Your lysosomes are recycling units, but their function slowly fails with age - meaning your cells degrade as they fill with waste and junk. More rapid and selective lysosomal failure in brain cells is implicated in a variety of neurodegenerative conditions. Here, researchers dig more deeply: "Neurodegenerative disorders, like Alzheimer's disease, are a devastating group of conditions that exact a heavy toll on patients and their families. ... Research over the past two decades has strongly suggested that a fundamental problem in affected nerve cells relates to accumulation of cellular 'garbage,' or proteins and other material that is too old to function properly. Thus, understanding how the neuron handles these outdated molecules is of great significance. Here we find that upregulation of one such cellular degrading pathway, the lysosome, can have significant deleterious effects to the neuron. We specifically show that expanding the lysosomal compartment can markedly increase production of a very toxic form of tau, a protein strongly implicated in neuronal dysfunction and death in Alzheimer's disease and related disorders. Our findings have important implications for the development of neurodegenerative disease therapies that seek to manipulate the lysosome and the proteins within the lysosome." Therapies that can repair failing lysosomes may have general application to rejuvenation medicine - so the more groups working on that, the better.

View the Article Under Discussion: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904797/

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

There is clearly a point in Alzheimer's, and other neurodegenerative diseases, beyond which the damage caused by the condition is irreversible. Neurons die, and in large enough numbers to destroy vast swathes of information held in the brain - the very foundation of who you are, and the vital components of systems needed to live a normal life. All is not gloom, however. Studies in past years have suggested that up to that point, much of the loss of function that accompanies Alzheimers is in principle reversible:

Some evidence suggests that the worst effects of Alzheimer's disease can be repaired - that memories are not destroyed, but rather become inaccessible.

Another recent study adds to this picture:

Amyloid-beta and tau protein deposits in the brain are characteristic features of Alzheimer disease. The effect on the hippocampus, the area of the brain that plays a central role in learning and memory, is particularly severe. However, it appears that the toxic effect of tau protein is largely eliminated when the corresponding tau gene is switched off.

Researchers from the Max Planck Research Unit for Structural Molecular Biology at DESY in Hamburg have succeeded in demonstrating that once the gene is deactivated, mice with a human tau gene, which previously presented symptoms of dementia, regain their ability to learn and remember, and that the synapses of the mice also reappear in part. The scientists are now testing active substances to prevent the formation of tau deposits in mice. This may help to reverse memory loss in the early stages of Alzheimer disease - in part, at least.

For yet another consideration of early to mid-stage Alzheimer's as a form of dynamic blockage of memory access, you might also look at the effects of some newer anti-inflammatory treatments:

The [study from 2008] documents a dramatic and unprecedented therapeutic effect in an Alzheimer's patient: improvement within minutes following delivery of perispinal etanercept, which is etanercept given by injection in the spine.

Putting aside a discussion of the mechanisms by which this happens, the very fact that it can happen demonstrates the possibility of reversing the worst aspects of Alzheimer's. Thus memories and the working structures of the brain must remain largely intact until fairly late in the progression of the disease.

Vitamin D has been linked to many health conditions before. A recent study links insufficient levels of the vitamin with the disabling condition depression

In a recent study performed by researchers from the National Institute of Aging in the United States, insufficient levels of vitamin D may be the reason why many individuals over the age of 65 are experiencing symptoms of depression.

Senior individuals often have low levels of the important vitamin because they tend to stay indoors more often, as opposed to younger, more sprightly individuals with more active lifestyles. The study was published in a medical journal on endocrinology this year.

According to Luigi Ferrucci, the lead researcher, the emerging link between vitamin D deficiency and the occurrence of depression must be further investigated.  The study involved a follow-up testing of nearly one thousand male and female respondents within a six-year period.

The researchers used a specialized scale that measured the symptoms of depression called CES-D.  The researchers discovered that those with lower levels of vitamin D in their blood tended to have poorer score in the CES-D test.  Those with higher vitamin D percentages in their blood scored better in the same test.

Alarming, global trend

Depression is fast becoming one of the leading causes of disability around the world, not just in the United States.  It is estimated that today, there are 120 million people afflicted with the condition.  Ferrucci’s study is not the first to point at the possible link between the vitamin and depression.

In an earlier study carried out two years ago, Dutch researchers reported that insufficient levels of the vitamin in the body resulted in a higher percentage of the parathyroid hormone.

This hormone, which is used by the body to regulate calcium loss, has been directly linked to a higher incidence of depression in some one thousand two hundred respondents in yet another independent study.  This is the reason why a causal pathway must be mapped out to determine just how this vitamin affects the human brain.

In a fourth related study, researchers McCann and Arnes noted that vitamin D is important for the proper functioning and health of the human brain.  The widespread presence of vitamin D receptors throughout the human brain is evidence of the vital role of the nutrient in brain health.

According to yet another scientific review, vitamin D has been associated with affecting proteins in the human brain that are responsible for governing the learning process and remembering.  If an imbalance occurs in these areas, you can just imagine a chain reaction occurring throughout the brain.

Benefits of vitamin D

There are several ways that you can get vitamin D: natural exposure to sunlight, food (like dairy products, e.g. yogurt, milk, etc.) and through vitamin supplementation.  The body only needs about 10 – 15 minutes of exposure to natural sunlight to produce vitamin D on its own.

If this is not possible, people with low levels of vitamin D should explore vitamin supplementation; this applies most especially to senior individuals who may not be eating well or are unable to engage in a more active lifestyle.  Instead of using sunscreen when going out to get your healthy dose of sunshine, you can protect your skin naturally by taking natural antioxidants like fresh wheatgrass juice and citrus fruits.

The usual recommended dose for adults is between 400 to 800 IU (international units) of vitamin D everyday. Pregnant women should be given a higher dose (800 IU) to ensure optimum bone health and proper development of the fetus.

And there are more reasons to love vitamin D! Here are some of the most important benefits:

1. It is needed for proper absorption and utilization of calcium and phosphorous.  It is needed for the proper maintenance and repair of the bones and skin.

2. It strengthens and helps maintain the immune function of the body. Conditions like flu and the common cold can be warded off more efficiently if the immune system is strengthened by vitamin D.

3. It is an important nutrient that prevents the occurrence of MS (multiple sclerosis).  According to researchers from the Oregon Health & Science University, MS is less frequent in tropical countries because there is more available sunshine in these places than in temperate regions.

4. Vitamin D has also been linked to the maintenance of normal body weight (according to research from the Medical College of Georgia).

5. Vitamin D is important for brain health in the later years (60 – 79 years of age).

6. In a recent study from the Harvard Medical School, vitamin D can also reduce asthma attacks in asthmatic individuals.

7. We are exposed continually to low levels of radiation.  The good news is vitamin D can also help protect us from such exposures.

According to US cancer researchers, people with adequate levels of vitamin D have a lower risk for many types of cancer than people with low or inadequate levels of the vitamin.

Sources:
nutraingredients.com
healthvitaminsguide.com
medicalnewstoday.com

Discuss this post in Frank Mangano’s forum!

Researchers are turning up new longevity genes at a fair rate these days, and this latest discovery is illustrative of the methods used - start with what you know, and compare and contrast: "A major challenge in translating the positive effects of dietary restriction (DR) for the improvement of human health is the development of therapeutic mimics. One approach to finding DR mimics is based upon identification of the proximal effectors of DR life span extension. Whole genome profiling of DR in Drosophila shows a large number of changes in gene expression, making it difficult to establish which changes are involved in life span determination as opposed to other unrelated physiological changes. We used comparative whole genome expression profiling to discover genes whose change in expression is shared between DR and two molecular genetic life span extending interventions related to DR, increased dSir2 and decreased Dmp53 activity. We find twenty-one genes shared among the three related life span extending interventions. One of these genes, takeout, thought to be involved in circadian rhythms, feeding behavior and juvenile hormone binding is also increased in four other life span extending conditions: Rpd3, Indy, chico and methuselah. We demonstrate takeout is involved in longevity determination by specifically increasing adult takeout expression and extending life span. These studies demonstrate the power of comparative whole genome transcriptional profiling for identifying specific downstream elements of the DR life span extending pathway."

View the Article Under Discussion: http://www.ncbi.nlm.nih.gov/pubmed/20519778

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

Accelerating Future notes an example of Alcor's work in cryonics provision. We only tend to hear about the times when unusual obstructions crop up, and so it's worth a reminder that Alcor's staff and volunteers regularly make the difficult organization of a cryosuspension look routine: "This past month, Alcor was faced with three members who were admitted to hospice with end-stage conditions. On back-to-back days, two of our members were cryopreserved while the third member's condition has temporarily improved. Through careful planning, we were able to have two members admitted into the same Hospice of the Valley facility, literally across the hall from each other. This allowed Alcor's Arizona team to carefully monitor both members' conditions simultaneously, 24 hours a day. Having three team members and Alcor's Rescue Vehicle on site, we were able to provide immediate stabilization and cool down procedures and exceptionally quick transfer from time of pronouncement to Alcor's surgery suite in 40 minutes and 32 minutes, respectively. These cases were very important as they tested numerous benchmarks of Alcor's abilities ... The real benefit of all of our preparations, training and planning is to our members, who reportedly received excellent perfusions."

View the Article Under Discussion: http://www.acceleratingfuture.com/michael/blog/2010/05/alcors-93rd-and-94th-patients-cryopreserved-back-to-back/

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

A number of past studies have shown improvement in Parkinson's disease with stem cell transplants. Here is another: "Endometrial stem cells injected into the brains of mice with a laboratory-induced form of Parkinson's disease appeared to take over the functioning of brain cells eradicated by the disease. The finding raises the possibility that women with Parkinson's disease could serve as their own stem cell donors. Similarly, because endometrial stem cells are readily available and easy to collect, banks of endometrial stem cells could be stored for men and women with Parkinson's disease. ... In the current study, the researchers generated stem cells using endometrial tissue obtained from nine women who did not have Parkinson's disease and verified that, in laboratory cultures, the unspecialized endometrial stem cells could be transformed into dopamine-producing nerve cells like those in the brain. The researchers also demonstrated that, when injected directly into the brains of mice with a Parkinson's-like condition, endometrial stem cells would develop into dopamine-producing cells. ... stem cells derived from endometrial tissue appear to be less likely to be rejected than are stem cells from other sources."

View the Article Under Discussion: http://www.sciencedaily.com/releases/2010/05/100506141608.htm

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

Autophagy is important in determining life span, probably because of its role in clearing out damaged mitochondria (a process known as mitophagy) before they can cause other forms of harm. Here is evidence for that view in the form of a link between Parkinson's disease and autophagy: "Mutations that cause Parkinson's disease prevent cells from destroying defective mitochondria ... Defects in the ubiquitin ligase Parkin are linked to early-onset cases of this neurodegenerative disorder. The wild-type protein promotes the removal of impaired mitochondria by a specialized version of the autophagy pathway called mitophagy, delivering mitochondria to the lysosomes for degradation. Mitochondria are often dysfunctional in Parkinson's disease ... cells expressing mutant forms of Parkin failed to clear their mitochondria after the organelles were damaged. Different mutations blocked mitophagy at distinct steps: mitochondria accumulated in the perinuclear region of cells expressing Parkin lacking its ubiquitin ligase activity, for example. The researchers found that ubiquitination of defective mitochondria by Parkin normally recruits the autophagy proteins HDAC6 and p62 to clear these mitochondrial aggregates. ... The clearance of defective mitochondria is therefore similar to the removal of damaged proteins, another autophagic process that goes wrong in Parkinson's disease resulting in the accumulation of toxic protein aggregates. Both pathways rely on microtubules, HDAC6, and p62, [providing] a common link between the two main features of the neurodegenerative disorder."

View the Article Under Discussion: http://www.eurekalert.org/pub_releases/2010-05/rup-mtc050610.php

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

From TechNewsWorld: "During his homily this Easter, Pope Benedict argued that medical science, in trying to defeat death, is leading humanity toward likely condemnation. It's a position at odds with the value of life, one that the Church will likely revise years from now, replaying the institution's embarrassment over censoring Galileo. ... If scientists are successful in finding techniques to rebuild cartilage, repair organs, and cure cancer, people will indeed be living longer - but they will also be healthier, more energetic and youthful. Health-extension, when it happens, will allow people to live longer, better. Consider that 60-year-olds today are not in the same shape as their counterparts were in the 1800s or 1900s. As humans discovered how to take better care of themselves, through improved nutrition, the use of antibiotics and other techniques, 'chronological age' became less synonymous with 'biological age.' That is, many of today's 60-year-olds act and feel much younger than one might expect. The average human life expectancy today is close to 80 years but in 1850, it was 43 years, and in 1900 it was 48 years. One can imagine someone in 1850 arguing that doubling life expectancy would be terrible, because innovation might be at risk and there would be more old people around. But would anyone today say they are sorry that science made it possible to live longer and healthier lives?"

View the Article Under Discussion: http://www.technewsworld.com/story/Galileo-20-Here-Comes-Another-Apology-69876.html

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

A detailed examination of recent progress from the SENS Foundation: "Recent years have seen both substantial progress, and significant frustration, in the preferred regenerative engineering approach to the treatment and prevention of Alzheimer's disease (AD), and the eventual regeneration of genuinely youthful cognitive function: immunotherapeutic clearance of beta-amyloid (AmyloSENS). ... results appear to many to commend an earlier window of opportunity for intervention, before concomitant [damage] and neuronal losses have made the removal of beta-amyloid alone insufficient for cognitive rescue. Early intervention might also maximize the therapeutic window for vaccination, preventing the burden of beta-amyloid neuropathology from ever reaching levels so high as to interact with other forms of aging damage in already frail and immunosenescent people." Present work on immune therapies for clearing unwanted biochemical junk from the body looks promising - there is every sign that today's advances will broaden into a general technology platform for this purpose. Researchers will be able to develop therapies that can be applied incrementally throughout life to remove the age-related gunk like beta-amyloid before it rises to dangerous levels.

View the Article Under Discussion: http://www.sens.org/node/757

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

There has been interest in extending increasing telomerase expression as a means to slow aging for some years. The available tools other than gene therapy are sparse on the ground, however. Telomerase extends telomere length, the caps of repeating DNA sequences at the ends of chromosomes that shorten with each cell division. Telomerase may have other roles that more directly impact aging, however, such as an influence on mitochondrial function.

Shorter telomeres in at least some tissues correlate with stress and ill health and aging, but this is a very dynamic system - average telomere length can change in either direction on a short time scale. It is far from clear that progressively shorter telomere length is a cause of aging rather than just a reflection of other changes and damage, and the same goes for natural variations in levels of telomerase in the body. While increasing expression of telomerase is shown to extend life in mice, that may or may not have anything to do with telomere length, and mouse telomerase biology is quite different from that of humans.

So all this said, it was only a matter of time before researchers evaluated all the existing approved drugs for treatment of age-related conditions to see if any of them altered telomerase activity. There are regulatory incentives to beware of here, however, in that it is much cheaper for research institutions to try to find marginal new uses of already approved drugs than to work on new and radically better medical technologies that would then have to go through the exceedingly and unnecessarily expensive approval process. So don't expect anything of great practical use to result from this:

Not only do statins extend lives by lowering cholesterol levels and reducing the risks of cardiovascular disease, but new research [suggests] that they may extend lifespans as well. Specifically, statins may reduce the rate at which telomeres shorten, a key factor in the natural aging process. This opens the door for using statins, or derivatives of statins, as an anti-aging therapy. "By telomerase activation, statins may represent a new molecular switch able to slow down senescent cells in our tissues and be able to lead healthy lifespan extension."

To make this discovery, Paolisso and colleagues worked with two groups of subjects. The first group was under chronic statin therapy, and the second group (control), did not use statins. When researchers measured telomerase activity in both groups, those undergoing statin treatment had higher telomerase activity in their white blood cells, which was associated with lower telomeres shortening along with aging as compared to the control group. This strongly highlights the role of telomerase activation in preventing the excessive accumulation of short telomeres.

"The great thing about statins is that they reduce risks for cardiovascular disease significantly and are generally safe for most people. The bad thing is that statins do have side effects, like muscle injury. But if it is confirmed that statins might actually slow aging itself - and not just the symptoms of aging - then statins are much more powerful drugs than we ever thought."

Link: http://www.eurekalert.org/pub_releases/2013-08/foas-sms082913.php

Source:
https://www.fightaging.org/archives/2013/08/statin-use-correlates-with-higher-telomerase-activity.php

Cytomegalovirus (CMV) is one of the less immediately harmful members of the family of herpesviruses. It is very prevalent: most people have it in their system by the time they are old, but probably never even noticed, as the symptoms for a healthy individual are essentially nonexistent. Nonetheless like all herpesviruses CMV is very successful at remaining within the body after initial exposure, establishing a life-long infection despite the best efforts of the immune system to get rid of it. The recurring campaigns waged against CMV by your immune cells appear to have a long-term cost: we have evolved to support a given number of immune cells as adults, and as ever more of those immune cells become specialized to a specific pathogen, such as CMV, there is ever less space left in the inventory for cells that can tackle new threats or keep up with all the other jobs of the immune system, such as destroying precancerous and senescent cells.

If you eye the publications of an open access journal like Immunity and Ageing, you'll see a steady flow of papers looking at the role of CMV in age-related immune system decline, a fair-sized component of the frailty of old age. There are a range of possible approaches to this problem, but the most direct and potentially effective don't actually involve doing anything about CMV itself. Instead there are proposals to either add large numbers of new, fresh, and capable immune cells to the body or eliminate the CMV-specialized cells to free up space. Both of these approaches are quite near-term: only a a couple of years would be needed to develop a viable prototype therapy from where we are now, were a research group fully funded and tasked with the effort. Both the ability to culture immune cells and the ability to destroy specific cells in the body based on their surface markers are progressing rapidly.

Some research groups are working on a vaccine for CMV - but a successful vaccine won't do much good for those high percentage of adults in much of the world who have been infected for a long time. Their immune systems are already badly misconfigured as a result of the extended exposure. So tackling CMV isn't a good enough approach on its own, as it only stops the very slow pace of ongoing harm.

Here is a paper to suggest that the progressive disarray in the immune system caused by CMV starts early, even while young.

Rudimentary signs of immunosenescence in Cytomegalovirus-seropositive healthy young adults

Ageing is associated with a decline in immune competence termed immunosenescence. In the elderly, this process results in an accumulation of differentiated 'effector' phenotype memory T cells, predominantly driven by Cytomegalovirus (CMV) infection.

Here, we asked whether CMV also drives immunity towards a senescent profile in healthy young adults. One hundred and fifty-eight individuals (age 21?±?3 years, body mass index 22.7?±?2.7) were assessed for CMV serostatus, the numbers/proportions of CD4+ and CD8+ late differentiated/effector memory cells, plasma interleukin-6 (IL-6) and antibody responses to an in vivo antigen challenge (half-dose influenza vaccine). Thirty percent (48/158) of participants were CMV+.

A higher lymphocyte and CD8+ count and a lower CD4/CD8 ratio were observed in CMV+ people. Eight percent (4/58) of CMV+ individuals exhibited a CD4/CD8 ratio of less than 1.0, whereas no CMV- donor showed an inverted ratio. The numbers of late differentiated/effector memory cells were?~fourfold higher in CMV+ people. Plasma IL-6 was higher in CMV+ donors and showed a positive association with the numbers of CD8+CD28- cells. Finally, there was a significant negative correlation between [vaccine response and the levels of CMV particles present]. This reduced vaccination response was associated with greater numbers of total late differentiated/effector memory cells.

This study observed marked changes in the immune profile of young adults infected with CMV, suggesting that this virus may underlie rudimentary aspects of immunosenescence even in a chronologically young population.

Source:
https://www.fightaging.org/archives/2013/08/measuring-the-impact-of-cytomegalovirus-in-younger-people.php

More evidence for the benefits of exercise: "Researchers from the University of Washington conducted a six-month clinical trial with 33 participants, 17 of whom were women. All showed early signs of Alzheimer's disease and were between the ages of 55 and 85. The experiment participants underwent a six-month intensive aerobic training program, spending 45 minutes to an hour four times each week on a stationary bicycle or treadmill. At the end of the six months, the participants saw improvement in mental agility, while the control group showed no improvement. Researchers are planning further studies to conduct larger and longer duration trials, following volunteers for years instead of months, for more conclusive data as to whether exercise can prevent full-blown cases of Alzheimer's. ... Other similar studies have been conducted, where researchers have measured the health benefits of resistance training for women between the ages of 65 and 75 who are most at risk for developing Alzheimer's. In one study, after one year of training, women who had completed the training showed better scores on mental acuity and conflict resolution tests than those who didn't."

View the Article Under Discussion: http://www.cavalierdaily.com/2010/04/21/remember-to-exercise-exercise-to-remember/

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

I had somehow missed this event from earlier in the year, a provocative (by mainstream standards) ad campaign mounted by a portion of the insurance industry: "The First Person To Live To 150 Is Alive Today." I take the existence of such a campaign as a sign of progress in ongoing efforts to spread the twofold message that (a) much longer lives are possible in the future, and (b) it is necessary to support the research process in order to make this happen soon enough to matter to you and I. Most of the children born today in wealthier parts of the world will have the opportunity to live for centuries at the very least, but the odds of people presently in mid-life are far more dependent on the pace of medical progress, and whether or not the right research strategies are nurtured.

By the side of an expressway the other afternoon, I saw a billboard paid for by Prudential, the big insurance and financial-services company. The message, in letters large enough that no motorist zipping by could miss them: "The First Person To Live To 150 Is Alive Today."

For centuries, scientists have been debating theories about just how long, with proper health care and judicious personal habits, the human lifespan can extend. In recent years, the 150 number has been up for discussion. Some have scoffed at that prospect, but insurance-company actuaries and retirement-planning accountants are not known for wacky practical jokes - they are as somber-eyed as funeral directors as they calculate just how big a risk they run while writing policies for their customers of various ages - so the sight of that Prudential billboard was a little jarring.

I contacted Prudential's corporate headquarters, and the company forwarded to me a table of federal statistics showing the lengthening average lifespans in the U.S. over the past 80 or so years. In 1930, the average life expectancy (measured at birth) of Americans was 59.7 years. By 1940, it had grown to 62.9. 1950: 68.2. 1960: 69.7. 1970: 70.8. 1980: 73.7 1990: 75.4. 2000: 77. 2010: 78.7.

Whether infants born today are entering a world in which 150th birthdays will eventually become if not common then at least possible, the thought raises separate issues for insurance and financial-planning firms than it does for the rest of us. For those companies, the prospect provides marketing opportunities. But for everyone else, it prompts the vexing question: Would you really want to live that long?

Link: http://www.cnn.com/2013/06/23/opinion/greene-living-to-150

Source:
https://www.fightaging.org/archives/2013/08/signs-of-progress-insurers-talk-of-radical-life-extension.php

There are many comparatively simple genetic alterations that enable animals of various different laboratory species to live between 10% to 60% longer. These are changes to the operation of metabolism: perhaps more autophagy, perhaps less fat tissue, perhaps fat tissue that behaves slightly less maliciously, perhaps a more resilient immune system, and so forth. The list is long and getting longer with each passing year as researchers continue to investigate the genetics of aging and longevity.

Here is a question: if all these changes are so simple, just minor genetic alterations, how is it that evolution failed to get there first? Why is it that researchers can alter the mouse genome in many different ways to extend the lives of laboratory mice? Why is the local optimal evolved state of the modern mouse short-lived in comparison to a great many close, easily-reached neighboring states?

The answer to these questions is that additional longevity is only one of many possible advantages to be obtained in evolutionary competition, and probably not a terribly good advantage in the grand scheme of things. In theory, and if individuals successfully evade natural hazards and predators, a longer life span means that a lineage can outbreed its competitors over time. Judging by the fact that very few species are unusually long-lived in comparison to their peers, however, we might conclude that longevity is only rarely more beneficial than other strategies for evolutionary success.

When researchers examine long-lived mutant mice, worms, and other short-lived species, they see signs that these lineages would be outmatched in the wild. Minor genetic changes to enhance longevity, even ones such as improved cellular maintenance that seem wholly beneficial, are not free. They come with attached costs in terms of success in the only game that matters over evolutionary time, which is the competition to propagate copies of your genome.

Hormesis and longevity with tannins: Free of charge or cost-intensive?

Hormetic lifespan extension is, for obvious reasons, beneficial to an individual. But is this effect really cost-neutral? To answer this question, four tannic polyphenols were tested on the nematode Caenorhabditis elegans. All were able to extend the lifespan, but only some in a hormetic fashion.

Additional life trait variables including stress resistance, reproductive behavior, growth, and physical fitness were observed during the exposure to the most life extending concentrations. These traits represent the quality of life and the population fitness, being the most important parameters of a hormetic treatment besides lifespan. Indeed, it emerged that each life-extension is accompanied by a constraining effect in at least one other endpoint, for example growth, mobility, stress resistance, or reproduction. Thus, in this context, longevity could not be considered to be attained for free and therefore it is likely that other hormetic benefits may also incur cost-intensive and unpredictable side-effects.

Laboratory selection for increased longevity in Drosophila melanogaster reduces field performance

Drosophila melanogaster is frequently used in ageing studies to elucidate which mechanisms determine the onset and progress of senescence. Lines selected for increased longevity have often been shown to perform as well as or superior to control lines in life history, stress resistance and behavioural traits when tested in the laboratory. Functional senescence in longevity selected lines has also been shown to occur at a slower rate.

However, it is known that performance in a controlled laboratory setting is not necessarily representative of performance in nature. In this study the effect of ageing, environmental temperature and longevity selection on performance in the field was tested. Flies from longevity selected and control lines of different ages (2, 5, 10 and 15 days) were released in an environment free of natural food sources. Control flies were tested at low, intermediate and high temperatures, while longevity selected flies were tested at the intermediate temperature only. The ability of flies to locate and reach a food source was tested.

Flies of intermediate age were generally better at locating resources than both younger and older flies, where hot and cold environments accelerate the senescent decline in performance. Control lines were better able to locate a resource compared to longevity selected lines of the same age, suggesting longevity comes at a cost in early life field fitness, supporting the antagonistic pleiotropy theory of ageing.

If you are a member of a species with access to advanced medical technology, none of this much matters any more, of course. The future of longevity under those circumstances is determined by progress in technology rather than evolution: natural selection just sets the scene, and ensures that we are all dissatisfied with the hand we have been dealt.

Source:
https://www.fightaging.org/archives/2013/08/the-cost-of-living-longer-even-in-good-health.php

A general interest article on transhumanist visions of the future and immortality in the sense of the continued repair and reversal of aging through medical technology: "Immortality could be sneaking up faster than we can believe. Barely a month goes by without some new advance in organ replacement, and a recent operation to replace a boy's windpipe with one generated from his own stem cells was called 'embarrassingly simple' by the specialist in charge. Further breakthroughs could be made by the SENS Foundation, led by the radical immortalist Aubrey de Grey, with a brutally simple plan to give humans an unbeatable protection against cancer. This involves limiting human cells' ability to divide at cancerous levels, with regular top-ups from externally grown cells replacing worn-out tissue. If these technologies can hold to their promise, biological immortality, perhaps the most cherished goal of the transhumanists, may be with us in a few decades. A loose grouping of scientists, philosophers and sympathisers, with organisations such as the Oxford Future of Humanity Institute and Humanity+, transhumanists urge human progress through radical technological enhancement. With regards to immortality, I'm certainly a sympathiser: if a dictator was murdering tens of millions of people right across the world, we'd gladly do anything to overthrow him. And yet ageing, as eloquently put by the transhumanist philosopher Nick Bostrom, is a tyrant that kills us by the cartload - and what do we do to stop it?"

View the Article Under Discussion: http://www.guardian.co.uk/commentisfree/2010/apr/15/transhumanism-biological-immortality

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

Cryonics is the low-temperature storage of the brain on clinical death, preserving the fine structure of the mind for a future of more advanced technologies. It is a vitally important industry for all that it is overlooked by most of the world and rejected as an alternative to the grave by nearly everyone who has actually heard of it and considered it. Even under the most optimistic plausible course of development for rejuvenation biotechnology, billions of people will die due to degenerative aging before it can be brought under medical control. Yet the technology exists today to preserve those people for a future in which they can be restored to active life through applications of advanced medical nanotechnology.

So there is dead and there is dead and gone. The grave means dead and gone - there is no future technology that can restore you once the pattern of your mind has vanished from the world. But if your brain and the structure encoding the data of your mind is preserved then you are only dead until such time as you can be safely restored. Perhaps that will never happen, but the odds are not zero, as is the case for the traditional options of burial, cremation, and so forth.

In a better world, cryonics would be a vast industry with efficiencies of scale, offering preservation at a far lower cost than it does today. Cryopreservation would be the default traditional option at the end of life, and most people would go into the future with some chance at living again. Alas, we do not live in that world. We live in the world in which people flock to certain oblivion, in which supporting scientific work on human rejuvenation is a hard sell, and in which cryonics after four decades of existence remains a very small niche industry.

The Singularity Weblog author recently visited cryonics provider Alcor for a behind the scenes tour and to interview CEO Max More. He was kind enough to upload some of the resulting video to YouTube.

My Video Tour of Alcor and Interview with CEO Max More

Last month I had the privilege of visiting Max More at the Alcor Life Extension Foundation. Alcor is a non-profit organization founded in 1972 and located in Scottsdale, Arizona. It is the world leader in cryonics, cryonics research, and cryonics technology. [Cryonics is the science of using ultra-cold temperature to preserve human life with the intent of restoring good health when technology becomes available to do so.]

During our visit CEO Dr. More walked us through the Alcor facilities as well as the process starting after clinical death is proclaimed, through the cooling of the body and its vitrification, and ending in long term storage.

After our video tour of Alcor CEO Max More was kind enough to take another 25 minutes and answer some questions. During our conversation with Max we discuss: general affordability and prices for Alcor; long-distance membership and why minimizing cooling delays is critical for optimum body preservation; preserving pets; chemical brain preservation; the importance of preserving the neuron's micro-tubules; the potential for X-prize-type of a competition for minimizing tissue damage and improving preservation; the relationship between cryonics and transhumanism.

My favorite quote that I will take away from this interview with Max More is: "Cryonics is critical care medicine taken to the next step."

Source:
https://www.fightaging.org/archives/2013/08/a-video-tour-of-alcor-and-interview-with-max-more.php

The interaction between genes, metabolism, and natural variations in longevity is an enormously complex space. This complexity is why efforts to slow aging by altering metabolism are doomed to be a very slow, very expensive undertaking, one which is unlikely to produce meaningful results within the next few decades. It will be much easier to instead identify the forms of damage that cause aging and periodically repair them without trying to otherwise change our genes or metabolic processes. We know the metabolism we have when young works just fine, so the focus of longevity science should be on reverting the limited set of changes in and around cells that differentiate old tissues from young tissues.

Here is a good short summary of the current state of knowledge of genetics and longevity, illustrating that researchers are really only just at the outset of a very long process of obtaining a full or at least actionable understanding:

Longevity and healthy aging are among the most complex phenotypes studied to date. The heritability of age at death in adulthood is approximately 25%. Studies of exceptionally long-lived individuals show that heritability is greatest at the oldest ages.

Linkage studies of exceptionally long-lived families now support a longevity locus on chromosome 3; other putative longevity loci differ between studies. Candidate gene studies have identified variants at APOE and FOXO3A associated with longevity; other genes show inconsistent results. Genome-wide association scans (GWAS) of centenarians vs. younger controls reveal only APOE as achieving genome-wide significance (GWS); however, analyses of combinations of SNPs or genes represented among associations that do not reach GWS have identified pathways and signatures that converge upon genes and biological processes related to aging. The impact of these SNPs, which may exert joint effects, may be obscured by gene-environment interactions or inter-ethnic differences.

GWAS and whole genome sequencing data both show that the risk alleles defined by GWAS of common complex diseases are, perhaps surprisingly, found in long-lived individuals, who may tolerate them by means of protective genetic factors. Such protective factors may 'buffer' the effects of specific risk alleles. Rare alleles are also likely to contribute to healthy aging and longevity.

Epigenetics is quickly emerging as a critical aspect of aging and longevity. Centenarians delay age-related methylation changes, and they can pass this methylation preservation ability on to their offspring. Non-genetic factors, particularly lifestyle, clearly affect the development of age-related diseases and affect health and lifespan in the general population. To fully understand the desirable phenotypes of healthy aging and longevity, it will be necessary to examine whole genome data from large numbers of healthy long-lived individuals to look simultaneously at both common and rare alleles, with impeccable control for population stratification and consideration of non-genetic factors such as environment.

Link: http://www.ncbi.nlm.nih.gov/pubmed/23925498

Source:
https://www.fightaging.org/archives/2013/08/the-current-state-of-knowledge-of-genetics-and-longevity.php

Mammalian (or mechanistic, depending on who you ask) target of rapamycin (mTOR) is the most likely candidate for the next round of billion-dollar research funding devoted to the search for drugs that can slow aging. It will be a repeat of the overhyped and ultimately largely futile interest in sirtuin research, which generated knowledge but nothing of real practical application, except that this time there is far more compelling evidence that manipulation of mTOR actually extends life in laboratory animals. Though as always, there are those who believe that this is not in fact the case - that mTOR alteration only reduces cancer risk, rather than impacting the processes of aging per se. Just as resveratrol and resveratrol-derivatives are the compounds of choice for those investigating sirtuin biology, so rapamycin and rapamycin-derivatives are the compounds of choice for research groups focused on manipulating mTOR and its related signaling networks. I would imagine that we're in for another decade or so of overhyped claims and public and research community interest in what is in fact an inefficient, expensive, and time-consuming path towards only slightly extending healthy life.

Drugs to slow aging through alterations to metabolism are not the path to radical life extension. Slowing aging does nothing for people already old. The research community should focus instead on rejuvenation through therapies that repair and remove the cellular damage that causes aging, an approach that can actually meaningfully help the aged when realized. For all that rejuvenation is the obviously superior research strategy, however, it's taking time to convince the world of that truth. Time spent on trying to slow aging is little different in outcome to time spent investigating the details of aging but choosing to do nothing about it: a few years here and there, and nothing that is as effective as simple exercise and calorie restriction. There's no such thing as useless knowledge in the long term, but we already know enough to work effectively on human rejuvenation.

The new study quoted below will no doubt bolster the prospects of those groups presently raising funds for attempts to slow aging or further develop drug candidates derived from rapamycin. While looking at the results, however, you might compare them with plain old calorie restriction in mice, something that can produce twice the extension of healthy life shown here.

Mutant Mice Live Longer

MTOR is a kinase involved in myriad cellular processes, from autophagy to protein synthesis. Genetic studies of TOR in other organisms, such as yeast and flies, have implicated a role for the enzyme in lifespan. In mammals, however, mTOR is required for survival, making a knockout mouse model unfeasible. So the National Heart, Lung and Blood Institute's Toren Finkel and his colleagues decided to use a mouse in which transcription was only partially disrupted, reducing the levels of mTOR to about 25 percent of the normal amount.

All else being equal, the researchers found that normal mice typically lived 26 months, while those with less mTOR survived around 30 months. Finkel said the increase in lifespan was greater than other researchers have seen using the immunosuppressant rapamycin to inhibit mTOR. It's possible that having mTOR reduced beginning in the womb, rather than at middle age, could explain the disparity. Additionally, this new mutant affected the levels of both forms of mTOR - mTORC1 and mTORC2 complexes - rather than preferentially impacting one, as rapamycin would.

The paper on this research is open access, so head on over and take a look. I think you'll find it interesting. In particular note the author's cautions regarding the size of the life extension effect and the life span of the control mice in the discussion section: the number of mice used isn't large, and it's possible that the controls were just randomly a slightly short-lived group.

Increased Mammalian Lifespan and a Segmental and Tissue-Specific Slowing of Aging after Genetic Reduction of mTOR Expression

We analyzed aging parameters using a mechanistic target of rapamycin (mTOR) hypomorphic mouse model. Mice with two hypomorphic (mTOR?/?) alleles are viable but express mTOR at approximately 25% of wild-type levels. These animals demonstrate reduced mTORC1 and mTORC2 activity and exhibit an approximately 20% increase in median survival. While mTOR?/? mice are smaller than wild-type mice, these animals do not demonstrate any alterations in normalized food intake, glucose homeostasis, or metabolic rate. Consistent with their increased lifespan, mTOR?/? mice exhibited a reduction in a number of aging tissue biomarkers. Functional assessment suggested that, as mTOR?/? mice age, they exhibit a marked functional preservation in many, but not all, organ systems. Thus, in a mammalian model, while reducing mTOR expression markedly increases overall lifespan, it affects the age-dependent decline in tissue and organ function in a segmental fashion.

Source:
https://www.fightaging.org/archives/2013/08/decreased-mtor-expression-provides-20-mean-life-span-extension-in-mice.php

Building patches for damaged hearts is a popular implementation in tissue engineering at the moment: it's an achievable stepping stone on the way to more complex goals, such as the creation of entire organs starting from only a patient's stem cells, something that still lies in the future. Progress towards a long-term goal in any field requires useful intermediary products, as they help pull in the greater support and funding needed for the next phase of research and development.

When heart cells die from lack of blood flow during a heart attack, replacing those dead cells is vital to the heart muscle's recovery. But muscle tissue in the adult human heart has a limited capacity to heal, which has spurred researchers to try to give the healing process a boost. Various methods of transplanting healthy cells into a damaged heart have been tried, but have yet to yield consistent success in promoting healing.

Now, [researchers] have developed a patch composed of structurally modified collagen that can be grafted onto damaged heart tissue. Their studies in mice have demonstrated that the patch not only speeds generation of new cells and blood vessels in the damaged area, it also limits the degree of tissue damage resulting from the original trauma. The key [is] that the patch doesn't seek to replace the dead heart-muscle cells. Instead, it replaces the epicardium, the outer layer of heart tissue, which is not muscle tissue, but which protects and supports the heart muscle, or myocardium.

The epicardium - or its artificial replacement - has to allow the cell migration and proliferation needed to rebuild damaged tissue, as well as be sufficiently permeable to allow nutrients and cellular waste to pass through the network of blood vessels that weaves through it. The mesh-like structure of collagen fibers in the patch has those attributes, serving to support and guide new growth. Because the patch is made of acellular collagen, meaning it contains no cells, recipient animals do not need to be immunosuppressed to avoid rejection. With time, the collagen gets absorbed into the organ.

Link: http://www.eurekalert.org/pub_releases/2013-08/sumc-scp082613.php

Source:
https://www.fightaging.org/archives/2013/08/a-collagen-patch-to-spur-heart-tissue-repair.php

There is no technology so beneficial that someone somewhere isn't thinking about how to use it to hurt people. That even holds true for means of rejuvenation, ways to eliminate the vast and terrible cost of degenerative aging, all of the suffering, the tens of millions of deaths each and every year. Some people look at the possibilities for near future human rejuvenation and think "I've figured out a way to use this to more effectively hurt the groups of people that we don't like."

Some argue that retributive punishment (reactionary punishment, such as imprisonment) should be replaced where possible with a forward-looking approach such as restorative justice. I imagine, however, that even opponents of retributive justice would shrink from suggesting that [the worst of offenders] should escape unpunished. I assume - in line with the mainstream view of punishment in the UK legal system and in every other culture I can think of - that retributive punishment is appropriate in [some cases].

Within the transhumanist movement, the belief that science will soon be able to halt the ageing process and enable humans to remain healthy indefinitely is widespread. Dr Aubrey de Grey, co-founder of the anti-ageing SENS Research Foundation, believes that the first person to live to 1,000 years has already been born. The benefits of such radical lifespan enhancement are obvious - but it could also be harnessed to increase the severity of punishments. In cases where a thirty-year life sentence is judged too lenient, convicted criminals could be sentenced to receive a life sentence in conjunction with lifespan enhancement. As a result, life imprisonment could mean several hundred years rather than a few decades. It would, of course, be more expensive for society to support such sentences. However, if lifespan enhancement were widely available, this cost could be offset by the increased contributions of a longer-lived workforce.

When the state enforces a monopoly on criminal dispute resolution, as is the case in most regions of the world these days, the only interests served are those of the state employees and appointees involved. Even in legitimate cases you end up with the worst of all worlds: the system remains based upon serving a desire for vengeance and appeasing the mob, imprisonment (as opposed to banishment or outlawing) removes the ability for an offender to work towards restitution, and those with the greatest interest in obtaining justice and resolution are cut out of the decision-making process. There is worse, however. The methods and traditions created for the worst offenders are soon enough applied to everyone without sufficient power and influence to buy their way clear. Modern systems of state justice are terrible impersonal engines, set upon expansion, and all too quickly used for self-empowerment and suppression of dissent by politicians and bureaucrats.

Link: http://blog.practicalethics.ox.ac.uk/2013/08/enhanced-punishment-can-technology-make-life-sentences-longer/

Source:
https://www.fightaging.org/archives/2013/08/and-now-for-something-reprehensible.php