast, DNA damages in infrequently dividing cells are likely a prominent cause of aging.[13]
Single-strand and double-strand DNA damage
Cells cannot function if DNA damage corrupts the integrity and accessibility of essential information in the genome (but cells remain superficially functional when non-essential genes are missing or damaged). Depending on the type of damage inflicted on the DNA's double helical structure, a variety of repair strategies have evolved to restore lost information. If possible, cells use the unmodified complementary strand of the DNA or the sister chromatid as a template to recover the original information. Without access to a template, cells use an error-prone recovery mechanism known as translesion synthesis as a last resort.
Damage to DNA alters the spatial configuration of the helix, and such alterations can be detected by the cell. Once damage is localized, specific DNA repair molecules bind at or near the site of damage, inducing other molecules to bind and form a complex that enables the actual repair to take place.
Cells are known to eliminate three types of damage to their DNA by chemically reversing it. These mechanisms do not require a template, since the types of damage they counteract can occur in only one of the four bases. Such direct reversal mechanisms are specific to the type of damage incurred and do not involve breakage of the phosphodiester backbone. The formation of pyrimidine dimers upon irradiation with UV light results in an abnormal covalent bond between adjacent pyrimidine bases. The photoreactivation process directly reverses this damage by the action of the enzyme photolyase, whose activation is obligately dependent on energy absorbed from blue/UV light (300500nm wavelength) to promote catalysis.[14] Photolyase, an old enzyme present in bacteria, fungi, and most animals no longer functions in humans,[15] who instead use nucleotide excision repair to repair damage from UV irradiation. Another type of damage, methylation of guanine bases, is directly reversed by the protein methyl guanine methyl transferase (MGMT), the bacterial equivalent of which is called ogt. This is an expensive process because each MGMT molecule can be used only once; that is, the reaction is stoichiometric rather than catalytic.[16] A generalized response to methylating agents in bacteria is known as the adaptive response and confers a level of resistance to alkylating agents upon sustained exposure by upregulation of alkylation repair enzymes.[17] The third type of DNA damage reversed by cells is certain methylation of the bases cytosine and adenine.
When only one of the two strands of a double helix has a defect, the other strand can be used as a template to guide the correction of the damaged strand. In order to repair damage to one of the two paired molecules of DNA, there exist a number of excision repair mechanisms that remove the damaged nucleotide and replace it with an undamaged nucleotide complementary to that found in the undamaged DNA strand.[16]
Double-strand breaks, in which both strands in the double helix are severed, are particularly hazardous to the cell because they can lead to genome rearrangements. Three mechanisms exist to repair double-strand breaks (DSBs): non-homologous end joining (NHEJ), microhomology-mediated end joining (MMEJ), and homologous recombination.[16] PVN Acharya noted that double-strand breaks and a "cross-linkage joining both strands at the same point is irreparable because neither strand can then serve as a template for repair. The cell will die in the next mitosis or in some rare instances, mutate."[2][3]
In NHEJ, DNA Ligase IV, a specialized DNA ligase that forms a complex with the cofactor XRCC4, directly joins the two ends.[21] To guide accurate repair, NHEJ relies on short homologous sequences called microhomologies present on the single-stranded tails of the DNA ends to be joined. If these overhangs are compatible, repair is usually accurate.[22][23][24][25] NHEJ can also introduce mutations during repair. Loss of damaged nucleotides at the break site can lead to deletions, and joining of nonmatching termini forms insertions or translocations. NHEJ is especially important before the cell has replicated its DNA, since there is no template available for repair by homologous recombination. There are "backup" NHEJ pathways in higher eukaryotes.[26] Besides its role as a genome caretaker, NHEJ is required for joining hairpin-capped double-strand breaks induced during V(D)J recombination, the process that generates diversity in B-cell and T-cell receptors in the vertebrate immune system.[27]
MMEJ starts with short-range end resection by MRE11 nuclease on either side of a double-strand break to reveal microhomology regions.[28] In further steps,[29] PARP1 is required and may be an early step in MMEJ. There is pairing of microhomology regions followed by recruitment of flap structure-specific endonuclease 1 (FEN1) to remove overhanging flaps. This is followed by recruitment of XRCC1LIG3 to the site for ligating the DNA ends, leading to an intact DNA.
DNA double strand breaks in mammalian cells are primarily repaired by homologous recombination (HR) and non-homologous end joining (NHEJ).[30] In an in vitro system, MMEJ occurred in mammalian cells at the levels of 1020% of HR when both HR and NHEJ mechanisms were also available.[28] MMEJ is always accompanied by a deletion, so that MMEJ is a mutagenic pathway for DNA repair.[31]
Homologous recombination requires the presence of an identical or nearly identical sequence to be used as a template for repair of the break. The enzymatic machinery responsible for this repair process is nearly identical to the machinery responsible for chromosomal crossover during meiosis. This pathway allows a damaged chromosome to be repaired using a sister chromatid (available in G2 after DNA replication) or a homologous chromosome as a template. DSBs caused by the replication machinery attempting to synthesize across a single-strand break or unrepaired lesion cause collapse of the replication fork and are typically repaired by recombination.
Topoisomerases introduce both single- and double-strand breaks in the course of changing the DNA's state of supercoiling, which is especially common in regions near an open replication fork. Such breaks are not considered DNA damage because they are a natural intermediate in the topoisomerase biochemical mechanism and are immediately repaired by the enzymes that created them.
A team of French researchers bombarded Deinococcus radiodurans to study the mechanism of double-strand break DNA repair in that bacterium. At least two copies of the genome, with random DNA breaks, can form DNA fragments through annealing. Partially overlapping fragments are then used for synthesis of homologous regions through a moving D-loop that can continue extension until they find complementary partner strands. In the final step there is crossover by means of RecA-dependent homologous recombination.[32]
Translesion synthesis (TLS) is a DNA damage tolerance process that allows the DNA replication machinery to replicate past DNA lesions such as thymine dimers or AP sites.[33] It involves switching out regular DNA polymerases for specialized translesion polymerases (i.e. DNA polymerase IV or V, from the Y Polymerase family), often with larger active sites that can facilitate the insertion of bases opposite damaged nucleotides. The polymerase switching is thought to be mediated by, among other factors, the post-translational modification of the replication processivity factor PCNA. Translesion synthesis polymerases often have low fidelity (high propensity to insert wrong bases) on undamaged templates relative to regular polymerases. However, many are extremely efficient at inserting correct bases opposite specific types of damage. For example, Pol mediates error-free bypass of lesions induced by UV irradiation, whereas Pol introduces mutations at these sites. Pol is known to add the first adenine across the T^T photodimer using Watson-Crick base pairing and the second adenine will be added in its syn conformation using Hoogsteen base pairing. From a cellular perspective, risking the introduction of point mutations during translesion synthesis may be preferable to resorting to more drastic mechanisms of DNA repair, which may cause gross chromosomal aberrations or cell death. In short, the process involves specialized polymerases either bypassing or repairing lesions at locations of stalled DNA replication. For example, Human DNA polymerase eta can bypass complex DNA lesions like guanine-thymine intra-strand crosslink, G[8,5-Me]T, although can cause targeted and semi-targeted mutations.[34] Paromita Raychaudhury and Ashis Basu[35] studied the toxicity and mutagenesis of the same lesion in Escherichia coli by replicating a G[8,5-Me]T-modified plasmid in E. coli with specific DNA polymerase knockouts. Viability was very low in a strain lacking pol II, pol IV, and pol V, the three SOS-inducible DNA polymerases, indicating that translesion synthesis is conducted primarily by these specialized DNA polymerases. A bypass platform is provided to these polymerases by Proliferating cell nuclear antigen (PCNA). Under normal circumstances, PCNA bound to polymerases replicates the DNA. At a site of lesion, PCNA is ubiquitinated, or modified, by the RAD6/RAD18 proteins to provide a platform for the specialized polymerases to bypass the lesion and resume DNA replication.[36][37] After translesion synthesis, extension is required. This extension can be carried out by a replicative polymerase if the TLS is error-free, as in the case of Pol , yet if TLS results in a mismatch, a specialized polymerase is needed to extend it; Pol . Pol is unique in that it can extend terminal mismatches, whereas more processive polymerases cannot. So when a lesion is encountered, the replication fork will stall, PCNA will switch from a processive polymerase to a TLS polymerase such as Pol to fix the lesion, then PCNA may switch to Pol to extend the mismatch, and last PCNA will switch to the processive polymerase to continue replication.
Cells exposed to ionizing radiation, ultraviolet light or chemicals are prone to acquire multiple sites of bulky DNA lesions and double-strand breaks. Moreover, DNA damaging agents can damage other biomolecules such as proteins, carbohydrates, lipids, and RNA. The accumulation of damage, to be specific, double-strand breaks or adducts stalling the replication forks, are among known stimulation signals for a global response to DNA damage.[38] The global response to damage is an act directed toward the cells' own preservation and triggers multiple pathways of macromolecular repair, lesion bypass, tolerance, or apoptosis. The common features of global response are induction of multiple genes, cell cycle arrest, and inhibition of cell division.
After DNA damage, cell cycle checkpoints are activated. Checkpoint activation pauses the cell cycle and gives the cell time to repair the damage before continuing to divide. DNA damage checkpoints occur at the G1/S and G2/M boundaries. An intra-S checkpoint also exists. Checkpoint activation is controlled by two master kinases, ATM and ATR. ATM responds to DNA double-strand breaks and disruptions in chromatin structure,[39] whereas ATR primarily responds to stalled replication forks. These kinases phosphorylate downstream targets in a signal transduction cascade, eventually leading to cell cycle arrest. A class of checkpoint mediator proteins including BRCA1, MDC1, and 53BP1 has also been identified.[40] These proteins seem to be required for transmitting the checkpoint activation signal to downstream proteins.
DNA damage checkpoint is a signal transduction pathway that blocks cell cycle progression in G1, G2 and metaphase and slows down the rate of S phase progression when DNA is damaged. It leads to a pause in cell cycle allowing the cell time to repair the damage before continuing to divide.
Checkpoint Proteins can be separated into four groups: phosphatidylinositol 3-kinase (PI3K)-like protein kinase, proliferating cell nuclear antigen (PCNA)-like group, two serine/threonine(S/T) kinases and their adaptors. Central to all DNA damage induced checkpoints responses is a pair of large protein kinases belonging to the first group of PI3K-like protein kinases-the ATM (Ataxia telangiectasia mutated) and ATR (Ataxia- and Rad-related) kinases, whose sequence and functions have been well conserved in evolution. All DNA damage response requires either ATM or ATR because they have the ability to bind to the chromosomes at the site of DNA damage, together with accessory proteins that are platforms on which DNA damage response components and DNA repair complexes can be assembled.
An important downstream target of ATM and ATR is p53, as it is required for inducing apoptosis following DNA damage.[41] The cyclin-dependent kinase inhibitor p21 is induced by both p53-dependent and p53-independent mechanisms and can arrest the cell cycle at the G1/S and G2/M checkpoints by deactivating cyclin/cyclin-dependent kinase complexes.[42]
The SOS response is the changes in gene expression in Escherichia coli and other bacteria in response to extensive DNA damage. The prokaryotic SOS system is regulated by two key proteins: LexA and RecA. The LexA homodimer is a transcriptional repressor that binds to operator sequences commonly referred to as SOS boxes. In Escherichia coli it is known that LexA regulates transcription of approximately 48 genes including the lexA and recA genes.[43] The SOS response is known to be widespread in the Bacteria domain, but it is mostly absent in some bacterial phyla, like the Spirochetes.[44] The most common cellular signals activating the SOS response are regions of single-stranded DNA (ssDNA), arising from stalled replication forks or double-strand breaks, which are processed by DNA helicase to separate the two DNA strands.[38] In the initiation step, RecA protein binds to ssDNA in an ATP hydrolysis driven reaction creating RecAssDNA filaments. RecAssDNA filaments activate LexA autoprotease activity, which ultimately leads to cleavage of LexA dimer and subsequent LexA degradation. The loss of LexA repressor induces transcription of the SOS genes and allows for further signal induction, inhibition of cell division and an increase in levels of proteins responsible for damage processing.
In Escherichia coli, SOS boxes are 20-nucleotide long sequences near promoters with palindromic structure and a high degree of sequence conservation. In other classes and phyla, the sequence of SOS boxes varies considerably, with different length and composition, but it is always highly conserved and one of the strongest short signals in the genome.[44] The high information content of SOS boxes permits differential binding of LexA to different promoters and allows for timing of the SOS response. The lesion repair genes are induced at the beginning of SOS response. The error-prone translesion polymerases, for example, UmuCD'2 (also called DNA polymerase V), are induced later on as a last resort.[45] Once the DNA damage is repaired or bypassed using polymerases or through recombination, the amount of single-stranded DNA in cells is decreased, lowering the amounts of RecA filaments decreases cleavage activity of LexA homodimer, which then binds to the SOS boxes near promoters and restores normal gene expression.
Eukaryotic cells exposed to DNA damaging agents also activate important defensive pathways by inducing multiple proteins involved in DNA repair, cell cycle checkpoint control, protein trafficking and degradation. Such genome wide transcriptional response is very complex and tightly regulated, thus allowing coordinated global response to damage. Exposure of yeast Saccharomyces cerevisiae to DNA damaging agents results in overlapping but distinct transcriptional profiles. Similarities to environmental shock response indicates that a general global stress response pathway exist at the level of transcriptional activation. In contrast, different human cell types respond to damage differently indicating an absence of a common global response. The probable explanation for this difference between yeast and human cells may be in the heterogeneity of mammalian cells. In an animal different types of cells are distributed among different organs that have evolved different sensitivities to DNA damage.[46]
In general global response to DNA damage involves expression of multiple genes responsible for postreplication repair, homologous recombination, nucleotide excision repair, DNA damage checkpoint, global transcriptional activation, genes controlling mRNA decay, and many others. A large amount of damage to a cell leaves it with an important decision: undergo apoptosis and die, or survive at the cost of living with a modified genome. An increase in tolerance to damage can lead to an increased rate of survival that will allow a greater accumulation of mutations. Yeast Rev1 and human polymerase are members of [Y family translesion DNA polymerases present during global response to DNA damage and are responsible for enhanced mutagenesis during a global response to DNA damage in eukaryotes.[38]
DNA repair rate is an important determinant of cell pathology
Experimental animals with genetic deficiencies in DNA repair often show decreased life span and increased cancer incidence.[13] For example, mice deficient in the dominant NHEJ pathway and in telomere maintenance mechanisms get lymphoma and infections more often, and, as a consequence, have shorter lifespans than wild-type mice.[47] In similar manner, mice deficient in a key repair and transcription protein that unwinds DNA helices have premature onset of aging-related diseases and consequent shortening of lifespan.[48] However, not every DNA repair deficiency creates exactly the predicted effects; mice deficient in the NER pathway exhibited shortened life span without correspondingly higher rates of mutation.[49]
If the rate of DNA damage exceeds the capacity of the cell to repair it, the accumulation of errors can overwhelm the cell and result in early senescence, apoptosis, or cancer. Inherited diseases associated with faulty DNA repair functioning result in premature aging,[13] increased sensitivity to carcinogens, and correspondingly increased cancer risk (see below). On the other hand, organisms with enhanced DNA repair systems, such as Deinococcus radiodurans, the most radiation-resistant known organism, exhibit remarkable resistance to the double-strand break-inducing effects of radioactivity, likely due to enhanced efficiency of DNA repair and especially NHEJ.[50]
Most life span influencing genes affect the rate of DNA damage
A number of individual genes have been identified as influencing variations in life span within a population of organisms. The effects of these genes is strongly dependent on the environment, in particular, on the organism's diet. Caloric restriction reproducibly results in extended lifespan in a variety of organisms, likely via nutrient sensing pathways and decreased metabolic rate. The molecular mechanisms by which such restriction results in lengthened lifespan are as yet unclear (see[51] for some discussion); however, the behavior of many genes known to be involved in DNA repair is altered under conditions of caloric restriction.
For example, increasing the gene dosage of the gene SIR-2, which regulates DNA packaging in the nematode worm Caenorhabditis elegans, can significantly extend lifespan.[52] The mammalian homolog of SIR-2 is known to induce downstream DNA repair factors involved in NHEJ, an activity that is especially promoted under conditions of caloric restriction.[53] Caloric restriction has been closely linked to the rate of base excision repair in the nuclear DNA of rodents,[54] although similar effects have not been observed in mitochondrial DNA.[55]
The C. elegans gene AGE-1, an upstream effector of DNA repair pathways, confers dramatically extended life span under free-feeding conditions but leads to a decrease in reproductive fitness under conditions of caloric restriction.[56] This observation supports the pleiotropy theory of the biological origins of aging, which suggests that genes conferring a large survival advantage early in life will be selected for even if they carry a corresponding disadvantage late in life.
Defects in the NER mechanism are responsible for several genetic disorders, including:
Mental retardation often accompanies the latter two disorders, suggesting increased vulnerability of developmental neurons.
Other DNA repair disorders include:
All of the above diseases are often called "segmental progerias" ("accelerated aging diseases") because their victims appear elderly and suffer from aging-related diseases at an abnormally young age, while not manifesting all the symptoms of old age.
Other diseases associated with reduced DNA repair function include Fanconi anemia, hereditary breast cancer and hereditary colon cancer.
Because of inherent limitations in the DNA repair mechanisms, if humans lived long enough, they would all eventually develop cancer.[57][58] There are at least 34 Inherited human DNA repair gene mutations that increase cancer risk. Many of these mutations cause DNA repair to be less effective than normal. In particular, Hereditary nonpolyposis colorectal cancer (HNPCC) is strongly associated with specific mutations in the DNA mismatch repair pathway. BRCA1 and BRCA2, two famous genes whose mutations confer a hugely increased risk of breast cancer on carriers, are both associated with a large number of DNA repair pathways, especially NHEJ and homologous recombination.
Cancer therapy procedures such as chemotherapy and radiotherapy work by overwhelming the capacity of the cell to repair DNA damage, resulting in cell death. Cells that are most rapidly dividing most typically cancer cells are preferentially affected. The side-effect is that other non-cancerous but rapidly dividing cells such as progenitor cells in the gut, skin, and hematopoietic system are also affected. Modern cancer treatments attempt to localize the DNA damage to cells and tissues only associated with cancer, either by physical means (concentrating the therapeutic agent in the region of the tumor) or by biochemical means (exploiting a feature unique to cancer cells in the body).
Classically, cancer has been viewed as a set of diseases that are driven by progressive genetic abnormalities that include mutations in tumour-suppressor genes and oncogenes, and chromosomal aberrations. However, it has become apparent that cancer is also driven by epigenetic alterations.[59]
Epigenetic alterations refer to functionally relevant modifications to the genome that do not involve a change in the nucleotide sequence. Examples of such modifications are changes in DNA methylation (hypermethylation and hypomethylation) and histone modification,[60] changes in chromosomal architecture (caused by inappropriate expression of proteins such as HMGA2 or HMGA1)[61] and changes caused by microRNAs. Each of these epigenetic alterations serves to regulate gene expression without altering the underlying DNA sequence. These changes usually remain through cell divisions, last for multiple cell generations, and can be considered to be epimutations (equivalent to mutations).
While large numbers of epigenetic alterations are found in cancers, the epigenetic alterations in DNA repair genes, causing reduced expression of DNA repair proteins, appear to be particularly important. Such alterations are thought to occur early in progression to cancer and to be a likely cause of the genetic instability characteristic of cancers.[62][63][64][65]
Reduced expression of DNA repair genes causes deficient DNA repair. When DNA repair is deficient DNA damages remain in cells at a higher than usual level and these excess damages cause increased frequencies of mutation or epimutation. Mutation rates increase substantially in cells defective in DNA mismatch repair[66][67] or in homologous recombinational repair (HRR).[68] Chromosomal rearrangements and aneuploidy also increase in HRR defective cells.[69]
Higher levels of DNA damage not only cause increased mutation, but also cause increased epimutation. During repair of DNA double strand breaks, or repair of other DNA damages, incompletely cleared sites of repair can cause epigenetic gene silencing.[70][71]
Deficient expression of DNA repair proteins due to an inherited mutation can cause increased risk of cancer. Individuals with an inherited impairment in any of 34 DNA repair genes (see article DNA repair-deficiency disorder) have an increased risk of cancer, with some defects causing up to a 100% lifetime chance of cancer (e.g. p53 mutations).[72] However, such germline mutations (which cause highly penetrant cancer syndromes) are the cause of only about 1 percent of cancers.[73]
Deficiencies in DNA repair enzymes are occasionally caused by a newly arising somatic mutation in a DNA repair gene, but are much more frequently caused by epigenetic alterations that reduce or silence expression of DNA repair genes. For example, when 113 colorectal cancers were examined in sequence, only four had a missense mutation in the DNA repair gene MGMT, while the majority had reduced MGMT expression due to methylation of the MGMT promoter region (an epigenetic alteration).[74] Five different studies found that between 40% and 90% of colorectal cancers have reduced MGMT expression due to methylation of the MGMT promoter region.[75][76][77][78][79]
Similarly, out of 119 cases of mismatch repair-deficient colorectal cancers that lacked DNA repair gene PMS2 expression, PMS2 was deficient in 6 due to mutations in the PMS2 gene, while in 103 cases PMS2 expression was deficient because its pairing partner MLH1 was repressed due to promoter methylation (PMS2 protein is unstable in the absence of MLH1).[80] In the other 10 cases, loss of PMS2 expression was likely due to epigenetic overexpression of the microRNA, miR-155, which down-regulates MLH1.[81]
In further examples (tabulated in Table 4 of this reference[82]), epigenetic defects were found at frequencies of between 13%-100% for the DNA repair genes BRCA1, WRN, FANCB, FANCF, MGMT, MLH1, MSH2, MSH4, ERCC1, XPF, NEIL1 and ATM. These epigenetic defects occurred in various cancers (e.g. breast, ovarian, colorectal and head and neck). Two or three deficiencies in the expression of ERCC1, XPF or PMS2 occur simultaneously in the majority of the 49 colon cancers evaluated by Facista et al.[83]
The chart in this section shows some frequent DNA damaging agents, examples of DNA lesions they cause, and the pathways that deal with these DNA damages. At least 169 enzymes are either directly employed in DNA repair or influence DNA repair processes.[84] Of these, 83 are directly employed in repairing the 5 types of DNA damages illustrated in the chart.
Some of the more well studied genes central to these repair processes are shown in the chart. The gene designations shown in red, gray or cyan indicate genes frequently epigenetically altered in various types of cancers. Wikipedia articles on each of the genes high-lighted by red, gray or cyan describe the epigenetic alteration(s) and the cancer(s) in which these epimutations are found. Two review articles,[82][85] and two broad experimental survey articles[86][87] also document most of these epigenetic DNA repair deficiencies in cancers.
Red-highlighted genes are frequently reduced or silenced by epigenetic mechanisms in various cancers. When these genes have low or absent expression, DNA damages can accumulate. Replication errors past these damages (see translesion synthesis) can lead to increased mutations and, ultimately, cancer. Epigenetic repression of DNA repair genes in accurate DNA repair pathways appear to be central to carcinogenesis.
The two gray-highlighted genes RAD51 and BRCA2, are required for homologous recombinational repair. They are sometimes epigenetically over-expressed and sometimes under-expressed in certain cancers. As indicated in the Wikipedia articles on RAD51 and BRCA2, such cancers ordinarily have epigenetic deficiencies in other DNA repair genes. These repair deficiencies would likely cause increased unrepaired DNA damages. The over-expression of RAD51 and BRCA2 seen in these cancers may reflect selective pressures for compensatory RAD51 or BRCA2 over-expression and increased homologous recombinational repair to at least partially deal with such excess DNA damages. In those cases where RAD51 or BRCA2 are under-expressed, this would itself lead to increased unrepaired DNA damages. Replication errors past these damages (see translesion synthesis) could cause increased mutations and cancer, so that under-expression of RAD51 or BRCA2 would be carcinogenic in itself.
Cyan-highlighted genes are in the microhomology-mediated end joining (MMEJ) pathway and are up-regulated in cancer. MMEJ is an additional error-prone inaccurate repair pathway for double-strand breaks. In MMEJ repair of a double-strand break, an homology of 5-25 complementary base pairs between both paired strands is sufficient to align the strands, but mismatched ends (flaps) are usually present. MMEJ removes the extra nucleotides (flaps) where strands are joined, and then ligates the strands to create an intact DNA double helix. MMEJ almost always involves at least a small deletion, so that it is a mutagenic pathway.[88]FEN1, the flap endonuclease in MMEJ, is epigenetically increased by promoter hypomethylation and is over-expressed in the majority of cancers of the breast,[89] prostate,[90] stomach,[91][92] neuroblastomas,[93] pancreas,[94] and lung.[95] PARP1 is also over-expressed when its promoter region ETS site is epigenetically hypomethylated, and this contributes to progression to endometrial cancer,[96] BRCA-mutated ovarian cancer,[97] and BRCA-mutated serous ovarian cancer.[98] Other genes in the MMEJ pathway are also over-expressed in a number of cancers (see MMEJ for summary), and are also shown in cyan.
The basic processes of DNA repair are highly conserved among both prokaryotes and eukaryotes and even among bacteriophage (viruses that infect bacteria); however, more complex organisms with more complex genomes have correspondingly more complex repair mechanisms.[99] The ability of a large number of protein structural motifs to catalyze relevant chemical reactions has played a significant role in the elaboration of repair mechanisms during evolution. For an extremely detailed review of hypotheses relating to the evolution of DNA repair, see.[100]
The fossil record indicates that single-cell life began to proliferate on the planet at some point during the Precambrian period, although exactly when recognizably modern life first emerged is unclear. Nucleic acids became the sole and universal means of encoding genetic information, requiring DNA repair mechanisms that in their basic form have been inherited by all extant life forms from their common ancestor. The emergence of Earth's oxygen-rich atmosphere (known as the "oxygen catastrophe") due to photosynthetic organisms, as well as the presence of potentially damaging free radicals in the cell due to oxidative phosphorylation, necessitated the evolution of DNA repair mechanisms that act specifically to counter the types of damage induced by oxidative stress.
On some occasions, DNA damage is not repaired, or is repaired by an error-prone mechanism that results in a change from the original sequence. When this occurs, mutations may propagate into the genomes of the cell's progeny. Should such an event occur in a germ line cell that will eventually produce a gamete, the mutation has the potential to be passed on to the organism's offspring. The rate of evolution in a particular species (or, in a particular gene) is a function of the rate of mutation. As a consequence, the rate and accuracy of DNA repair mechanisms have an influence over the process of evolutionary change.[101] Since the normal adaptation of populations of organisms to changing circumstances (for instance the adaptation of the beaks of a population of finches to the changing presence of hard seeds or insects) proceeds by gene regulation and the recombination and selection of gene variations alleles and not by passing on irreparable DNA damages to the offspring,[102] DNA damage protection and repair does not influence the rate of adaptation by gene regulation and by recombination and selection of alleles. On the other hand, DNA damage repair and protection does influence the rate of accumulation of irreparable, advantageous, code expanding, inheritable mutations, and slows down the evolutionary mechanism for expansion of the genome of organisms with new functionalities. The tension between evolvability and mutation repair and protection needs further investigation.
A technology named clustered regularly interspaced short palindromic repeat shortened to CRISPR-Cas9 was discovered in 2012. The new technology allows anyone with molecular biology training to alter the genes of any species with precision.[103]
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What Happens When We All Live to 100? – The Atlantic
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For millennia, if not for eonsanthropology continuously pushes backward the time of human originlife expectancy was short. The few people who grew old were assumed, because of their years, to have won the favor of the gods. The typical person was fortunate to reach 40.
Beginning in the 19th century, that slowly changed. Since 1840, life expectancy at birth has risen about three months with each passing year. In 1840, life expectancy at birth in Sweden, a much-studied nation owing to its record-keeping, was 45 years for women; today its 83 years. The United States displays roughly the same trend. When the 20th century began, life expectancy at birth in America was 47 years; now newborns are expected to live 79 years. If about three months continue to be added with each passing year, by the middle of this century, American life expectancy at birth will be 88 years. By the end of the century, it will be 100 years.
Viewed globally, the lengthening of life spans seems independent of any single, specific event. It didnt accelerate much as antibiotics and vaccines became common. Nor did it retreat much during wars or disease outbreaks. A graph of global life expectancy over time looks like an escalator rising smoothly. The trend holds, in most years, in individual nations rich and poor; the whole world is riding the escalator.
Projections of ever-longer life spans assume no incredible medical discoveriesrather, that the escalator ride simply continues. If anti-aging drugs or genetic therapies are found, the climb could accelerate. Centenarians may become the norm, rather than rarities who generate a headline in the local newspaper.
Pie in the sky? On a verdant hillside in Marin County, Californiahome to hipsters and towering redwoods, the place to which the Golden Gate Bridge leadssits the Buck Institute, the first private, independent research facility dedicated to extending the human life span. Since 1999, scientists and postdocs there have studied ways to make organisms live much longer, and with better health, than they naturally would. Already, the institutes researchers have quintupled the life span of laboratory worms. Most Americans have never heard of the Buck Institute, but someday this place may be very well known.
Buck is not alone in its pursuit. The University of Michigan, the University of Texas, and the University of California at San Francisco are studying ways to slow aging, as is the Mayo Clinic. Late in 2013, Google brought its trove of cash into the game, founding a spin-off called the California Life Company (known as Calico) to specialize in longevity research. Six months after Calicos charter was announced, Craig Venter, the biotech entrepreneur who in the 1990s conducted a dramatic race against government laboratories to sequence the human genome, also founded a start-up that seeks ways to slow aging.
Should research find a life-span breakthrough, the proportion of the U.S. population that is elderlyfated to rise anyway, considering declining fertility rates, the retirement of the Baby Boomers, and the continuing uplift of the escalatormay climb even more. Longer life has obvious appeal, but it entails societal risks. Politics may come to be dominated by the old, who might vote themselves ever more generous benefits for which the young must pay. Social Security and private pensions could be burdened well beyond what current actuarial tables suggest. If longer life expectancy simply leads to more years in which pensioners are disabled and demand expensive services, health-care costs may balloon as never before, while other social needs go unmet.
With each passing year, the newly born live about three months longer than those born the prior year.
But the story might have a happy ending. If medical interventions to slow aging result in added years of reasonable fitness, life might extend in a sanguine manner, with most men and women living longer in good vigor, and also working longer, keeping pension and health-care subsidies under control. Indeed, the most-exciting work being done in longevity science concerns making the later years vibrant, as opposed to simply adding time at the end.
Postwar medical research has focused on specific conditions: there are heart-disease laboratories, cancer institutes, and so on. Traditional research assumes the chronic later-life diseases that are among the nations leading killerscardiovascular blockage, stroke, Alzheimersarise individually and should be treated individually. What if, instead, aging is the root cause of many chronic diseases, and aging can be slowed? Not just life span but health span might increase.
Drugs that lengthen health span are becoming to medical researchers what vaccines and antibiotics were to previous generations in the lab: their grail. If health-span research is successful, pharmaceuticals as remarkable as those earlier generations of drugs may result. In the process, society might learn the answer to an ancient mystery: Given that every cell in a mammals body contains the DNA blueprint of a healthy young version of itself, why do we age at all?
Here in our freezers we have 100 or so compounds that extend life in invertebrates, says Gordon Lithgow, a geneticist at the Buck Institute. He walks with me through labs situated on a campus of modernistic buildings that command a dreamlike view of San Pablo Bay, and encourage dreamlike thoughts. The 100 compounds in the freezer? What we dont know is if they work in people.
The Buck Institute bustles with young researchers. Jeans and San Francisco 49ers caps are common sightsthis could be a Silicon Valley software start-up were not microscopes, cages, and biological-isolation chambers ubiquitous. The institute is named for Leonard and Beryl Buck, a Marin County couple who left oil stocks to a foundation charged with studying why people age, among other issues. When the institute opened, medical research aimed at slowing aging was viewed as quixoticthe sort of thing washed-up hippies talk about while sipping wine and watching the sunset. A mere 15 years into its existence, the Buck Institute is at the bow wave of biology.
In one lab, researchers laboriously tamper with yeast chromosomes. Yeast is expedient as a research subject because it lives out a lifetime before an analysts eyes, and because a third of yeast genes are similar to human genes. Deleting some genes kills yeast; deleting others causes yeast to live longer. Why deleting some genes extends life isnt knownBuck researchers are trying to figure this out, in the hope that they might then carry the effect over to mammals. The work is painstaking, with four microscopes in use at least 50 hours a week.
Buck employs Lilliputian electrocardiogram machines and toy-size CT scanners to examine the internal organs of mice, since the goal is not just to make them live longer but to keep them healthy longer, with less cancer or heart disease. Researchers curious about aging mainly work with mice, worms, flies, and yeast, because they are small and easily housed, and because they dont live long, so improvements to life expectancy are quickly observable. Twenty years ago it was a really big deal to extend the life span of worms. Now any postdoc can do that, says Simon Melov, a Buck geneticist. Experiments funded by the National Institute on Aging have shown that drugs can extend a mouses life span by about a quarter, and Buck researchers have been able to reverse age-related heart dysfunction in the same animal. Think how the world would be upended if human longevity quickly jumped another 25 percent.
The rubber will meet the road with human trials. We hope to find five to 10 small molecules that extend healthy life span in mice, then stage a human trial, says Brian Kennedy, the Buck Institutes CEO. A drug called rapamycinbeing tested at the institute and elsewhereseems closest to trial stage and has revolutionary potential. But in addition to being ethically fraught, human trials of a life-extension substance will be costly, and might take decades. The entry of Googles billions into the field makes human trials more likely. Calico is tight-lipped about its plansthe company agreed to let me visit, then backed out.
Anti-aging research is not without antecedents, some of which offer notes of caution. A generation ago, Linus Pauling, a winner of the Nobel Prize in chemistry, proposed that megadoses of vitamin C would retard aging. It turned out that at megadoses, vitamins can become toxic. If you take vitamins, swallow the amounts recommended by the Food and Drug Administration.
A decade ago, a biotech start-up called Sirtris sought to devise drugs that mimic the supposed health-giving properties of red wine. GlaxoSmithKline bought Sirtris for $790 million in todays dollars, money the company may wish it had back: Sirtris experiments have yet to lead to any practical product.
About 15 years ago, Bruce Ames, an accomplished scientist at the University of California at Berkeley, proposed that acetylcarnitine, which regulates the mitochondria of cells, combined with an antioxidant, might retard aging while treating mild Alzheimers. Antioxidant has become a buzzword of supplement marketing and Dr. Ozstyle quackery. Too much antioxidant would be unhealthy, since oxidation is essential to the bodys respiration. Ames thought he had found a compound that safely moderates the pace at which cells use themselves up. He began dosing himself with acetylcarnitine, and continues to work at Berkeley, at age 85; whether he would have enjoyed such longevity anyway is unknowable. Pharmaceutical companies have shown little interest in Amess ideabecause it occurs naturally, acetylcarnitine cannot be patented, and, worse from Big Pharmas standpoint, the substance is inexpensive.
Today, lab results show a clear relationship between a restricted-calorie diet and longevity in mice. That eating less extends the life spans of small mammals is the strongest finding of anti-aging research to this point. A restrictive diet seems to put mouse cells into a state vaguely similar to hibernation; whether caloric restriction would work in people isnt known. A campaign against calories might seem to possess broad practical appeal, since whats recommendedeating lesscosts nothing. But if the mice are any indication, one would need to eat a lot less, dropping caloric intake to the level at which a person feels hunger pangs throughout the day. Caloric restriction is a fad diet in Northern California, Melov told me. We had a caloric-restriction group come in to visit the institute. They did not look at all healthy.
Recently, separate teams at Harvard, Stanford, and UC San Francisco reported that transferring the blood of adolescent mice into old, declining mice had a rejuvenating effect on the latter. The thought of the old rich purchasing blood from the young poor is ghoulish on numerous levels. The research goal is to determine what chemical aspect of youthful blood benefits mature tissue. Perhaps compounds in adolescent blood excite dormant stem cells, and a drug could be developed that triggers the effect without transfusion.
The Buck Institute and other labs have been looking for health-span DNA that may exist in other mammals. Whales are a lot less likely than people are to get cancer. Polar bears consume an extremely high-fat diet yet dont develop arterial plaque. If the biological pathways for such qualities were understood, a drug might be designed to trigger the effect in people. Mimicking what nature has already developed seems more promising than trying to devise novel DNA.
In worms, genes called daf-2 and daf-16 can change in a way that causes the invertebrates to live twice as long as is natural, and in good vigor. A molecular biologist named Cynthia Kenyon, among the first hires at Calico, made that discovery more than two decades ago, when she was a researcher at UC San Francisco. By manipulating the same genes in mice, Kenyon has been able to cause them to live longer, with less cancer than mice in a control group: that is, with a better health span. The daf-16 gene is similar to a human gene called foxo3, a variant of which is linked to exceptional longevity. A drug that mimics this foxo3 variant is rumored to be among Calicos initial projects.
A long time has passed since Kenyons eureka moment about worm genes, and shes still far from proving that this insight can help people. But the tempo of the kind of work she does is accelerating. Twenty years ago, genetic sequencing and similar forms of DNA research were excruciatingly time-consuming. New techniques and equipment have altered that: for instance, one Silicon Valley lab-services firm, Sequetech, advertises, Go from [cell] colony to sequence in a day. The accelerating pace of genetic-information gathering may come in handy for health-span research.
The Buck Institute became cautiously optimistic about rapamycin when its life-extension properties were noticed in yeast. Lab mice dosed with rapamycin are dying off more slowly than they would naturally, and many of the old mice appear energetic and youthful. Devised to prevent rejection of transplanted organs, rapamycin seems to alter some chemistry associated with cellular senescence. (More on that later.) If the drug turns out to delay aging in people, it would be the greatest off-label pharmaceutical use ever. But dont ask your doctor for a prescriptionhealth-span therapy based on rapamycin is years away, if it ever happens. Kennedy, the Buck Institute CEO, does not dose himself with rapamycin, whose side effects are not understood.
Researchers at the Buck Institute are lean: societys obesity problems are not in evidence there. Everyone takes the stairs; elevators are viewed as strictly for visitors. If there is a candy machine on the 488-acre grounds, it is well hidden. I met some researchers for lunch in a glass-and-chrome conference room (Bucks buildings were designed by I. M. Pei and fairly shout Give me an architecture award!). Lunch was an ascetic affair: water and a small sandwich with greens; no sides, soda, or cookies. Kennedy says he seldom eats lunch, and runs up to 20 miles weekly. Yet, even doing everything right by the lights of current assumptions about how to stave off aging, at age 47, Kennedy has wrinkle lines around his eyes.
Except with regard to infectious diseases, medical cause and effect is notoriously hard to pin down. Coffee, salt, butter: good, bad, or neither? Studies are inconclusive. Why do some people develop heart disease while others with the same habits dont? The Framingham Heart Study, in its 66th year and following a third generation of subjects, still struggles with such questions. You should watch your weight, eat more greens and less sugar, exercise regularly, and get ample sleep. But you should do these things because they are common sensenot because there is any definitive proof that they will help you live longer.
The uncertainty inherent in the practice of medicine is amplified when the subject is longevity, because decades might pass before anyone knows whether a particular drug or lifestyle modification does any good. Scrutinizing the very old has not been the gold mine some researchers hoped it would be. Lifestyle studies of centenarians can be really puzzling, Kennedy says. They smoke more and drink less than we might guess. Few are vegetarians. Nothing jumps out as a definitive cause of their long lives.
Among the first wide-scale efforts to understand gerontology was the Baltimore Longitudinal Study of Aging, begun by federal researchers in 1958 and ongoing. Its current director, Luigi Ferrucci, says, The study has determined that disabilities among the elderly often have warning signs that can be detected in youth, and this insight might lead to early-life interventions that decrease late-life chronic disease. But on some of the big questions, such as whether longevity is caused mainly by genes or mainly by lifestyle and environment, we just have no idea at all.
Studies of twins suggest that about 30 percent of longevity is inherited. This is one of the factors that make researchers optimisticif 30 percent of longevity is inherited, perhaps laboratories can design a compound that causes anyones blood chemistry to mimic what happens in the bodies of those who were born with the DNA for long life. But when we sequence the genome, only 1 percent seems linked to longevity, Ferrucci told me. The other 99 percent of the presumed genetic effect is unexplained.
At medical conferences, Ferrucci likes to show physicians and researchers an elaborate medical profile of an anonymous patient, then ask them to guess her age. Guesses are off by as much as 20 years too high or low, he says. This is because medically, we do not know what age is. The sole means to determine age is by asking for date of birth. Thats what a basic level this research still is at.
Aging brings with it, of course, senescence. Cellular senescence, a subset of the overall phenomenon, is a subject of fascination in longevity research.
The tissues and organs that make up our bodies are prone to injury, and the cells are prone to malfunctions, cancer being the most prominent. When an injury must be healed, or cancerous tissue that is dividing must be stopped, nearby cells transmit chemical signals that trigger the repair of injured cells or the death of malignant ones. (Obviously this is a simplification.) In the young, the system works pretty well. But as cells turn senescent, they begin to send out false positives. The bodys healing ability falters as excess production of the repair signal leads to persistent inflammation, which is the foundation of heart disease, Alzheimers, arthritis, and other chronic maladies associated with the passage of time. Cars wear out because they cannot repair themselves; our bodies wear out because they lose the ability to repair themselves. If the loss of our ability to self-repair were slowed down, health during our later years would improve: a longer warranty, in the auto analogy.
If we can figure out how to eliminate senescent cells or switch off their secretions, says Judith Campisi, who runs the Buck Institutes research on this topic, then we could prevent or lessen the impact of many chronic diseases of aging. Its not a coincidence that incidence of these chronic diseases increases sharply after the age of 50, a time when senescent cells also increase in number. If you believe, as many scientists do, that aging is a prime cause of many chronic diseases, it is essential that we understand the accumulation of senescent cells. Rapamycin excites longevity researchers because it seems to switch off the repair signal mistakenly sent by senescent cells. Mayo Clinic researchers are studying other substances that dampen the effects of cellular senescence; some have proved to keep mice fit longer than normal, extending their health span. Many elderly people decline into years of progressive disability, then become invalids. If instead most people enjoyed reasonable vigor right up to the end, that would be just as exciting for society as adding years to life expectancy.
Big medical efforts tend to be structured as assaults on specific conditionsthe war on cancer and so on. One reason is psychological: a wealthy person who survived a heart attack, or lost a parent to one, endows a foundation to study the problem. Another reason is symbolic: we tend to view diseases as challenges thrown at us by nature, to be overcome one by one. If the passage of time itself turns out to be the challenge, interdisciplinary study of aging might overtake the disease-by-disease approach. As recently as a generation ago, it would have seemed totally crazy to suppose that aging could be cured. Now curing aging seems, well, only somewhat crazy.
The life-expectancy escalator has for nearly two centuries risen about three months a year, despite two world wars, the 1918 influenza pandemic, the AIDS epidemic, and the global populations growing sevenfoldthe latter deceptively important, because crowded conditions are assumed to more readily communicate disease. Will life-span increases continue regardless of what may happen in biotech? The yea position is represented by James Vaupel, the founder of Germanys Max Planck Institute for Demographic Research; the nay by Jay Olshansky, a professor of public health at the University of Illinois at Chicago.
In 2002, Vaupel published an influential article in Science documenting the eerily linear rise in life expectancy since 1840. Controversially, Vaupel concluded that reductions in mortality should not be seen as a disconnected sequence of unrepeatable revolutions but rather as a regular stream of continuing progress. No specific development or discovery has caused the rise: improvements in nutrition, public health, sanitation, and medical knowledge all have helped, but the operative impetus has been the stream of continuing progress.
Vaupel called it a reasonable scenario that increases will continue at least until life expectancy at birth surpasses 100. His views havent changed. The data still support the conclusions of the 2002 paper. Linear rise in life expectancy has continued, Vaupel told me earlier this year. In a recent report, the Centers for Disease Control and Prevention found that the age-adjusted U.S. death rate declined to a record low in 2011. Today the first four causes of death in the United States are chronic, age-related conditions: heart disease, cancer, chronic lower-respiratory diseases, and stroke. As long as living standards continue to improve, Vaupel thinks, life expectancy will continue to increase.
On the opposite side of this coin, Olshansky told me the rise in life expectancy will hit a wall soon, if it hasnt already. He noted, Most of the 20th-century gains in longevity came from reduced infant mortality, and those were onetime gains. Infant mortality in the United States trails some other nations, but has dropped so muchdown to one in 170that little room for improvement remains. Theres tremendous statistical impact on life expectancy when the young are saved, Olshansky says. A reduction in infant mortality saves the entire span of a persons life. Avoiding mortality in a young personsay, by vaccinesaves most of the persons life. Changes in medicine or lifestyle that extend the lives of the old dont add much to the numbers. Olshansky calculates that if cancer were eliminated, American life expectancy would rise by only three years, because a host of other chronic fatal diseases are waiting to take its place. He thinks the 21st century will see the average life span extend another 10 years or so, with a bonus of more health span. Then the increase will slow noticeably, or stop.
Whether human age may have a biological limit does not factor into this debate. A French woman who lived from 1875 to 1997, Jeanne Calment, had the longest confirmed life span, at 122. Shes obviously an outlier, and while outliers dont tell us much, they do hint at whats possible. Her age at death was well beyond the average life span that either Vaupel or Olshansky are contemplating in their analyses. And in any case, various experts, at various times across the past century, have argued that life span was nearing a ceiling, only to be proved wrong.
Diminishing smoking and drunk driving have obviously contributed to declining mortality. Homicide has fallen so muchshootings arent necessarily down, but improved trauma response saves more victimsthat murder is no longer among the top 15 causes of death in the United States. Other health indicators seem positive as well. All forms of harmful air and water emissions except greenhouse gases are in long-term decline. Less smog, acid rain, and airborne soot foster longevitythe old are sensitive to respiratory diseasewhile declining levels of industrial toxins may contribute to declining cancer rates. Life expectancy can be as much as 18 years shorter in low-income U.S. counties than in high-income counties, but Obamacare should correct some of that imbalance: Romneycare, enacted in 2006 and in many ways Obamacares precursor, reduced mortality in low-income Massachusetts counties. These and many other elements of Vaupels stream of continuing progress seem to favor longevity. So does climate change: people live longer in warm climates than cold, and the world is warming.
Popular attention tends to focus on whether what we gulp down determines how long we live: Should people take fish oil and shop for organic probiotic kefir? The way our homes, families, and friendships are organized may matter just as much. Thomas Perls, a professor at Boston Medical Center who analyzes the genomes of centenarians, notes that Seventh-Day Adventists enjoy about a decade more life expectancy than peers of their birth years: They dont drink or smoke, most are vegetarians, they exercise regularly even when old, and take a true weekly day of rest. But what really strikes Perls about Seventh-Day Adventists is that they maintain large social groups. Constant interaction with other people can be annoying, but overall seems to keep us engaged with life.
For years, the American social trend has been away from constant interaction with other peoplefewer two-parent homes, fewer children per home, declining participation in religious and community activities, grandparents living on their own, electronic interaction replacing the face-to-face in everything from work to dating. Prosperity is associated with smaller households, yet the large multigeneration home may be best for long life. There are some indications that the Great Recession increased multigeneration living. This may turn out to boost longevity, at least for a time.
The single best yardstick for measuring a persons likely life span is education. John Rowe, a health-policy professor at Columbia University and a former CEO of Aetna, says, If someone walked into my office and asked me to predict how long he would live, I would ask two things: What is your age, and how many years of education did you receive?
Jay Olshanskys latest research suggests that American women with no high-school diploma have experienced relatively small life-span increases since the 1950s, while the life expectancy of highly educated women has soared since then. Today the best-educated Americans live 10 to 14 years longer than the least educated, on average. Nothing pops out of the data like the link between education and life expectancy, Olshansky says. The good news is that the share of the American population that is less educated is in gradual decline. The bad news is that lack of education seems even more lethal than it was in the past.
Education does not sync with life expectancy because reading Dostoyevsky lowers blood pressure; college is a proxy for other aspects of a persons life. Compared with the less educated, people with a bachelors degree have a higher income, smoke less, are less likely to be overweight, and are more likely to follow doctors instructions. College graduates are more likely to marry and stay married, and marriage is good for your health: the wedded suffer fewer heart attacks and strokes than the single or divorced.
Many of the social developments that improve longevitybetter sanitation, less pollution, improved emergency roomsare provided to all on an egalitarian basis. But todays public high schools are dreadful in many inner-city areas, and broadly across states including California. Legislatures are cutting support for public universities, while the cost of higher education rises faster than inflation. These issues are discussed in terms of fairness; perhaps health should be added as a concern in the debate. If education is the trump card of longevity, the top quintile may pull away from the rest.
Society is dominated by the oldold political leaders, old judges. With each passing year, as longevity increases, the intergenerational imbalance worsens. The old demand benefits for which the young must pay, while people in their 20s become disenchanted, feeling that the deck is stacked against them. National debt increases at an alarming rate. Innovation and fresh thinking disappear as energies are devoted to defending current pie-slicing arrangements.
This isnt a prediction about the future of the United States, but rather a description of Japan right now. The Land of the Rising Sun is the worlds grayest nation. Already the median age is 45 (in the U.S., by comparison, it is 37), and it will jump to 55 by 2040. As Nicholas Eberstadt, a demographer at the American Enterprise Institute, has noted, median age in the retirement haven of Palm Springs, California, is currently 52 years. Japan is on its way to becoming an entire nation of Palm Springs residents.
The number of Americans 65 or older could reach 108 million in 2050. Thats like adding three more Floridas, inhabited entirely by seniors.
Japans grayness stems from a very low fertility ratenot enough babies to bring down the average ageand strict barriers against immigration. The United States remains a nation of immigrants, and because of the continual inflow of young people, the U.S. median age wont go haywire even as life expectancy rises: the United Nations World Population Prospects estimates that the U.S. median age will rise to 41 by mid-century.
Nonetheless, that Japan is the first major nation to turn gray, and is also the deepest in debt, is not encouraging. Once, Japan was feared as the Godzilla of global trade, but as it grayed, its economy entered a long cycle of soft growth. In 2012 the centrist Democratic Party of Japan, then holding the Diet, backed a tax whose goal was not to pay down what the country owes but merely to slow the rate of borrowing. The party promptly got the heave-ho from voters. Last year Japans public debt hit $10 trillion, twice the nations GDP.
Sheila Smith, a Japan specialist at the Council on Foreign Relations, told me, Young people in Japan have some of the worlds worst voter-participation rates. They think the old have the system so rigged in their favor, theres no point in political activity. The young dont seem excited by the future. News accounts of young Japanese becoming so apathetic that theyve lost interest in having sex sound hard to believe, but may bear some truth.
Young urban Japanese surely are aware that their elders are ringing up bills to be handed to them, but theyre also aware that if funding for the retired is cut, Grandma may want to move into their very small apartment. As life expectancy rises, a Japanese person entering the happy-go-lucky phase of early adulthood may find that parents and grandparents both expect to be looked after. Because the only child is common in Japans newest generation, a big cast of aging people may turn to one young person for financial support or caregiving or both. Acceding to public borrowing may have become, to young Japanese, a way to keep older generations out of the apartmenteven if it means crushing national debt down the road.
That America may become more like Japansteadily older, with rising debt and declining economic growthis unsettling. From the second half of the George W. Bush administration until 2013, U.S. national debt more than doubled. The federal government borrowed like there was no tomorrow. The debt binge, for which leaders of both political parties bear blame, was a prelude to the retirement of the Baby Boomers. Tomorrow has a way of coming.
Suppose the escalator slows, and conservative assumptions about life expectancy prevail. In a 2009 study, Olshansky projected future demographics under the hit a wall scenario. The number of Americans 65 or older, 43 million today, could reach 108 million in 2050that would be like adding three more Floridas, inhabited entirely by seniors. The oldest old cohort, those 85 and older, may increase at least fivefold, to more than 6 percent of the U.S. citizenry. Olshansky projected that by 2050, life expectancy will extend three to eight years past the age used by the Social Security Administration to assess the solvency of its system, while forecasting that by 2050, Medicare and Social Security will rack up between $3.2 trillion and $8.3 trillion in unfunded obligations. (State and local governments have at least another $1 trillion in unfunded pension liabilities.) These disconcerting numbers flow from the leading analyst who thinks that the life-span increase is slowing down.
When President Obama took office, Social Securitys trustees said the current benefits structure was funded until 2037. Now the Congressional Budget Office says the year of reckoning may come as soon as 2031. States may be funding their pension obligations using fuzzy math: New York issues promissory notes; Illinois and New Jersey sell debt instruments distressingly similar to junk bonds. Many private pension plans are underfunded, and the Pension Benefit Guaranty Corporation, which on paper appears to insure them, is an accident looking for a place to happen. Twice in the past three years, Congress has voted to allow corporations to delay contributions to pension plans. This causes them to pay more taxes in the present year, giving Congress more to spend, while amplifying problems down the road. Social Securitys disability fund may fail as soon as late 2016. Medicare spending is rising faster than Social Security spending, and is harder to predict. Projections show the main component of Medicare, its hospital fund, failing by 2030.
The Congressional Budget Office estimates that over the next decade, all federal spending growth will come from entitlementsmainly Social Security and Medicareand from interest on the national debt. The nonpartisan think tank Third Way has calculated that at the beginning of the Kennedy presidency, the federal government spent $2.50 on public investmentsinfrastructure, education, and researchfor every $1 it spent on entitlements. By 2022, Third Way predicts, the government will spend $5 on entitlements for every $1 on public investments. Infrastructure, education, and research lead to economic growth; entitlement subsidies merely allow the nation to tread water.
If health span can be improved, the costs of aging-related disability may be manageable. Not that long ago, vast sums were spent on iron lungs and sanitariums for treatment of polio: preventing the disease has proved much less expensive than treating it. If chronic ailments related to aging can be prevented or significantly delayed, big-ticket line items in Medicare might not go off the rails.
But if health span does not improve, longer life could make disability in aging an economic crisis. Today, Medicare and Medicaid spend about $150 billion annually on Alzheimers patients. Absent progress against aging, the number of people with Alzheimers could treble by 2050, with society paying as much for Alzheimers care as for the current defense budget.
Many disabilities associated with advanced years cannot be addressed with pharmaceuticals or high-tech procedures; caregivers are required. Providing personal care for an aged invalid is a task few wish to undertake. Already many lists of careers with the most job openings are headed by caregiver or nurses aide, professions in which turnover is high.
As longevity increases, so too does the number of living grandparents. Families that once might have had one oldest old relative find themselves with three or four, all expecting care or money. At the same time, traditional family trees are being replaced with diagrams that resemble maps of the London Underground. Will children of blended families feel the same obligation to care for aging stepparents as they feel for biological parents? Just the entry of the phrase birth parent into the national lexicon suggests the magnitude of the change.
With Japan at the leading edge of lengthening life expectancy, its interest in robotics can be eerie. Foxconn, the Asian electronics giant, is manufacturing for the Japanese market a creepy mechanized thing named Pepper that is intended to provide company for the elderly. More-sophisticated devices may be in store. A future in which large numbers of very old, incapacitated people stare into the distance as robot attendants click and hum would be a bad science-fiction movie if it didnt stand a serious chance of happening.
As the population ages, so do the political powers that beand theyre aging in place. Computerized block-by-block voting analysis and shameless gerrymanderingMarylands new sixth congressional district is such a strange shape, it would have embarrassed Elbridge Gerrylock incumbents into power as never before. Campaign-finance laws appear to promote reform, but in fact have been rigged to discourage challengers. Between rising life expectancy and the mounting power of incumbency, both houses of Congress are the oldest theyve ever been: the average senator is 62 years old; the average representative, 57.
A graying Congress would be expected to be concerned foremost with protection of the status quo. Government may grow sclerotic at the very time the aging of the populace demands new ideas. Theres already a tremendous advantage to incumbency, one experienced political operative told me. As people live longer, incumbents will become more entrenched. Strom Thurmond might not be unusual anymore. Many from both parties could cling to power too long, freezing out fresh thinking. It wont be good for democracy. The speaker was no starry-eyed radical: he was Karl Rove.
Now think of the Supreme Court as life expectancy increases. The nine justices on the first Court sat an average of nine years; the last nine to depart, an average of 27 years. John Paul Stevens, the most recent to retire, was a justice for 35 years. If Clarence Thomas lives to the actuarial life expectancy of a male his current age, he could be a Supreme Court justice for 40 years.
The Framers would be aghast at the idea of a small cadre of unelected potentates lording it over the body politic for decades. When the Constitution was written, no one could have anticipated how much life span would increase, nor how much power the Supreme Court would accrue. If democracy is to remain vibrant as society ages, campaign laws must change to help challengers stand a chance versus incumbents, and the Constitution must be amended to impose a term limit on the Supreme Court, so confirmation as a justice stops being a lifetime appointment to royalty.
In 1940, the typical American who reached age 65 would ultimately spend about 17 percent of his or her life retired. Now the figure is 22 percent, and still rising. Yet Social Security remains structured as if longevity were stuck in a previous century. The early-retirement option, added by Congress in 1961start drawing at age 62, though with lower benefitsis appealing if life is short, but backfires as life span extends. People who opt for early Social Security may reach their 80s having burned through savings, and face years of living on a small amount rather than the full benefit they might have received. Polls show that Americans consistently underestimate how long they will livea convenient assumption that justifies retiring early and spending now, while causing dependency over the long run.
James Vaupel has warned that refusing to acknowledge longevitys steady march distorts peoples decisions about how much to save and when to retire and gives license to politicians to postpone painful adjustments to Social Security. Ronald Reagan was the last president to push through legislation to account for life-span changes. His administration increased the future eligible age of full Social Security benefits from 65 to 66 or 67, depending on ones birth year. Perhaps 99 percent of members of Congress would agree in private that retirement economics must change; none will touch this third rail. Generating more Social Security revenue by lifting the payroll-tax cap, currently $117,000, is the sole politically attractive option, because only the well-to-do would be impacted. But the Congressional Budget Office recently concluded that even this soak-the-rich option is insufficient to prevent insolvency for Social Security. At least one other change, such as later retirement or revised cost-of-living formulas, is required. A fair guess is that the government will do nothing about Social Security reform until a crisis strikesand then make panicked, ill-considered moves that foresight might have avoided.
Americans may decry government gridlock, but they cant blame anyone else for their own decisions. Peoples retirement savings simply must increase, though this means financial self-discipline, which Americans are not known for. Beyond that, most individuals will likely need to take a new view of what retirement should be: not a toggle switchno work at all, after years of full-time laborbut a continuum on which a person gradually downshifts to half-time, then to working now and then. Lets call it the retirement track rather than retirement: a phase of continuing to earn and save as full-time work winds down.
Widespread adoption of a retirement track would necessitate changes in public policy and in employers attitudes. Banks dont think in terms of smallish loans to help a person in the second half of life start a home-based business, but such lending might be vital to a graying population. Many employers are required to continue offering health insurance to those who stay on the job past 65, even though they are eligible for Medicare. Employers premiums for these workers are much higher than for young workers, which means employers may have a logical reason to want anyone past 65 off the payroll. Ending this requirement would make seniors more attractive to employers.
Many people may find continuing to work but under the lower-stress circumstances of part-time employment to be preferable to a gold watch, then idleness. Gradual downshifting could help ease aging people into volunteer service roles, where theres never any end of things to do. The retirement track could be more appealing than traditional retirement. A longer health span will be essential to making it possible.
Understanding the evolutionary biology of aging might help the quest for improved health span. Each cell of the body contains DNA code for a fresh, healthy cell, yet that blueprint is not called on as we grow old. Evolutionists including Alfred Russel Wallace have toyed with the idea of programmed deaththe notion that natural selection wants old animals to die in order to free up resources for younger animals, which may carry evolved genetic structures. Current thinking tends to hold that rather than trying to make older animals die, natural selection simply has no mechanism to reward longevity.
Felipe Sierra, a researcher at the National Institute on Aging, says, Evolution doesnt care about you past your reproductive age. It doesnt want you either to live longer or to die, it just doesnt care. From the standpoint of natural selection, an animal that has finished reproducing and performed the initial stage of raising young might as well be eaten by something, since any favorable genetic quality that expresses later in life cannot be passed along. Because a mutation that favors long life cannot make an animal more likely to succeed at reproducing, selection pressure works only on the young.
A generation ago, theorists suspected that menopause was an evolutionary adaptation exclusive to the Homo genuswomen stop expending energy to bear children so they can care longer for those already born, as mothers and grandmothers. This, the theory goes, increases childrens chances of survival, allowing them to pass along family genes. Yet recent research has shown that animals including lions and baboons also go through menopause, which increasingly looks more like a malfunction of aging cells than a quality brought about by selection pressure. As for the idea that grandparents help their grandchildren prosper, favoring longevitythe grandmother effectthis notion, too, has fared poorly in research.
The key point is: if nothing that happens after a person reproduces bears on which genes flourish, then nature has never selected for qualities that extend longevity. Evolution favors strength, intelligence, reflexes, sexual appeal; it does not favor keeping an organism running a long time. For example, a growing body needs calcium, so nature selected for the ability to metabolize this element. In later life, calcium causes stiffening of the arteries, a problem that evolution has no mechanism to correct, since hardened arteries do not occur until its too late for natural selection to side with any beneficial mutation. Testosterone is essential to a youthful man; in an aging man, it can be a factor in prostate cancer. Evolution never selected for a defense against that.
Similar examples abound; the most important may be senescent cells. Natural selection probably favors traits that reduce the risk of cancer, because cancer can strike the young before reproductive age is reached. Senescence doesnt occur until evolution is no longer in play, so natural selection has left all mammal bodies with a defect that leads to aging and death.
If senescence could be slowed, men and women hardly would become immortal. Violence, accidents, and contagious disease still would kill. Even if freed of chronic conditions, eventually our bodies would fail.
But it is not credulous futurism to suppose that drugs or even genetic therapy may alter the human body in ways that extend longevity. Brian Kennedy, of the Buck Institute, notes, Because natural selection did not improve us for aging, theres a chance for rapid gains. The latest BMWs are close to perfect. How can an engineer improve on them? But the Model T would be easy to improve on now. When young, genetically we are BMWs. In aging, we become Model Ts. The evolutionary improvements havent started yet.
In the wild, young animals outnumber the old; humanity is moving toward a society where the elderly outnumber the recently arrived. Such a world will differ from todays in many outward aspects. Warm-weather locations are likely to grow even more popular, though with climate change, warm-weather locations may come to include Buffalo, New York. Ratings for football, which is loud and aggressive, may wane, while baseball and theatergoing enjoy a renaissance. The shift back toward cities, initiated by the educated young, may give way to another car-centric suburban and exurban growth phase.
The university, a significant aspect of the contemporary economy, centuries ago was a place where the fresh-faced would be prepared for a short life; today the university is a place where adults watch children and grandchildren walk to Pomp and Circumstance. The university of the future may be one that serves all ages. Colleges will reposition themselves economically as offering just as much to the aging as to the adolescent: courses priced individually for later-life knowledge seekers; lots of campus events of interest to students, parents, and the community as a whole; a pleasant college-town atmosphere to retire near. In decades to come, college professors may address students ranging from age 18 to 80.
Products marketed to senior citizens are already a major presence on television, especially during newscasts and weathercasts. Advertising pitched to the elderly may come to dominate the airwaves, assuming there still is television. But consumerism might decline. Neurological studies of healthy aging people show that the parts of the brain associated with reward-seeking light up less as time goes on. Whether its hot new fashions or hot-fudge sundaes, older people on the whole dont desire acquisitions as much as the young and middle-aged do. Denounced for generations by writers and clergy, wretched excess has repelled all assaults. Longer life spans may at last be the counterweight to materialism.
If health span extends, the nuclear family might be seen as less central. Bearing and raising children would no longer be the all-consuming life event.
Deeper changes may be in store as well. People in their late teens to late 20s are far more likely to commit crimes than people of other ages; as society grays, the decline of crime should continue. Violence in all guises should continue downward, too. Horrible headlines from Afghanistan or Syria are exceptions to an overall trend toward less warfare and less low-intensity conflict. As Steven Pinker showed in the 2011 book Better Angels of Our Nature, total casualties of combat, including indirect casualties from the economic harm associated with fighting, have been declining, even as the global population has risen. In 1950, one person in 5,000 worldwide died owing to combat; by 2010, this measure was down to one person in 300,000. In recent years, far more people have been killed by car crashes than by battle. Simultaneously, per capita military expenditure has shrunk. My favorite statistic about the world: the Stockholm International Peace Research Institute reports that, adjusting to todays dollars, global per capita military spending has declined by one-third in the past quarter century.
The end of the Cold War, and the proxy conflicts it spawned, is an obvious influence on the subsiding of warfare, as is economic interconnectedness. But aging may also be a factor. Counterculture optics notwithstanding, polls showed that the young were more likely to support the Vietnam War than the old were; the young were more likely to support the 2003 invasion of Iraq, too. Research by John Mueller, a political scientist at Ohio State University, suggests that as people age, they become less enthusiastic about war. Perhaps this is because older people tend to be wiser than the youngand couldnt the world use more wisdom?
Older people also report, to pollsters and psychologists, a greater sense of well-being than the young and middle-aged do. By the latter phases of life, material and romantic desires have been attained or given up on; passions have cooled; and for most, a rich store of memories has been compiled. Among the core contentions of the well-being research of the Princeton University psychologist Daniel Kahneman is that in the end, memories are all you keepwhats in the mind matters more than what you own. Regardless of net worth, the old are well off in this sense.
Should large numbers of people enjoy longer lives in decent health, the overall well-being of the human family may rise substantially. In As You Like It, Jaques declares, Man in his time plays many parts, his acts being seven ages. The first five embody promise and powerinfant, schoolboy, lover, soldier, and success. The late phases are entirely negativepantaloon, a period as the butt of jokes for looking old and becoming impotent; then second childishness, a descent into senile dependency. As life expectancy and health span increase, the seven ages may demand revision, with the late phases of life seen as a positive experience of culmination and contentment.
Further along may be a rethinking of life as better structured around friendship than around family, the basic unit of human society since the mists of prehistory. In the brief life of previous centuries, all a man or woman could hope to accomplish was to bear and raise children; enervation followed. Today, life is longer, but an education-based economy requires greater investments in childrencontemporary parents are still assisting offspring well into a childs 20s. As before, when the child-rearing finally is done, decline commences.
But if health span extends, the nuclear family might be seen as less central. For most people, bearing and raising children would no longer be the all-consuming life event. After child-rearing, a phase of decades of friendships could awaitpotentially more fulfilling than the emotionally charged but fast-burning bonds of youth. A change such as this might have greater ramifications for society than changes in work schedules or health-care economics.
Regardless of where increasing life expectancy leads, the direction will be into the unknownfor society and for the natural world. Felipe Sierra, the researcher at the National Institute on Aging, puts it this way: The human ethical belief that death should be postponed as long as possible does not exist in naturefrom which we are now, in any case, diverging.
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What Happens When We All Live to 100? - The Atlantic
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Stem Cell 100 Longevity Telomere Support Supplement SC100 …
Posted: at 6:31 am
Stem Cell 100 is designed to rejuvenate your body and slow the aging process to help you feel and function more like a young person. This can help you feel better, look younger and improve your health.
Most of the cells in your body lose function with age. Everyone has special cells called adult stem cells which are needed to repair damaged and old tissues, but adult stem cells themselves are also aging.
Until now there was not much you could do about it. Stem Cell 100 rejuvenates adult stem cells and their micro-environments with the proprietary SC100 formula. Stem Cell 100+ is a more powerful and faster acting version of the same nutraceutical.
Developed by experts in the anti-aging field, patent-pending Stem Cell 100 is the only supplement proven to double maximum lifespan of an animal model. No other product or therapy including caloric restriction even comes close.
Harness the Power of Your Own Stem Cells
Millions of people suffer from chronic conditions of aging and disease. Based on international scientific studies in many academic and industry laboratories, there is new hope that many of the conditions afflicting mankind can some day be cured or greatly improved using stem cell regenerative medicine.
Stem Cell 100 offers a way to receive some of the benefits of stem cell therapy today by improving the effectiveness of your own adult stem cells.
Stem Cell 100 Helps to Support:
The statements above have not been reviewed by the FDA. Stem Cell 100 is not a preventive or treatment for any disease.
Help Rejuvenate Your Body by Boosting Your Own Stem Cells
As a child, we are protected from the ravages of aging and can rapidly recover from injury or illness because of the ability of the young regenerative stem cells of children have a superior ability to repair and regenerate most damaged tissues.
As we age, our stem cell populations become depleted and/or slowly lose their capacity to repair. Moreover, the micro-environment (i.e. niches) around stem cells becomes less nurturing with age, so cell turnover and repair are further reduced. This natural progression occurs so slowly that we are barely aware of it, but we start to notice the body changes in our 20s, 30s, 40s, and especially after 50 years of age.
Stem Cell 100 helps adults regain their youthful regenerative potential by stabilizing stem cell function.
Stem Cell 100 works differently than other stem cell products on the market
You may have seen a number of products that are advertised as stimulating or enhancing the number of stem cells. Each person only has a limited number of stem cells so using them up faster may not be a good strategy. Stem Cell 100 is about improving the effectiveness and longevity of your stem cells as well as preserving the stem cell micro-environment. That should be the goal of any effective stem cell therapy and is what Stem Cell 100 is designed to do and what other stem cell products cannot do.
Stem Cell 100 Extends Drosophila (Fruit Fly) Lifespan
In extensive laboratory testing Stem Cell 100 greatly extended both the average and maximum lifespan of Drosophila fruit flies. The study (see Charts below) included three cages of Drosophila fruit flies that were treated with Stem Cell 100 (Cages T1 to T3) and three cages which were untreated controls (Cages C1 to C3). Each cage started with 500 fruit flies including 250 males and 250 females.
The experiment showed that median lifespan more than doubled with a 123% increase.
While fruit flies are not people they are more like us than you might think. Drosophila have a heart and circulatory system, and the most common cause of death is heart failure. Like humans and other mammals (e.g. mice), it is difficult to increase their lifespan significantly.
These observed results outperform every lifespan enhancing treatment ever tested including experiments using genetic modification and dietary restriction.
The longest living fruit fly receiving Stem Cell 100 lived 89 days compared to the longest living untreated control which lived 48 days. It is possible that the single longest living fruit fly lived longer for other reasons such as genetic mutation, however, there were many others that lived almost as long so it was not just an aberation.
The oldest 5% of the treated fruit flies lived 77% longer than the oldest 5% of the control group. It is also important that the study showed an improved ability of the fruit flies to survive stress and illness at all ages not just during old age. Even after the first few days of the study there were already more of the
Stem Cell 100 treated fruit flies alive that survived youth than the control group of untreated fruit flies. For additional information about the study please go to our Longevity page.
SK, Santa Fe, New Mexico
I have been using Stem Cell 100 for about one year. Initially I noticed a boost in energy level, which now remains steady-hence not noticed I have experienced no adverse effects from taking this product. I heartily recommend Stem Cell 100 and plan to continue on it.*
Leslie
Stem Cell 100 has made a noticeable difference in me, including turning my gray hair back to its original color, which supposedly is impossible. The reversal of the gray hair to original color began a couple of months after starting the pill. After about 10 months, the gray hair is mostly gone. At the current rate of improvement, I expect my hair to completely be back to its original color within 1 to 2 months. I think my beard will take longer, but it was the first to gray.
Also, my skin became smoother and younger looking. The skin and hair rely heavily on stem cells, and they seem to benefit strongly from this product. Im so excited about telling people my results because there is nothing that can reverse the graying of hair. It will give me evidence that this supplement thing is really powerful.
Unfortunately, I dont have before and after pictures because I didnt read any claims that the product would affect hair color. I would just say that Im a person who totally believes that it does me no good to imagine things or interpret tings in a way favorable to what I want to believe. When Im convinced enough to make a statement, you can count on it.*
Joey, California
I am a 48 year old working woman. A friend of mine introduced me to Stem Cell 100. After taking Stem Cell 100 for about 4 months my anxiety level has really been diminished. Its a great supplement and I would recommend it to everyone!*
Paul, California
I am an active 61 year old man in excellent health, but had experienced a serious drop in my energy level at the time I enrolled in a 4-month trial of Stem Cell 100. Within a month, my energy increased noticeably and I began to take to my physical activities (running, cycling) with a renewed enthusiasm and intensity level. My mood began to elevate steadily, and soon I had even lost those few stubborn pounds that had eluded me for years. I am very enthusiastic about Stem Cell 100. I look forward to continuing with the new, improved formulation, and would not hesitate to recommend it.*
Mike, Texas
After taking the Stem Cell 100 for the last month my sinuses have also cleared, unplugging my ears for the first time since mid September.*
Tom, Australia
Only after about 2-3 weeks of taking Stem Cell 100 my eye sight returned back to a level where I did not need glasses to work on my computer monitors. My eyes had always been good but had started to deteriorate about a year ago where 50% of the time I had to wear my glasses. I was shocked to find the improvement so quick. I found I was less stressed. No other changes to lifestyle yet a measureable difference.
My fingers would sometimes get stiff in the mornings after long days on the keyboard. This stiffness disappeared. Some of my hair is getting darker. I have a full body of hair that had virtually all turned grey but I noticed that some of my hair was starting regrow brown my original colour. I had some age spots in my left leg that are disappearing. Generally, I feel great.*
Willie, California
As I was sprinting this morning around 6:00am I noticed that I was not hurting anymore! I have been having sore knees, ankles, hamstrings and back for the last couple of years. I usually just ran through it, but I noticed since I have been taking the Stem Cell 100 capsules for about 45 days now, those nagging pains are gone away!*
*DIsclaimer: The testimonials reflect the real life experiences written and voluntarily submitted to us by individuals who used our products. Individual results may vary. We do not claim that any individual experience recounted is typical or representative of what any other consumer might experience.
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Supplement Facts
Stem Cell 100 and Stem Cell 100+ are Patent-Pending Life Code Nutraceuticals.
All Life Code products arenutraceutical grade and provide the best of science along with the balance of nature. Stem Cell 100 is vegetarian.
Serving Size: One type O capsule
Servings Per Container: 60 Capsules
Recommended Use: Typical usage of Stem Cell 100 is two capsules per day, preferably at meal times. While both capsules can be taken at the same time, it is preferable to separate the two capsules by at least 4 hours. Since Stem Cell 100 is a potent formulation, do not take more than three capsules per day. One capsule per day may be sufficient for those below 110 pounds.
Recommended Users: Anyone from ages 22 and up could benefit from Stem Cell 100 or Stem Cell 100+. Those in their 20s and 30s will like the boost in endurance during sports or exercise, while older users will notice better energy and general health with the potential for some weight loss.
Stem Cell 100 was our first multi-pathway longevity nutraceutical. Stem Cell 100+ is a more advanced, faster acting and powerful version of Stem Cell 100.
Click label to enlarge
Active Stem Cell 100 Ingredients: There are ten herbal components that make up the patent-pending combination in Stem Cell 100. The herbal components are highly extracted natural herbs that are standardized for active components that promote adult stem cells and lower inflammation:
1) Polysaccharides, flavonoids, and astragalosides extracted from Astragalus membranaceus, which has many positive effects on stem cells and the cardiovascular and immune systems.
2) Proprietary natural bilberry flavonoids and other compounds from a stabilized nutraceutical grade medicinal Vaccinium extract. Activate metabolic PPARS and helps produce healthy levels of cholesterol and inflammation. Also has anti-fungal and anti-viral activity.
3) Flavonoids and oligo-proanthocyanidins (OPCs) extracted from Pine Bark, which greatly reduce oxidative stress, DNA damage, and inflammation.
4) L-Theanine, which is a natural amino acid from Camellia sinesis that reduces mental stress and inflammation while improving cognition and protecting brain cells from ischemic or toxic injury.
5) Pterocarpus Marsupium, which contains two stable resveratrol analogs which promote stem cells, lower inflammation, and stabilized metabolism.
6) Polygonum Multiflorium stem stem is a popular Chinese herbal tonic that fights premature aging and promotes youthfulness. Polygonum is reported to enhance fertility by improving sperm count in men and egg vitality in women. Polygonum is also widely used in Asia to strengthen muscle and is thus used by many athletes as an essential tonic for providing strength and stamina to the body.
Modern research has supported Polygonum multiflorium stem in that animal studies have proven that it can extend lifespan and improve the quality of life. Polygonum appears to protect the liver and brain against damage, perhaps by improving immune and cardiovascular health. The stem sections of Polygonum multiflorium are also calming to the nervous system and promote sounder sleep. Life Code uses a proprietary Polygonum multiflorium stem extract.
7) Schisandra Berry is used by many Chinese women to preserve their youthful beauty. For thousands of years, Schisandra has been prized as an antiaging tonic that increases stamina and mental clarity, while fighting stress and fatigue. In Chinese traditional medicine, Schisandra berry has been used for liver disorders and to enhance resistance to infection and promote skin health and better sleep.
Schisandra berry is classified as an adaptogen, which can stimulate the central nervous system, increase brain efficiency, improve reflexes, and enhance endurance. Modern research indicates that Schisandra berry extracts have a protective effect on the liver and promote immunity. A double-blind human trial suggested that Schisandra berry may help patients with viral hepatitis, which is very prevalent in China.
Recent work indicates that the liver is protected by the enhanced production of glutathione peroxidase, which helps detoxify the liver. Life Code uses a proprietary Schisandra berry extract.
8) Fo-Ti Root (aka He-Shou-Wu) is one of the most widely used Chinese herbal medicines to restore blood, kidney, liver, and cardiovascular health. Fo-Ti is claimed to have powerful rejuvenating effects on the brain, endocrine glands, the immune system, and sexual vigor.
Legend has it that Professor Li Chung Yun took daily doses of Fo-Ti to live to be 256 and is said to have outlived 23 wives and spawned 11 generations of descendents before his death in 1933. While it is unlikely that he really lived to such an old age there is scientific support for Fo-Ti as beneficial for health and longevity.
Like the Indian Keno bark, Fo-ti contains resveratrol analogs and likely acts by various mechanism, which includes liver detoxification and protection of skin from UVB radiation. Life Code uses a proprietary Fo-Ti root extract.
9) Camellia sinensis has many bioactive polyphenols including the potent epigallocatechin-3-gallate (EGCG). A 2006 Japanese study published in the Journal of the American Medical Association reports that adults aged 40 to 79 years of age who drank an average of 5 or more cups of tea per day had a significantly lower risk of dying from all causes (23% lower for females and 12% lower for males). The study tracked more than 40,000 adults for up to 11 years and found dramatically lower rates of cardiovascular disease and strokes in those drinking 5 or more cups of tea.
Many studies have found that adults drinking 3 or more cups of tea per day have significantly less cancer. Other studies have found that green tea helps protect against age-related cognitive decline, kidney disease, periodontal disease, and type 2 diabetes. Green tea also promotes visceral fat loss and higher endurance levels.
Summarizing all of the thousands of studies on tea and tea polyphenols that have been published, it can be concluded that tea polyphenols preserve health and youth. This conclusion is backed up by gene studies showing that tea polyphenols decrease insulin-like growth factor-1 (IGF-1), which is a highly conserved genetic pathway that has been strongly linked to aging in yeast, worms, mice, and humans. If everyone could drink 4 to 5 cups of green tea each day, they could enjoy these important health benefits, but for most people drinking that much green tea can disturb their sleep patterns.
Life Code uses a nutraceutical grade green tea extract that has 98% polyphenols and 50% ESCG that provides the polyphenol and ESCG equivalent of 4 to 5 cups of green tea with only 2% of the caffeine. Thus, most or all of the benefits of green tea are provided without concerns about disturbing sleep.
10) Drynaria Rhizome is used extensively in traditional Chinese medicine as an effective herb for healing bones, ligaments, tendons, and lower back problems. Eastern martial art practitioners have used Drynaria for thousands of years to help in recovering from sprains, bruises, and stress fractures.
Drynaria has also helped in many cases of bleeding gums and tinnitus (ringing in the ears). The active components of Drynaria protect bone forming cells by enhancing calcium absorption and other mechanisms. Drynaria is also reported to act as a kidney tonic and to promote hair growth and wound healing. Life Code uses a proprietary Drynaria rhizome extract.
Safety: The extracts in both versions of Stem Cell 100 are pharmaceutical grade and have been individually tested in both animals and humans without significant safety issues. Those with pre-existing conditions of diabetes or hypertension should coordinate this product with your doctor, as lower blood glucose or reduced blood pressure can result from taking the recommended dose of this product.
Warnings: may lower glucose and/or blood pressure in some individuals. The supplement is not recommended for pregnant, lactating, or hypoglycemic individuals.
References
1. Yu, Q., Y.S. Bai, and J. Lin, [Effect of astragalus injection combined with mesenchymal stem cells transplantation for repairing the Spinal cord injury in rats]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2010. 30(4): p. 393-7.
2. Xu, C.J., et al., [Effect of astragalus polysaccharides on the proliferation and ultrastructure of dog bone marrow stem cells induced into osteoblasts in vitro]. Hua Xi Kou Qiang Yi Xue Za Zhi, 2007. 25(5): p. 432-6.
3. Xu, C.J., et al., [Effects of astragalus polysaccharides-chitosan/polylactic acid scaffolds and bone marrow stem cells on repairing supra-alveolar periodontal defects in dogs]. Zhong Nan Da Xue Xue Bao Yi Xue Ban, 2006. 31(4): p. 512-7.
4. Zhu, X. and B. Zhu, [Effect of Astragalus membranaceus injection on megakaryocyte hematopoiesis in anemic mice]. Hua Xi Yi Ke Da Xue Xue Bao, 2001. 32(4): p. 590-2.
5. Qiu, L.H., X.J. Xie, and B.Q. Zhang, Astragaloside IV improves homocysteine-induced acute phase endothelial dysfunction via antioxidation. Biol Pharm Bull, 2010. 33(4): p. 641-6.
6. Araghi-Niknam, M., et al., Pine bark extract reduces platelet aggregation. Integr Med, 2000. 2(2): p. 73-77.
7. Rohdewald, P., A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology. Int J Clin Pharmacol Ther, 2002. 40(4): p. 158-68.
8. Koch, R., Comparative study of Venostasin and Pycnogenol in chronic venous insufficiency. Phytother Res, 2002. 16 Suppl 1: p. S1-5.
9. Rimando, A.M., et al., Pterostilbene, a new agonist for the peroxisome proliferator-activated receptor alpha-isoform, lowers plasma lipoproteins and cholesterol in hypercholesterolemic hamsters. J Agric Food Chem, 2005. 53(9): p. 3403-7.
10. Manickam, M., et al., Antihyperglycemic activity of phenolics from Pterocarpus marsupium. J Nat Prod, 1997. 60(6): p. 609-10.
11. Grover, J.K., V. Vats, and S.S. Yadav, Pterocarpus marsupium extract (Vijayasar) prevented the alteration in metabolic patterns induced in the normal rat by feeding an adequate diet containing fructose as sole carbohydrate. Diabetes Obes Metab, 2005. 7(4): p. 414-20.
12. Mao, X.Q., et al., Astragalus polysaccharide reduces hepatic endoplasmic reticulum stress and restores glucose homeostasis in a diabetic KKAy mouse model. Acta Pharmacol Sin, 2007. 28(12): p. 1947-56.
13. Schafer, A. and P. Hogger, Oligomeric procyanidins of French maritime pine bark extract (Pycnogenol) effectively inhibit alpha-glucosidase. Diabetes Res Clin Pract, 2007. 77(1): p. 41-6.
14. Kwak, C.J., et al., Antihypertensive effect of French maritime pine bark extract (Flavangenol): possible involvement of endothelial nitric oxide-dependent vasorelaxation. J Hypertens, 2009. 27(1): p. 92-101.
15. Xue, B., et al., Effect of total flavonoid fraction of Astragalus complanatus R.Brown on angiotensin II-induced portal-vein contraction in hypertensive rats. Phytomedicine, 2008.
16. Mizuno, C.S., et al., Design, synthesis, biological evaluation and docking studies of pterostilbene analogs inside PPARalpha. Bioorg Med Chem, 2008. 16(7): p. 3800-8.
17. Sato, M., et al., Dietary pine bark extract reduces atherosclerotic lesion development in male ApoE-deficient mice by lowering the serum cholesterol level. Biosci Biotechnol Biochem, 2009. 73(6): p. 1314-7.
18. Kimura, Y. and M. Sumiyoshi, French Maritime Pine Bark (Pinus maritima Lam.) Extract (Flavangenol) Prevents Chronic UVB Radiation-induced Skin Damage and Carcinogenesis in Melanin-possessing Hairless Mice. Photochem Photobiol, 2010.
19. Pavlou, P., et al., In-vivo data on the influence of tobacco smoke and UV light on murine skin. Toxicol Ind Health, 2009. 25(4-5): p. 231-9.
20. Ni, Z., Y. Mu, and O. Gulati, Treatment of melasma with Pycnogenol. Phytother Res, 2002. 16(6): p. 567-71.
21. Bito, T., et al., Pine bark extract pycnogenol downregulates IFN-gamma-induced adhesion of T cells to human keratinocytes by inhibiting inducible ICAM-1 expression. Free Radic Biol Med, 2000. 28(2): p. 219-27.
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Stem Cell 100 Longevity Telomere Support Supplement SC100 ...
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Happiness – Wikipedia, the free encyclopedia
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Happiness is a mental or emotional state of well-being defined by positive or pleasant emotions ranging from contentment to intense joy.[1] Happy mental states may also reflect judgements by a person about their overall well-being.[2] A variety of biological, psychological, economic, religious and philosophical approaches have striven to define happiness and identify its sources. Various research groups, including positive psychology and happiness economics are employing the scientific method to research questions about what "happiness" is, and how it might be attained.
The United Nations declared 20 March the International Day of Happiness to recognise the relevance of happiness and well-being as universal goals.
Philosophers and religious thinkers often define happiness in terms of living a good life, or flourishing, rather than simply as an emotion. Happiness in this sense was used to translate the Greek Eudaimonia, and is still used in virtue ethics. There has been a transition over time from emphasis on the happiness of virtue to the virtue of happiness.[3] Since the turn of the millennium, the human flourishing approach, advanced particularly by Amartya Sen has attracted increasing interest in psychological, especially prominent in the work of Martin Seligman, Ed Diener and Ruut Veenhoven, and international development and medical research in the work of Paul Anand.[citation needed]
A widely discussed political value expressed in the United States Declaration of Independence of 1776, written by Thomas Jefferson, is the universal right to "the pursuit of happiness."[4] This suggests a subjective interpretation but one that nonetheless goes beyond emotions alone.[citation needed]
Happiness is a fuzzy concept and can mean many different things to many people. Part of the challenge of a science of happiness is to identify different concepts of happiness, and where applicable, split them into their components. Related concepts are well-being, quality of life and flourishing. At least one author defines happiness as contentment.[5] Some commentators focus on the difference between the hedonistic tradition of seeking pleasant and avoiding unpleasant experiences, and the eudaimonic tradition of living life in a full and deeply satisfying way.[6]
The 2012 World Happiness Report stated that in subjective well-being measures, the primary distinction is between cognitive life evaluations and emotional reports.[7] Happiness is used in both life evaluation, as in How happy are you with your life as a whole?, and in emotional reports, as in How happy are you now?, and people seem able to use happiness as appropriate in these verbal contexts. Using these measures, the World Happiness Report identifies the countries with the highest levels of happiness.[citation needed]
Since the 1960s, happiness research has been conducted in a wide variety of scientific disciplines, including gerontology, social psychology, clinical and medical research and happiness economics. During the past two decades, however, the field of happiness studies has expanded drastically in terms of scientific publications, and has produced many different views on causes of happiness, and on factors that correlate with happiness,[8] but no validated method has been found to substantially improve long-term happiness in a meaningful way for most people.
Sonja Lyubomirsky concludes in her book The How of Happiness that 50 percent of a given human's happiness level is genetically determined (based on twin studies), 10 percent is affected by life circumstances and situation, and a remaining 40 percent of happiness is subject to self-control.[citation needed]
The results of the 75-year Grant Study of Harvard undergraduates show a high correlation of loving relationship, especially with parents, with later life wellbeing.[9]
In the 2nd Edition of the Handbook of Emotions (2000), evolutionary psychologists Leda Cosmides and John Tooby say that happiness comes from "encountering unexpected positive events". In the 3rd Edition of the Handbook of Emotions (2008), Michael Lewis says "happiness can be elicited by seeing a significant other". According to Mark Leary, as reported in a November 1995 issue of Psychology Today, "we are happiest when basking in the acceptance and praise of others". Sara Algoe and Jonathan Haidt say that "happiness" may be the label for a family of related emotional states, such as joy, amusement, satisfaction, gratification, euphoria, and triumph.[10]
It has been argued that money cannot effectively "buy" much happiness unless it is used in certain ways.[11] "Beyond the point at which people have enough to comfortably feed, clothe, and house themselves, having more money - even a lot more money - makes them only a little bit happier."[according to whom?] A Harvard Business School study found that "spending money on others actually makes us happier than spending it on ourselves".[12]
Meditation has been found to lead to high activity in the brain's left prefrontal cortex, which in turn has been found to correlate with happiness.[13]
Psychologist Martin Seligman asserts that happiness is not solely derived from external, momentary pleasures,[14] and provides the acronym PERMA to summarize Positive Psychology's correlational findings: humans seem happiest when they have
There have also been some studies of how religion relates to happiness. Causal relationships remain unclear, but more religion is seen in happier people. This correlation may be the result of community membership and not necessarily belief in religion itself. Another component may have to do with ritual.[15]
Abraham Harold Maslow, an American professor of psychology, founded humanistic psychology in the 1930s. A visual aid he created to explain his theory, which he called the hierarchy of needs, is a pyramid depicting the levels of human needs, psychological, and physical. When a human being ascends the steps of the pyramid, he reaches self-actualization. Beyond the routine of needs fulfillment, Maslow envisioned moments of extraordinary experience, known as peak experiences, profound moments of love, understanding, happiness, or rapture, during which a person feels more whole, alive, self-sufficient, and yet a part of the world. This is similar to the flow concept of Mihly Cskszentmihlyi.[citation needed]
Self-determination theory relates intrinsic motivation to three needs: competence, autonomy, and relatedness.
Cross-sectional studies worldwide support a relationship between happiness and fruit and vegetable intake. Those eating fruits and vegetables each day have a higher likelihood of being classified as very happy, suggesting a strong and positive correlation between fruit and vegetable consumption and happiness.[16] Whether it be in South Korea,[17] Iran,[18] Chile,[19] USA,[20] or UK,[21] greater fruit and vegetable consumption had a positive association with greater happiness, independent of factors such as smoking, exercise, body mass index, or socio-economic factors.
Religion and happiness have been studied by a number of researchers, and religion features many elements addressing the components of happiness, as identified by positive psychology. Its association with happiness is facilitated in part by the social connections of organized religion,[22] and by the neuropsychological benefits of prayer[23] and belief.
There are a number of mechanisms through which religion may make a person happier, including social contact and support that result from religious pursuits, the mental activity that comes with optimism and volunteering, learned coping strategies that enhance one's ability to deal with stress, and psychological factors such as "reason for being." It may also be that religious people engage in behaviors related to good health, such as less substance abuse, since the use of psychotropic substances is sometimes considered abuse.[24][25][26][27][28][29]
The Handbook of Religion and Health describes a survey by Feigelman (1992) that examined happiness in Americans who have given up religion, in which it was found that there was little relationship between religious disaffiliation and unhappiness.[30] A survey by Kosmin & Lachman (1993), also cited in this handbook, indicates that people with no religious affiliation appear to be at greater risk for depressive symptoms than those affiliated with a religion.[31] A review of studies by 147 independent investigators found, "the correlation between religiousness and depressive symptoms was -.096, indicating that greater religiousness is mildly associated with fewer symptoms."[32]
The Legatum Prosperity Index reflects the repeated finding of research on the science of happiness that there is a positive link between religious engagement and wellbeing: people who report that God is very important in their lives are on average more satisfied with their lives, after accounting for their income, age and other individual characteristics.[33]
Surveys by Gallup, the National Opinion Research Centre and the Pew Organisation conclude that spiritually committed people are twice as likely to report being "very happy" than the least religiously committed people.[34] An analysis of over 200 social studies contends that "high religiousness predicts a lower risk of depression and drug abuse and fewer suicide attempts, and more reports of satisfaction with sex life and a sense of well-being. However, the links between religion and happiness are always very broad in nature, highly reliant on scripture and small sample number. To that extent there is a much larger connection between religion and suffering (Lincoln 1034)."[32] And a review of 498 studies published in peer-reviewed journals concluded that a large majority of them showed a positive correlation between religious commitment and higher levels of perceived well-being and self-esteem and lower levels of hypertension, depression, and clinical delinquency.[35] A meta-analysis of 34 recent studies published between 1990 and 2001 found that religiosity has a salutary relationship with psychological adjustment, being related to less psychological distress, more life satisfaction, and better self-actualization.[36] Finally, a recent systematic review of 850 research papers on the topic concluded that "the majority of well-conducted studies found that higher levels of religious involvement are positively associated with indicators of psychological well-being (life satisfaction, happiness, positive affect, and higher morale) and with less depression, suicidal thoughts and behaviour, drug/alcohol use/abuse."[37]
However, there remains strong disagreement among scholars about whether the effects of religious observance, particularly attending church or otherwise belonging to religious groups, is due to the spiritual or the social aspectsi.e. those who attend church or belong to similar religious organizations may well be receiving only the effects of the social connections involved. While these benefits are real enough, they may thus be the same one would gain by joining other, secular groups, clubs, or similar organizations.[38]
Terror management theory maintains that people suffer cognitive dissonance (anxiety) when they are reminded of their inevitable death. Through terror management, individuals are motivated to seek consonant elements symbols which make sense of mortality and death in satisfactory ways (i.e. boosting self-esteem).
Research has found that strong belief in religious or secular meaning systems affords psychological security and hope. It is moderates (e.g. agnostics, slightly religious individuals) who likely suffer the most anxiety from their meaning systems. Religious meaning systems are especially adapted to manage death anxiety because they are unlikely to be disconfirmed (for various reasons), they are all encompassing, and they promise literal immortality.[39][40]
Whether emotional effects are beneficial or adverse seems to vary with the nature of the belief. Belief in a benevolent God is associated with lower incidence of general anxiety, social anxiety, paranoia, obsession, and compulsion whereas belief in a punitive God is associated with greater symptoms. (An alternative explanation is that people seek out beliefs that fit their psychological and emotional states.)[41]
Citizens of the world's poorest countries are the most likely to be religious, and researchers suggest this is because of religion's powerful coping abilities.[42][43] Luke Galen also supports terror management theory as a partial explanation of the above findings. Galen describes evidence (including his own research) that the benefits of religion are due to strong convictions and membership in a social group.[44][45][46]
Happiness forms a central theme of Buddhist teachings.[47] For ultimate freedom from suffering, the Noble Eightfold Path leads its practitioner to Nirvana, a state of everlasting peace. Ultimate happiness is only achieved by overcoming craving in all forms. More mundane forms of happiness, such as acquiring wealth and maintaining good friendships, are also recognized as worthy goals for lay people (see sukha). Buddhism also encourages the generation of loving kindness and compassion, the desire for the happiness and welfare of all beings.[48][49][unreliable source?]
Happiness or simcha (Hebrew: ) in Judaism is considered an important element in the service of God.[50] The biblical verse "worship The Lord with gladness; come before him with joyful songs," (Psalm 100:2) stresses joy in the service of God.[citation needed] A popular teaching by Rabbi Nachman of Breslov, a 19th-century Chassidic Rabbi, is "Mitzvah Gedolah Le'hiyot Besimcha Tamid," it is a great mitzvah (commandment) to always be in a state of happiness. When a person is happy they are much more capable of serving God and going about their daily activities than when depressed or upset.[51]
The primary meaning of "happiness" in various European languages involves good fortune, chance or happening. The meaning in Greek philosophy, however, refers primarily to ethics. In Catholicism, the ultimate end of human existence consists in felicity, Latin equivalent to the Greek eudaimonia, or "blessed happiness", described by the 13th-century philosopher-theologian Thomas Aquinas as a Beatific Vision of God's essence in the next life.[52] Human complexities, like reason and cognition, can produce well-being or happiness, but such form is limited and transitory. In temporal life, the contemplation of God, the infinitely Beautiful, is the supreme delight of the will. Beatitudo, or perfect happiness, as complete well-being, is to be attained not in this life, but the next.[53]
While religion is often formalised and community-oriented, spirituality tends to be individually based and not as formalised. In a 2014 study, 320 children, ages 812, in both public and private schools, were given a Spiritual Well-Being Questionnaire assessing the correlation between spirituality and happiness. Spirituality and not religious practices (praying, attending church services) correlated positively with the child's happiness; the more spiritual the child was, the happier the child was. Spirituality accounted for about 326% of the variance in happiness.[54]
The Chinese Confucian thinker Mencius, who 2300 years ago sought to give advice to the ruthless political leaders of the warring states period, was convinced that the mind played a mediating role between the "lesser self" (the physiological self) and the "greater self" (the moral self) and that getting the priorities right between these two would lead to sage-hood. He argued that if we did not feel satisfaction or pleasure in nourishing one's "vital force" with "righteous deeds", that force would shrivel up (Mencius,6A:15 2A:2). More specifically, he mentions the experience of intoxicating joy if one celebrates the practice of the great virtues, especially through music.[55]
Al-Ghazali (10581111) the Muslim Sufi thinker wrote the Alchemy of Happiness, a manual of spiritual instruction throughout the Muslim world and widely practiced today.[citation needed]
The Hindu thinker Patanjali, author of the Yoga Sutras, wrote quite exhaustively on the psychological and ontological roots of bliss.[56]
In the Nicomachean Ethics, written in 350 BCE, Aristotle stated that happiness (also being well and doing well) is the only thing that humans desire for its own sake, unlike riches, honor, health or friendship. He observed that men sought riches, or honor, or health not only for their own sake but also in order to be happy. Note that eudaimonia, the term we translate as "happiness", is for Aristotle an activity rather than an emotion or a state.[57] Thus understood, the happy life is the good life, that is, a life in which a person fulfills human nature in an excellent way. Specifically, Aristotle argues that the good life is the life of excellent rational activity. He arrives at this claim with the Function Argument. Basically, if it's right, every living thing has a function, that which it uniquely does. For humans, Aristotle contends, our function is to reason, since it is that alone that we uniquely do. And performing one's function well, or excellently, is one's good. Thus, the life of excellent rational activity is the happy life. Aristotle does not leave it that, however. For he argues that there is a second best life for those incapable of excellent rational activity.This second best life is the life of moral virtue.[citation needed]
Many ethicists make arguments for how humans should behave, either individually or collectively, based on the resulting happiness of such behavior. Utilitarians, such as John Stuart Mill and Jeremy Bentham, advocated the greatest happiness principle as a guide for ethical behavior.[citation needed]
Friedrich Nietzsche savagely critiqued the English Utilitarians' focus on attaining the greatest happiness, stating "Man does not strive for happiness, only the Englishman does." Nietzsche meant that the making happiness one's ultimate goal, the aim of one's existence "makes one contemptible;" Nietzsche instead yearned for a culture that would set higher, more difficult goals than "mere happiness." Thus Nietzsche introduces the quasi-dystopic figure of the "last man" as a kind of thought experiment against the utilitarians and happiness-seekers; these small, "last men" who seek after only their own pleasure and health, avoiding all danger, exertion, difficulty, challenge, struggle are meant to seem contemptible to Nietzsche's reader. Nietzsche instead wants us to consider the value of what is difficult, what can only be earned through struggle, difficulty, pain and thus to come to see the affirmative value suffering and unhappiness truly play in creating everything of great worth in life, including all the highest achievements of human culture, not least of all philosophy.[58][59]
According to St. Augustine and Thomas Aquinas, man's last end is happiness: "all men agree in desiring the last end, which is happiness."[60] However, where utilitarians focused on reasoning about consequences as the primary tool for reaching happiness, Aquinas agreed with Aristotle that happiness cannot be reached solely through reasoning about consequences of acts, but also requires a pursuit of good causes for acts, such as habits according to virtue.[61] In turn, which habits and acts that normally lead to happiness is according to Aquinas caused by laws: natural law and divine law. These laws, in turn, were according to Aquinas caused by a first cause, or God.[citation needed]
According to Aquinas, happiness consists in an "operation of the speculative intellect": "Consequently happiness consists principally in such an operation, viz. in the contemplation of Divine things." And, "the last end cannot consist in the active life, which pertains to the practical intellect." So: "Therefore the last and perfect happiness, which we await in the life to come, consists entirely in contemplation. But imperfect happiness, such as can be had here, consists first and principally in contemplation, but secondarily, in an operation of the practical intellect directing human actions and passions."[62]
Common market health measures such as GDP and GNP have been used as a measure of successful policy. On average richer nations tend to be happier than poorer nations, but this effect seems to diminish with wealth.[63][64] This has been explained by the fact that the dependency is not linear but logarithmic, i.e., the same percentual increase in the GNP produces the same increase in happiness for wealthy countries as for poor countries.[65][66][67][68] Increasingly, academic economists and international economic organisations are arguing for and developing multi-dimensional dashboards which combine subjective and objective indicators to provide a more direct and explicit assessment of human wellbeing. Work by Paul Anand and colleagues helps to highlight the fact that there many different contributors to adult wellbeing, that happiness judgement reflect, in part, the presence of salient constraints, and that fairness, autonomy, community and engagement are key aspects of happiness and wellbeing throughout the life course.
Libertarian think tank Cato Institute claims that economic freedom correlates strongly with happiness[69] preferably within the context of a western mixed economy, with free press and a democracy. According to certain standards, East European countries (ruled by Communist parties) were less happy than Western ones, even less happy than other equally poor countries.[70]
However, much empirical research in the field of happiness economics, such as that by Benjamin Radcliff, professor of Political Science at the University of Notre Dame, supports the contention that (at least in democratic countries) life satisfaction is strongly and positively related to the social democratic model of a generous social safety net, pro-worker labor market regulations, and strong labor unions.[71] Similarly, there is evidence that public policies that reduce poverty and support a strong middle class, such as a higher minimum wage, strongly affects average levels of well-being.[72]
It has been argued that happiness measures could be used not as a replacement for more traditional measures, but as a supplement.[73] According to professor Edward Glaeser, people constantly make choices that decrease their happiness, because they have also more important aims. Therefore, the government should not decrease the alternatives available for the citizen by patronizing them but let the citizen keep a maximal freedom of choice.[74]
It has been argued that happiness at work is one of the driving forces behind positive outcomes at work, rather than just being a resultant product.[75]
Several scales have been used to measure happiness:
The UK began to measure national well being in 2012,[83] following Bhutan which already measured gross national happiness.[citation needed]
A positive relationship has been found between the volume of gray matter in the right precuneus area of the brain and the subject's subjective happiness score.[84] Interestingly meditation, including mindfulness, based interventions have been found to correlate with a significant gray matter increase within the precuneus.[85][86][87][88][89]
In 2005 a study conducted by Andrew Steptow and Michael Marmot at University College London, found that happiness is related to biological markers that play an important role in health.[90] The researchers aimed to analyze whether there was any association between well-being and three biological markers: heart rate, cortisol levels, and plasma fibrinogen levels. Interestingly, the participants who rated themselves the least happy had cortisol levels that were 48% higher than those who rated themselves as the most happy. The least happy subjects also had a large plasma fibrinogen response to two stress-inducing tasks: the Stroop test, and tracing a star seen in a mirror image. Repeating their studies three years later Steptow and Marmot found that participants who scored high in positive emotion continued to have lower levels of cortisol and fibrinogen, as well as a lower heart rate.[citation needed]
In Happy People Live Longer (2011),[91] Bruno Frey reported that happy people live 14% longer, increasing longevity 7.5 to 10 years and Richard Davidson's bestseller (2012) The Emotional Life of Your Brain argues that positive emotion and happiness benefit long-term health.[citation needed]
However, in 2015 a study building on earlier research found that happiness has no effect on mortality.[92] "This "basic belief that if you're happier you're going to live longer. That's just not true."[93] Consistent results are that "apart from good health, happy people were more likely to be older, not smoke, have fewer educational qualifications, do strenuous exercise, live with a partner, do religious or group activities and sleep for eight hours a night."[93]
Happiness does however seem to have a protective impact on immunity. The tendency to experience positive emotions was associated with greater resistance to colds and flu in interventional studies irrespective of other factors such as smoking, drinking, exercise, and sleep.[94][95]
Despite a large body of positive psychological research into the relationship between happiness and productivity,[96][97][98] happiness at work has traditionally been seen as a potential by-product of positive outcomes at work, rather than a pathway to success in business. However a growing number of scholars, including Boehm and Lyubomirsky, argue that it should be viewed as one of the major sources of positive outcomes in the workplace.[75][99]
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Happiness - Wikipedia, the free encyclopedia
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Stem Cell 100 – Powerful Rejuvenation and Anti-Aging …
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Stem Cell 100 is formulated to rejuvenate your body and slow the aging process to help you feel and function more like a young person. This can help you feel better, look younger and improve your health. Most of the cells in your body lose function with age. Everyone has special cells called adult stem cells which are needed to rejuvenate damaged and old tissues, but adult stem cells themselves are also aging. Until now there was not much you could do about it. Stem Cell 100 rejuvenates adult stem cells and their micro-environments. Stem Cell 100+ is a more advanced and faster acting version of Stem Cell 100.
Developed by experts in the anti-aging field, patent-pending Stem Cell 100 is the only supplement proven to double maximum lifespan of an animal model. No other product or therapy including caloric restriction even comes close.
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Harness the Power of Your Own Stem Cells
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Stem Cell 100 Helps to Support:
The statements above have not been reviewed by the FDA. Stem Cell 100 is not a preventive or treatment for any disease.
Help Rejuvenate Your Body by Boosting Your Own Stem Cells
As a child, we are protected from the ravages of aging and can rapidly recover from injury or illness because of the ability of the young regenerative stem cells of children have a superior ability to repair and regenerate most damaged tissues. As we age, our stem cell populations become depleted and/or slowly lose their capacity to repair. Moreover, the micro-environment (i.e. niches) around stem cells becomes less nurturing with age, so cell turnover and repair are further reduced. This natural progression occurs so slowly that we are barely aware of it, but we start to notice the body changes in our 20s, 30s, 40s, and especially after 50 years of age. Stem Cell 100 helps adults regain their youthful regenerative potential by stabilizing stem cell function.
Stem Cell 100 works differently than other stem cell products on the market
You may have seen a number of products that are advertised as stimulating or enhancing the number of stem cells. Each person only has a limited number of stem cells so using them up faster may not be a good strategy. Stem Cell 100 is about improving the effectiveness and longevity of your stem cells as well as preserving the stem cell micro-environment. That should be the goal of any effective stem cell therapy and is what Stem Cell 100 is designed to do and what other stem cell products cannot do.
Stem Cell 100 Extends Drosophila (Fruit Fly) Lifespan
In extensive laboratory testing Stem Cell 100 greatly extended both the average and maximum lifespan of Drosophila fruit flies. The study (see Charts below) included three cages of Drosophila fruit flies that were treated with Stem Cell 100 (Cages T1 to T3) and three cages which were untreated controls (Cages C1 to C3). Each cage started with 500 fruit flies including 250 males and 250 females. The experiment showed that median lifespan more than doubled with a 123% increase. While fruit flies are not people they are more like us than you might think. Drosophila have a heart and circulatory system, and the most common cause of death is heart failure. Like humans and other mammals (e.g. mice), it is difficult to increase their lifespan significantly. These observed results outperform every lifespan enhancing treatment ever tested - including experiments using genetic modification and dietary restriction.
The longest living fruit fly receiving Stem Cell 100 lived 89 days compared to the longest living untreated control which lived 48 days. It is possible that the single longest living fruit fly lived longer for other reasons such as genetic mutation, however, there were many others that lived almost as long so it was not just an aberation. The oldest 5% of the treated fruit flies lived 77% longer than the oldest 5% of the control group. It is also important that the study showed an improved ability of the fruit flies to survive stress and illness at all ages not just during old age. Even after the first few days of the study there were already more of the Stem Cell 100 treated fruit flies alive that survived youth than the control group of untreated fruit flies. For additional information about the study please go to our Longevity page.
Supplement Facts
Stem Cell 100 is a Patent-Pending Life Code Nutraceutical. All Life Code products are nutraceutical grade and provide the best of science along with the balance of nature.
All Life Code products are nutraceutical grade and provide the best of science along with the balance of nature.
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Stem Cell 100 Plus+ is a more powerful and faster acting version of Stem Cell 100.
Click label to enlarge
Serving Size: One type O capsule
Servings Per Container: 60 Capsules
Recommended Use: Typical usage of Stem Cell 100 is two capsules per day, preferably at meal times. While both capsules can be taken at the same time, it is preferable to separate the two capsules by at least 4 hours. Since Stem Cell 100 is a potent formulation, do not take more than three capsules per day. One capsule per day may be sufficient for those below 110 pounds.
Recommended Users: Anyone from ages 22 and up could benefit from Stem Cell 100. Those in their 20s and 30s will like the boost in endurance during sports or exercise, while older users will notice better energy and general health with the potential for some weight loss.
Active Ingredients in Stem Cell 100: There are ten herbal components that make up the patent-pending combination in Stem Cell 100. The herbal components are highly extracted natural herbs that are standardized for active components that promote adult stem cells and lower inflammation:
1) Polysaccharides, flavonoids, and astragalosides extracted from Astragalus membranaceus, which has many positive effects on stem cells and the cardiovascular and immune systems.
2) Proprietary natural bilberry flavonoids and other compounds from a stabilized nutraceutical grade medicinal Vaccinium extract. Activate metabolic PPARS and helps produce healthy levels of cholesterol and silent inflammation. Also has anti-fungal and anti-viral activity.
3) Flavonoids and oligo-proanthocyanidins (OPCs) extracted from Pine Bark, which greatly reduce oxidative stress, DNA damage, and inflammation.
4) L-Theanine, which is a natural amino acid from Camellia sinesis that reduces mental stress and inflammation while improving cognition and protecting brain cells from ischemic or toxic injury.
5) Pterocarpus Marsupium, which contains two stable resveratrol analogs which promote stem cells, lower inflammation, and stabilized metabolism.
6) Polygonum Multiflorium stem stem is a popular Chinese herbal tonic that fights premature aging and promotes youthfulness. Polygonum is reported to enhance fertility by improving sperm count in men and egg vitality in women. Polygonum is also widely used in Asia to strengthen muscle and is thus used by many athletes as an essential tonic for providing strength and stamina to the body. Modern research has supported Polygonum multiflorium stem in that animal studies have proven that it can extend lifespan and improve the quality of life. Polygonum appears to protect the liver and brain against damage, perhaps by improving immune and cardiovascular health. The stem sections of Polygonum multiflorium are also calming to the nervous system and promote sounder sleep. Life Code uses a proprietary Polygonum multiflorium stem extract.
7) Schisandra Berry is used by many Chinese women to preserve their youthful beauty. For thousands of years, Schisandra has been prized as an antiaging tonic that increases stamina and mental clarity, while fighting stress and fatigue. In Chinese traditional medicine, Schisandra berry has been used for liver disorders and to enhance resistance to infection and promote skin health and better sleep. Schisandra berry is classified as an adaptogen, which can stimulate the central nervous system, increase brain efficiency, improve reflexes, and enhance endurance. Modern research indicates that Schisandra berry extracts have a protective effect on the liver and promote immunity. A double-blind human trial suggested that Schisandra berry may help patients with viral hepatitis, which is very prevalent in China. Recent work indicates that the liver is protected by the enhanced production of glutathione peroxidase, which helps detoxify the liver. Life Code uses a proprietary Schisandra berry extract.
8) Fo-Ti Root (aka He-Shou-Wu) is one of the most widely used Chinese herbal medicines to restore blood, kidney, liver, and cardiovascular health. Fo-Ti is claimed to have powerful rejuvenating effects on the brain, endocrine glands, the immune system, and sexual vigor. Legend has it that Professor Li Chung Yun took daily doses of Fo-Ti to live to be 256 and is said to have outlived 23 wives and spawned 11 generations of descendents before his death in 1933. While it is unlikely that he really lived to such an old age there is scientific support for Fo-Ti as beneficial for health and longevity. Like the Indian Keno bark, Fo-ti contains resveratrol analogs and likely acts by various mechanism, which includes liver detoxification and protection of skin from UVB radiation. Life CodeTM uses a proprietary Fo-Ti root extract.
9 ) Camellia sinensis has many bioactive polyphenols including the potent epigallocatechin-3-gallate (EGCG). A 2006 Japanese study published in the Journal of the American Medical Association reports that adults aged 40 to 79 years of age who drank an average of 5 or more cups of tea per day had a significantly lower risk of dying from all causes (23% lower for females and 12% lower for males). The study tracked more than 40,000 adults for up to 11 years and found dramatically lower rates of cardiovascular disease and strokes in those drinking 5 or more cups of tea. Many studies have found that adults drinking 3 or more cups of tea per day have significantly less cancer. Other studies have found that green tea helps protect against age-related cognitive decline, kidney disease, periodontal disease, and type 2 diabetes. Green tea also promotes visceral fat loss and higher endurance levels. Summarizing all of the thousands of studies on tea and tea polyphenols that have been published, it can be concluded that tea polyphenols preserve health and youth. This conclusion is backed up by gene studies showing that tea polyphenols decrease insulin-like growth factor-1 (IGF-1), which is a highly conserved genetic pathway that has been strongly linked to aging in yeast, worms, mice, and humans. If everyone could drink 4 to 5 cups of green tea each day, they could enjoy these important health benefits, but for most people drinking that much green tea can disturb their sleep patterns. Life Code uses a nutraceutical grade green tea extract that has 98% polyphenols and 50% ESCG that provides the polyphenol and ESCG equivalent of 4 to 5 cups of green tea with only 2% of the caffeine. Thus, most or all of the benefits of green tea are provided without concerns about disturbing sleep.
10) Drynaria Rhizome is used extensively in traditional Chinese medicine as an effective herb for healing bones, ligaments, tendons, and lower back problems. Eastern martial art practitioners have used Drynaria for thousands of years to help in recovering from sprains, bruises, and stress fractures. Drynaria has also helped in many cases of bleeding gums and tinnitus (ringing in the ears). The active components of Drynaria protect bone forming cells by enhancing calcium absorption and other mechanisms. Drynaria is also reported to act as a kidney tonic and to promote hair growth and wound healing. Life Code uses a proprietary Drynaria rhizome extract.
Active Ingredients in Stem Cell 100+ There are 11 herbal extracts in Stem Cell 100+ along with two nutraceutical grade vitamins Methyl Folate (5-MTHF) and Methyl B12 that are bioavailable vitamin supplements that are highly potent but rarely found. The highly extracted natural herbs are standardized for active components that promote adult stem cells and lower inflammation and have been tested as a synergistic herbal formulation with the proper dosage of each component:
1) Polysaccharides, flavonoids, and astragalosides extracted from Astragalus membranaceus, which has many positive effects on stem cells and the cardiovascular and immune systems. Astragalus has been used for thousands of years in Traditional Chinese Medicine (TCM) to promote cardiovascular and immune health. Astragalus is also known as a primary stimulator of Qi (Life Force). Life Code uses a high quality proprietary TCM extract that tested highest in our longevity experiments.
2) Proprietary natural bilberry flavonoids and other compounds from a stabilized nutraceutical grade medicinal Vaccinium extract. Activate metabolic PPARS and helps produce healthy levels of cholesterol and silent inflammation. Also has anti-fungal and anti-viral activity.
3) Flavonoids and oligo-proanthocyanidins (OPCs) extracted from Pine Bark, which promote the vascular system and reduce oxidative stress, DNA damage, and inflammation.
4) L-Theanine, which is a natural amino acid from Camellia sinesis that reduces mental stress and inflammation while improving cognition and protecting brain cells from ischemic or toxic injury. Life Code tested supplement with Mass Spec to verify high purity.
5) Genistein, which is an isoflavone phytoestrogen, activates telomerase, metabolic PPARs, autophagy (cell waste disposal), and smooth muscles. It also inhibits DNA methylation and the carbohydrate transporter GLUT1. Life Code tested supplement with Mass Spec to verify high purity.
6) Harataki Extract (aka Terminalia chebula) contains rejuvenating tannin flavonoids that have doubled human cell longevity in culture while maintaining telomere length. In Traditional Indian Medicine, Harataki has been used to treat skin disorders and heart disease, among many other uses.
7) Two stable resveratrol analogs from extracts of Pterocarpus Marsupium, which promote stem cells, less silent inflammation, and better metabolism. Life Code uses a highly purified proprietary source that is only available to Indian doctors. Life Code does not recommend taking resveratrol supplements or synthetic analogs, as these supplements are inherently unstable.
8) He-Shou-Wu is one of the most widely used Chinese herbal medicines to restore blood, kidney, liver, and cardiovascular health. He-Shou-Wu is claimed to have powerful rejuvenating effects on the brain, endocrine glands, the immune system, and sexual vigor. Legend has it that Professor Li Chung Yun took daily doses to live to 256 years and is said to have outlived 23 wives and spawned 11 generations of descendants before his death in 1933. While it is unlikely that he really lived to such an old age, there is scientific support for He-Shou-Wu as beneficial for health and longevity. Life Code uses a proprietary TCM He-Shou-Wu root extract.
9) Schisandra Berry is used by many Chinese women to preserve their youthful beauty. For thousands of years, Schisandra has been prized as an antiaging tonic that increases stamina and mental clarity, while fighting stress and fatigue. In TCM, Schisandra berry has been used for liver disorders and to enhance resistance to infection and promote skin health and better sleep. Schisandra berry is classified as an adaptogen, which can stimulate the central nervous system, increase brain efficiency, improve reflexes, and enhance endurance. Life Code uses a proprietary TCM extract.
10) Drynaria Rhizome is used extensively in TCM as an effective herb for healing bones, ligaments, tendons, and lower back problems. Eastern martial art practitioners have used Drynaria for thousands of years to help in recovering from sprains, bruises, and stress fractures. The active components of Drynaria protect bone forming cells by enhancing calcium absorption and other mechanisms. Drynaria is also reported to act as a kidney tonic and to promote hair growth and wound healing. Life Code uses a proprietary TCM Drynaria rhizome extract.
11) BioPerine is a proprietary brand of peperine extracted from black pepper. BioPerine has been shown to enhance bioavailability of herbal extracts. Piperine has been shown in rats to have cognitive enhancing effects and to help control silent inflammation.
Safety: The extracts in Stem Cell 100 and Stem Cell 100+ are nutraceutical grade and have been individually tested in both animals and humans without significant safety issues. Those with pre-existing conditions of diabetes or hypertension should coordinate this product with your doctor, as lower blood glucose or reduced blood pressure can result from taking the recommended dose of this product.
Warnings: may lower glucose and/or blood pressure in some individuals. The supplement is not recommended for pregnant, lactating, or hypoglycemic individuals.
References
1. Yu, Q., Y.S. Bai, and J. Lin, [Effect of astragalus injection combined with mesenchymal stem cells transplantation for repairing the Spinal cord injury in rats]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2010. 30(4): p. 393-7.
2. Xu, C.J., et al., [Effect of astragalus polysaccharides on the proliferation and ultrastructure of dog bone marrow stem cells induced into osteoblasts in vitro]. Hua Xi Kou Qiang Yi Xue Za Zhi, 2007. 25(5): p. 432-6.
3. Xu, C.J., et al., [Effects of astragalus polysaccharides-chitosan/polylactic acid scaffolds and bone marrow stem cells on repairing supra-alveolar periodontal defects in dogs]. Zhong Nan Da Xue Xue Bao Yi Xue Ban, 2006. 31(4): p. 512-7.
4. Zhu, X. and B. Zhu, [Effect of Astragalus membranaceus injection on megakaryocyte hematopoiesis in anemic mice]. Hua Xi Yi Ke Da Xue Xue Bao, 2001. 32(4): p. 590-2.
5. Qiu, L.H., X.J. Xie, and B.Q. Zhang, Astragaloside IV improves homocysteine-induced acute phase endothelial dysfunction via antioxidation. Biol Pharm Bull, 2010. 33(4): p. 641-6.
6. Araghi-Niknam, M., et al., Pine bark extract reduces platelet aggregation. Integr Med, 2000. 2(2): p. 73-77.
7. Rohdewald, P., A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology. Int J Clin Pharmacol Ther, 2002. 40(4): p. 158-68.
8. Koch, R., Comparative study of Venostasin and Pycnogenol in chronic venous insufficiency. Phytother Res, 2002. 16 Suppl 1: p. S1-5.
9. Rimando, A.M., et al., Pterostilbene, a new agonist for the peroxisome proliferator-activated receptor alpha-isoform, lowers plasma lipoproteins and cholesterol in hypercholesterolemic hamsters. J Agric Food Chem, 2005. 53(9): p. 3403-7.
10. Manickam, M., et al., Antihyperglycemic activity of phenolics from Pterocarpus marsupium. J Nat Prod, 1997. 60(6): p. 609-10.
11. Grover, J.K., V. Vats, and S.S. Yadav, Pterocarpus marsupium extract (Vijayasar) prevented the alteration in metabolic patterns induced in the normal rat by feeding an adequate diet containing fructose as sole carbohydrate. Diabetes Obes Metab, 2005. 7(4): p. 414-20.
12. Mao, X.Q., et al., Astragalus polysaccharide reduces hepatic endoplasmic reticulum stress and restores glucose homeostasis in a diabetic KKAy mouse model. Acta Pharmacol Sin, 2007. 28(12): p. 1947-56.
13. Schafer, A. and P. Hogger, Oligomeric procyanidins of French maritime pine bark extract (Pycnogenol) effectively inhibit alpha-glucosidase. Diabetes Res Clin Pract, 2007. 77(1): p. 41-6.
14. Kwak, C.J., et al., Antihypertensive effect of French maritime pine bark extract (Flavangenol): possible involvement of endothelial nitric oxide-dependent vasorelaxation. J Hypertens, 2009. 27(1): p. 92-101.
15. Xue, B., et al., Effect of total flavonoid fraction of Astragalus complanatus R.Brown on angiotensin II-induced portal-vein contraction in hypertensive rats. Phytomedicine, 2008.
16. Mizuno, C.S., et al., Design, synthesis, biological evaluation and docking studies of pterostilbene analogs inside PPARalpha. Bioorg Med Chem, 2008. 16(7): p. 3800-8.
17. Sato, M., et al., Dietary pine bark extract reduces atherosclerotic lesion development in male ApoE-deficient mice by lowering the serum cholesterol level. Biosci Biotechnol Biochem, 2009. 73(6): p. 1314-7.
18. Kimura, Y. and M. Sumiyoshi, French Maritime Pine Bark (Pinus maritima Lam.) Extract (Flavangenol) Prevents Chronic UVB Radiation-induced Skin Damage and Carcinogenesis in Melanin-possessing Hairless Mice. Photochem Photobiol, 2010.
19. Pavlou, P., et al., In-vivo data on the influence of tobacco smoke and UV light on murine skin. Toxicol Ind Health, 2009. 25(4-5): p. 231-9.
20. Ni, Z., Y. Mu, and O. Gulati, Treatment of melasma with Pycnogenol. Phytother Res, 2002. 16(6): p. 567-71.
21. Bito, T., et al., Pine bark extract pycnogenol downregulates IFN-gamma-induced adhesion of T cells to human keratinocytes by inhibiting inducible ICAM-1 expression. Free Radic Biol Med, 2000. 28(2): p. 219-27.
22. Rihn, B., et al., From ancient remedies to modern therapeutics: pine bark uses in skin disorders revisited. Phytother Res, 2001. 15(1): p. 76-8.
23. Saliou, C., et al., Solar ultraviolet-induced erythema in human skin and nuclear factor-kappa-B-dependent gene expression in keratinocytes are modulated by a French maritime pine bark extract. Free Radic Biol Med, 2001. 30(2): p. 154-60.
24. Van Wijk, E.P., R. Van Wijk, and S. Bosman, Using ultra-weak photon emission to determine the effect of oligomeric proanthocyanidins on oxidative stress of human skin. J Photochem Photobiol B, 2010. 98(3): p. 199-206.
25. Haskell, C.F., et al., The effects of L-theanine, caffeine and their combination on cognition and mood. Biol Psychol, 2008. 77(2): p. 113-22.
26. Owen, G.N., et al., The combined effects of L-theanine and caffeine on cognitive performance and mood. Nutr Neurosci, 2008. 11(4): p. 193-8.
27. Yamada, T., et al., Effects of theanine, a unique amino acid in tea leaves, on memory in a rat behavioral test. Biosci Biotechnol Biochem, 2008. 72(5): p. 1356-9.
28. Jia, R.Z., et al., [Neuroprotective effects of Astragulus membranaceus on hypoxia-ischemia brain damage in neonatal rat hippocampus]. Zhongguo Zhong Yao Za Zhi, 2003. 28(12): p. 1174-7.
29. Nathan, P.J., et al., The neuropharmacology of L-theanine(N-ethyl-L-glutamine): a possible neuroprotective and cognitive enhancing agent. J Herb Pharmacother, 2006. 6(2): p. 21-30.
30. Nobre, A.C., A. Rao, and G.N. Owen, L-theanine, a natural constituent in tea, and its effect on mental state. Asia Pac J Clin Nutr, 2008. 17 Suppl 1: p. 167-8.
31. Murakami, S., et al., Effects of oral supplementation with cystine and theanine on the immune function of athletes in endurance exercise: randomized, double-blind, placebo-controlled trial. Biosci Biotechnol Biochem, 2009. 73(4): p. 817-21.
32. Kawada, S., et al., Cystine and theanine supplementation restores high-intensity resistance exercise-induced attenuation of natural killer cell activity in well-trained men. J Strength Cond Res, 2010. 24(3): p. 846-51.
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Stem Cell 100 - Powerful Rejuvenation and Anti-Aging ...
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Colonization Home Page
Posted: September 6, 2016 at 8:08 am
The Continental Congress - Founding Fathers:
Lost New York runs using HTML TADS Interpreter 3 LOSTNY.zip (353Kbytes) WinZip File, by Neil deMause. "As a bored tourist in the Big Apple, you discover a time-travel device that lets you witness first-hand the development of the city in four centuries. A well-researched period piece with good wry descriptive prose, rather sad in many places about the passing of old landmarks and the ruthlessness of modernity. Good explorability, although towards the end trekking about and waiting for trains can get to be a chore. The puzzles are mostly (but not entirely) straightforward, but careful examination of scenery is required to obtain equipment. The geography is representative rather than exhaustive - walking north from 14th Street, for example, takes you to 23rd Street."
New York City, New York State - one of the Great Cities of the World. Site of Interest: (1) The Battery Park, (2) The Brooklyn Bridge, (3) Central Park, (4) Empire State Building and Grand Central Station, (5) Wall Street, (6) Pennsylvania Station, going to Carolina, Pennsylvania, Vermont, Long Island, and New Jersey.
Other attractions include the Statue of Liberty [built 1886] (on Liberty Island), Ellis Island [1892-1954] (were European Immigrants came in), the United Nations Building (in the Upper East Side, next to Queens Borough Bridge), and lots of Museums. And New Style Taxis, Hotels, Bloomingdale's Department Store, Staten Island Ferry, and JFK Airport on Long Island. 'the El' or Subway Train Network has several branches including the Hudson Line, Harlem Line, New Haven Line, New Canaan Branch, and Danbury Branch.
As an aside, it is known Randolph and Mortimer from the Trading Place's Movie live by the Hudson River, in the West Bronx Borough. New York City is also home to Marvel Comics: Superman, Spiderman, Johnny Voltaire etc...
The name Ledgard is of Norman French origin, Anglicized during one of our numerous Wars with France ending with the Napoleonic Wars. It means 'Keeper of the Keep' - their Job was to raise and lower the Drawbridge and Portcullis which protected the entrance to the Castle. A Portcullis is on the 1 Pence Coin.
William I (the Conquer - as Duke of Normandy) was the First King in the British Royal Family. In 1066 at the Battle of Hastings (in East Sussex) he beat the Anglo-Saxon King Harold II. Who had just repelled the Viking King Harold Harade at the Battle of Stamford Bridge, Fulford near York; and force marched his men to Southern England.
King William was Crowned King of England at Westminster Abbey on Christmas Day 1066. And the Normans soon built a network of Motte and Bailey Wooden Castles up and down the Country. Founding Newport SE Wales, and Newcastle as frontier Towns. The Tower of London in East London on the Thames was built as a Royal Castle for the King and his entourage. Later Castles were rebuilt in Stone, as were new Cathedrals and Monasteries.
I had a friend called Sleigh (a Norman Foot Soldier) who worked as a High Level Computer Programmer for battery monitoring equipment which a two PIC Microcontrollers on each battery. One read the battery Ampage, the other Rx and Tx signals down a fibre optic loop to a Psion Computer that reported if the battery was faulty. He likes going the caf and is from East London, and a bit of a Geezer. He says there aren't any houses for local people to move in to to start a family in London.
My Brother Jonathan looks a lot like the TV personality Frasier, and seems to have 1/3 Norman Blood which makes his strong and confident, while being decent and compassionate, re-emerging from a Ancestor way back when buried in the DNA.
My Genome, by David Magnus Ledgard:
Peoples who have excelled in the Fields of Invention, Culture, and Manufacturing:
Southern Italy is Poor because it is too hot to work much, except on the land. They grow the Olive in Southern Italy, and Greece, for Olive Oil to cook with, or make healthy 'Butter' Margarine. Italy also makes Beef, Milk (for Cheese), Tomatoes (without Greenhouse) and Wheat (for Spaghetti), and Garlic. Also Italy is fond of Coffee e.g. Cappuccino, Mocha (half Chocolate), or Latte. There used to be a lot of Lemons grown in Sicily once, but it's Population is greater now.
There are also two other important jobs:
What are WizKids??? WizKids are young people who know about Computers, programme them, enjoy programming them, and make something Fun or Useful. Like Bill Gates of Microsoft Fame who programmed MS-DOS (Microsoft Disk Operating System [5.25 Inch Disk]), and Windows 95 / 98. With some help. When Men were Men, and Programmers were Programmers listings used to come with ribbon feed, and you could look right done the listing as each page was connected to the other.
You may have noticed there have been a lot of Intel Microprocessor types coming out lately. Here is a list of some of the IBM Clone PC (Personnel Computer) Chipsets by Intel:
Currently there are 10 Million Computers with a Base Unit, Keyboard, Mouse, and Monitor of type Pentium IV, and Core Multi-processors in Warehouses in the East, and the United States of America. As Computers use a lot of Rare Metals it seems a waste that they aren't used, or sold at a knock down price. There have been endless Laptops made which have very little Software on them. Just film websites, and office programmes. There seems to be a desperate shortage of Software, and 2D and Strategy Computer Games. FEW NEW COMPUTERS are being sold because people might forget their passwords stored in "cookies", and they have to copy all files across - either by going to the Computer Shop, or using the Read/Write CD-ROM (Compact Disk ROM). Remember you can order a Proper Computer with Big Screen and Keyboard from DELL off the internet with a Base Unit. Don't Forget to Buy a Manual from amazon.co.uk for example in e.g. BASIC Programming.
The well known and liked Micro-Computers the Commodore 64, and BBC Micro where 8-bit (1-byte) Computers. This meant they could have Colour 0-255. 16-bit (2-byte, or Word) Computers like the very popular Commodore Amiga could have richer Colour 0-65536. 32-bit (4-byte, or Longword) Windows PC Computers could have xxRRGGBB ($00-$FF) Red-Green-Blue Colour. Which can make Red (xxFF0000) for example or any mix of Colours. The Nintendo 64 has 64-bit (8-byte, or Octbyte) i.e.. 4 x 16 lines on it's custom built chip. No 128-bit Computer ever seems to have been made as it is 'inconceivable and 'near infinitely complex'.
Networks of Transputer Computer Chips can be connected together to make a super-computer with Parallel Processing. Used to make Computer Graphics and Films like 'toystory'.
The Microprocessor I learned consisted of a ALU (Arithmetic and Logic Unit), RAM (Read Only Memory), and Control Unit (which processed Op-codes, the Accumulator, and the Status Register). The BASIC programme itself could be stored in ROM (Read Only Memory), now most of it is on the Hard Disk Drive. The 3.5" floppy disk has fallen out of use, as did the 5.25" drive before it.
Example Op-codes (also known as Mnemonics by some people - written perfectly by some very clever and thoughtful Computer Scientists) include:
Variables are required to Run a Computer Programme:
There is also a Status Register with Flags like Division by Zero Error (if this happens the computer crashes); Carry (if two 8-bit numbers are added they might go one to make a 9-bit number - this is stored in the Carry Bit); Branch (Equal, or NOT Equal - for the IF/THEN/ELSE Statement).
A letter can be stored as an 8-bit Number (0-255) in ASCII (American Standard Code for Information Interchange): 0-31 are control codes like 7 for the BELL sound, or 13 for Carriage Return; 32 is Space; 48-57 is 0-9; 65-89 is A-Z; 97-116 is a-z (+32, or twiddle bit 6 to TRUE). C is good at bit twiddling.
As an interesting point of Mathematics and Physics it is said that 1/0 (one divided by 0) has no meaning or is infinite!!!!!
ROM's (Read Only Memory):
The BASIC Programming Language [Beginners All-purpose Symbolic Instruction Language] was designed by Dartmouth Naval College New England.
What Happened to the Old COMPUTER MANUAL? It used to tell you how to do all types of things on a Computer. The Electronic One is hardly ever Read. It was the Computer Programmers BIBLE. For BASIC, Pascal, Windows 95...
There are two famous BASIC programmes for Beginners, or Quick BASIC if you use labels and not line numbers, it compiles as it runs i.e. a run-time language:
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What’s your favorite politically incorrect joke? : AskReddit
Posted: at 8:07 am
2550 points
What is your go to Tinder Alternative?
5137 points
Redditors who go into peoples' houses for their job, what is the strangest/creepiest thing you've ever seen or experienced?
440 points
You're in a car full of diverse strangers and they hand you the aux. What song do you play in order to please as many of them as possible?
880 points
Which 2 entire countries should have sex with one another and create a baby country?
4580 points
Pick any 2 movies from the same actor. Those movies are now part of the same reality. What happened to the actor to get them from movie A to movie B?
584 points
Waiters, waitresses, and bartenders of Reddit: You guys are involved in some big moments in some people's lives (engagements, anniversaries, birthdays, etc.). How did you fuck it up for them?
845 points
What's the worst way you've been defeated by an inanimate object?
312 points
[Serious] People who have known a serial killer/murderer prior to the murders, how did you react? Did you see it coming?
764 points
Reddit, what's the truest version of "There are two kinds of people in this world..."?
2219 points
What are some subcultures most people are probably completely unaware of?
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U.S. Navy Held Meetings With Transhumanist to Discuss …
Posted: at 8:06 am
By Joseph Jankowski
The U.S. Navy has held meetings with American presidential hopeful and TranshumanistZoltan Istvan to discuss thepossibility of implanting humans with microchips fitted with global positioning (GPS) technology, reports The Sun.
AccordingtoVice Admiral Wisecup, who has retired from full-time service to work in a Navy department called the Chief of Naval Operations Strategic Studies Group, the meeting broadened our understanding of the merger of humans and machines.
A bunch of navy officers came to my house and one of the main topics was this chip implant strategy, Transhumanist and Futurist Istvan said.
Zoltan Istvan is currently running for president of the United States as a part of the Transhumanist Party.
The Transhumanist Party aims to uphold the energy and political might of millions of transhumanist advocates out there who desire to use science and technology to significantly improve their lives.
Istvan told The Sun that the Navy is worried that soldiers could enter service with chips already implanted into them and is struggling to create policy around this issue.
You can imagine how challenging that would be if someone had a non-authorized chip implant on a nuclear base, so policy has to be created and created soon, says Istvan.
I helped the US Navy do some policy work on this issue.
The presidential candidate believes that within 10 to 15 years, artificial intelligence will advance to the point of solving all of civilizations most vexing problems, including death, and he has even traveled around America in an immortality bus mocked up like a coffin to promote his ideas.
According to Istvan, themilitary has already experimented with chipping soldiers so they can be tracked.
Its crazy to me that we dont develop it and use it in ourselves (humans) more, and especially in our children, says the Transhumanist.
Istvan believes that GPS microchipping could be beneficial to parents who want to be able to keep track of their children and could have allowed investigators to find the body of Lane Graves, who was killed in an alligator attack, in just a matter of minutes.
As a father of a twoand five-year-old, Im a big believer in the future that all children will get chipped, perhaps like all children get vaccines in the US, Istvan told The Sun.
Joseph Jankowski is a contributor for Planet Free Will.com. His works have been published by recognizable alternative news sites like GlobalResearch.ca, ActivistPost.com, Mintpressnews.com andZeroHedge.com.
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Futurism and Preterism – Amazing Discoveries
Posted: at 8:06 am
The Reformation preachers unanimously identified the papal system as the Antichrist, and the Roman Church as Babyloncausing a mass exodus of believers out of the Catholic institution.
Because Rome realized that the Reformation could jeopardize her position as a religio-political power, she employed five strategies in what became known as the Counter Reformation. One of those strategies was the creation of futurism and preterism, two different interpretations of the prophecies in Daniel and Revelation. These interpretations contradicted the reformers' stance of historicism.
The Oxford Handbook of Eschatology says that futurism argues that Revelation looks beyond the first century to the period immediately before the end times. Thus the book was not written for those who received it, but for those living much later. Jesuit scholars after the Reformation refined this approach to prove that current attempts to identify the Pope as the Antichrist could not possibly be true since the Antichrist will not be revealed until far into the future, just before the Parousia (Christs Second Coming)."i
The same book explains that preterism sees Revelation only in terms of its immediate historical context: Revelation [is] described [as] the plight of Christians in the late first century, and its apocalyptic symbols pointed directly to [the city of] Rome as the churchs persecutor...Most modern [preterist] interpreters...insist that the book was never intended to predict conditions or events beyond the first century.ii
According to futurism, the Antichrist is still to come. According to preterism, the Antichrist was in the past. However, this is not Biblical, as Jesus spoke in Matthew 24 of the great apostasy taking place in the future. Both of these false systems disagree with the reformers belief that the fulfillment of Biblical prophecy is taking place throughout history.
Throughout the Counter Reformation, preterism and futurism diverted attention away from prophecies identifying the Roman Church as Babylon and the papal system as the Antichrist.
Here is a diagram to help us understand how these false interpretations were created and spread. In this diagram, you can see that the 1260 years of the Dark Ages was the period of papal supremacy prophesied in Daniel and Revelation.iii
Francisco Ribera In 1585 Jesuit scholar Francisco Ribera (1537 - 1591) appears. He started the futurist interpretation by publishing a 500-page commentary on the book of Revelation. Ribera took the last week (seven day-years) of the 70-week prophecy of Daniel 9:25, divided it into two 3 year periods, and applied it to a future Antichrist, while avoiding any application to the papal system.
Robert Bellarmine Riberas views would have fallen away quickly if not for Robert Bellarmine (1542 - 1621), a cardinal who promoted Riberas ideas. His lectures were published as Polemic Lectures Concerning the Disputed Points of the Christian Belief Against Heretics of This Time. Froom describes these lectures as the most detailed apology of the Catholic faith ever produced. Froom also says they became the arsenal for all future defenders and expositors.iv
Luis de Alcasar The diagram shows Jesuit scholar Luis de Alcasar (preterisms creator) in 1604. His book, Investigation of the Hidden Sense of the Apocalypse, was published in 1614. Froom states this:
Applying the New Jerusalem to the Catholic Church, Alcazar contended that the Apocalypse describes the twofold war of the church in the early centuriesone with the Jewish synagogue, and the other with paganismresulting in victory over both adversaries. Revelation 1 to 11 he applied to the rejection of the Jews and the desolation of Jerusalem by the Romans. Revelation 12 to 19 Alcazar allotted to the overthrow of Roman paganism and the conversion of the empire to the church, the judgment of the great Harlot being effected by the downfall of pagan idolatry; Revelation 20 he applied to the final persecution by Antichrist, and the day of judgment; and chapters 21 and 22, referring to the New Jerusalem, he made descriptive of the glorious and endless triumphant state of the Roman church.v
The Roman Church produced two contradictory interpretations of end-time prophecy, neither of which were true to Scripture.
In his book Truth Matters, Professor Walter Veith explains the following:
To counter the stand of the Reformers, the Catholic Church launched the counter-reformation spearheaded by the Jesuit Order. The doctrines of Preterism and Futurism, published by Alcasar and Ribera, two Jesuit priests, in 1585, redefined the reformation position on the Antichrist and shifted the emphasis away from the papacy to the Greek king Antiochus Epiphanus IV and to some tyrant who would persecute the Jews some time in the future.vi
Further, Professor Veith observes that by accepting these alternative approaches to Biblical prophecy, the Protestant world...saw in it an opportunity to cease hostilities with Rome.vii
Here the true danger is exposed: if Protestantism ceases to protest against the falsehoods of Rome, then there is no opposition to the Roman plans, and no check against the corruption of Biblical Christianity found in the Roman Catholic system. The Dark Ages can come again with a vengeance.
Want to learn more? Here is a list of informative resources from Walter Veith and Victor Gill:
Total Onslaught DVD series Rekindling the Reformation DVD series Professor Veiths bookTruth Matters These resources and many more are available from the Amazing Discoveries online store.
i. Jerry L. Walls, The Oxford handbook of eschatology (Oxford University Press, 2007).
ii. ibid.
iii. This diagram is adapted from a similar diagram on page 508 of Le Roy Edwin Froom, The Prophetic Faith of Our Fathers Volume 2 (Washington DC: Review and Herald, 1948).
iv. Le Roy Edwin Froom, The Prophetic Faith of Our Fathers Volume 2 (Washington DC: Review and Herald, 1948).
v. ibid.
vi. Walter Veith, Truth Matters (Amazing Discoveries, 2002).
vii. ibid.
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The Ron Paul Institute for Peace and Prosperity – About Us
Posted: September 3, 2016 at 11:31 pm
The Ron Paul Institute for Peace and Prosperity is a project of Dr. Pauls Foundation for Rational Economics and Education (F.R.E.E.), founded in the 1970s as an educational organization. The Institute continues and expands Dr. Pauls lifetime of public advocacy for a peaceful foreign policy and the protection of civil liberties at home.
The Institute mobilizes colleagues and collaborators of Dr. Pauls to participate in a broad coalition to educate and advocate for fundamental changes in our foreign and domestic policy.
A prosperous America is profoundly linked to a foreign policy rooted in peaceful relations and trade with all. With peace, comes real prosperity.
Ron Pauls real legacy in his writing, teaching, and in politics is his success bringing people of very different backgrounds and perspectives together under the common cause of peace, individual liberties, and prosperity. His institute energetically continues this kind of coalition-building in all aspects of its work. The Institute board is itself one of the best examples of how broad a coalition can come together and work for the same shared goals and values.
First and foremost a resource for supporters, the Institute provides timely news and provocative analysis through its engaging website. Features such as Congress Alert and Neo-Con Watch bring to life the latest threats to our liberties at home and abroad in a capsule format. Longer features and press analysis, as well as blog posts, regularly appear, giving the Institute the character of an online magazine.
The Institute places special emphasis on education and on the next generations, with a foreign policy summer school for university students studying international affairs and journalism.
It will aggressively promote student writing on foreign affairs on its website and will launch a student writing award program to recognize the best of college journalism.
The Ron Paul Institute will provide the tools and the education to chart a new course with the understanding that only through a peaceful foreign policy can we hope for a prosperous tomorrow. After a decade of US war against Iraq and Afghanistan, American public opinion is clearly turning against the wars. Barely half still support the war on Afghanistan and a clear majority now oppose the Iraq war.
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The Ron Paul Institute for Peace and Prosperity - About Us
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