At root, medicine is driven by the urge remain alive. It is a process of engineering the means to prevent death, and so setting out to deliberately create greater longevity by tackling the root causes of aging - rather than addressing named diseases, one by one - is no more than the logical next step in this process. We know more than enough to get started down this path, and there are some few organizations working on it even today, though far from enough and with far from enough funding.

Consider a world with the means to prevent aging - say, though a package of therapies that a person undergoes every twenty years or so. Infusions of fresh stem cell populations, engineered enzymes to degrade metabolic waste products that build up in and around cells to impair their function, some form of mitochondrial DNA repair, culling excess memory T cells, and so on. These therapies prevent and reverse the build up of damage, allowing a body to continue in good health indefinitely. There is no good reason for them to be any more expensive than your average run of clinical treatments today: they would require little time from a physician, and would operate in much the same way for everyone, allowing economies of scale in production and distribution.

In such a society, all of the pressures associated with the short span of life we presently enjoy evaporate. We are so steeped in that omnipresent pressure of time that it's somewhat hard to envisage what a society without it would look like. Every strategic decision that we make in the course of our lives is based on time - that we have ever less of it remaining, the clock is ticking, and have only a few shots at getting anything significant accomplished. It requires a decade to become truly talented in any particular profession or skill, for example, and at least a few years to figure out whether not we can follow through to that level. That is a vast investment of time when we only have a few decades in which we are at our prime. The same goes for careers and relationships of any significance. We are pressured and choices have great weight precisely because we must forever give up an ocean of possibilities in order to swim in any particular pool.

There is a related school of thought among those opposed to engineering longevity: they say that the pressures of time created by the fact that we age to death due to our inadequate medical technology are a good thing. To me this has the look of rushing to justify what is, regardless of what might be, but they argue that the industry of individuals and humanity as a whole requires the deadline of dying; that without it, no-one would accomplish anything. They look upon the unending holocaust of death and destruction caused by aging - 100,000 lives every day, all they knew, all they could accomplish in the future, all they might have done, erased - and say it is necessary.

This is a hideous nonsense, serving to illustrate that little but a veneer separates us from the barbarians who actively slaughtered millions in past decades. It is true that rapid progress is very necessary in today's world - but we need it because we are dying, and the only way to save ourselves is through technological progress. The faster the better, every increment of speed representing countless lives that might be saved on some future date. If more people were more aware and more interested in doing something about this, we might move faster yet towards the biotechnologies of rejuvenation. Unfortunately, for all that each and every human life is shaped completely by the foreknowledge of future disability and death, all too few are willing to help change this state of affairs.

But so what if the medical technologies that can prevent death by aging make our societies slower-paced, more considered, less energetic? I'm not of the mind that this is a terrible thing - free-wheeling use of a resource is characteristic of wealth, and when we are wealthy in time, we will have the luxury to use it in ways that presently make little sense, or are called wasteful. Caring about waste is a sign of poverty, a sign that we don't have enough of whatever we worry about wasting, which in turn suggests we should do all we can to accumulate more of it. Besides, I don't for one moment believe that the slowing of economic engines and technological progress will in fact happen as feared by those who advocate for the continuation of mass death and suffering. There are all sorts of economic pressures upon human action that have next to nothing to do with aging and our current all-too-short span of life: consider the shifting desires for security, food, property, knowledge, and novelty, for example. The timescales on which those urges operate will not much change in an ageless society, as people will still have the same human nature as exists today. There will continue to be dynamic and ever-changing industries devoted to keeping people fed, clothed, and entertained.

These responses to irrational fears are, at the bottom line, unnecessary to some degree. 100,000 people died today of a cause that we can do something about. Tens of millions die every year, and hundreds of millions more suffer terribly on their way to that end. There is no argument that can possibly outweigh the need to address what is by far the greatest cause of death, suffering, and loss in the world - yet, for some strange combination of reasons, many people keep trying to find one.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Progress towards a non-invasive test for Alzheimer's disease: "Reliability and failure to replicate initial results have been the biggest challenge in this field. We demonstrate here that it is possible to show consistent findings. ... [Researchers] measured the levels of 190 proteins in the blood of 600 study participants [including] healthy volunteers and those who had been diagnosed with Alzheimer's disease or mild cognitive impairment (MCI). MCI, often considered a harbinger for Alzheimer's disease, causes a slight but measurable decline in cognitive abilities. A subset of the 190 protein levels (17) were significantly different in people with MCI or Alzheimer's. When those markers were checked against data from 566 people participating in the multicenter Alzheimer's Disease Neuroimaging Initiative, only four markers remained: apolipoprotein E, B-type natriuretic peptide, C-reactive protein and pancreatic polypeptide. Changes in levels of these four proteins in blood also correlated with measurements from the same patients of the levels of proteins [beta-amyloid] in cerebrospinal fluid that previously have been connected with Alzheimer's. The analysis grouped together people with MCI, who are at high risk of developing Alzheimer's, and full Alzheimer's. ... Though a blood test to identify underlying Alzheimer's disease is not quite ready for prime time given today's technology, we now have identified ways to make sure that a test will be reliable."

Link: http://www.eurekalert.org/pub_releases/2012-08/eu-btf080912.php

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

There are a great many theories of aging, and here is another for the pile from a researcher who leans towards aging as genetic programming rather than aging as accumulated damage: "The biological mechanisms at the heart of the aging process are a long-standing mystery. An influential theory has it that aging is the result of an accumulation of molecular damage, caused in particular by reactive oxygen species (ROS) produced by mitochondria. This theory also predicts that processes that protect against oxidative damage (involving detoxification, repair and turnover) protect against aging and increase lifespan. ... However, recent tests of the oxidative damage theory, many using the short-lived nematode worm Caenorhabditis elegans, have often failed to support the theory. This motivates consideration of alternative models. One new theory [proposes] that aging is caused by hyperfunction, i.e. over-activity during adulthood of processes (particularly biosynthetic) that contribute to development and reproduction. Such hyperfunction can lead to hypertrophy-associated pathologies, which cause the age increase in mortality. ... Here we assess whether the hyperfunction theory is at all consistent with what is know about C. elegans aging, and conclude that it is. In particular, during adulthood C. elegans show a number of changes that may reflect pathology and/or hyperfunction. Such changes seem to contribute to mortality, at least in some cases (e.g. yolk accumulation). ... Our assessment suggests that the hyperfunction theory is a plausible alternative to the molecular damage theory to explain aging in C. elegans."

Link: http://extremelongevity.net/2012/08/09/is-aging-due-to-hyperfunction/

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

For whatever reason, a number of public voices seem to be talking about immortality all of a sudden, largely meaning physical immortality in the sense of immunity to aging but vulnerability to fatal accidents. Topics ebb and flow like tides, I suppose, the signs of many hidden connections that underlie our culture - that grand conversation of innumerable threads held in the myriad communication channels available to us.

• Russian Mogul Soliciting Billionaires to Achieve Immortality
• Kurzweil Talks About Achievable Immortality On PBS NewsHour
• Do All Transhumanists Want Immortality? No? Why Not?
• We Talk To The Philosopher Being Given $5 Million To Study Immortality

It's a big project so it's hard to summarize to its core being but I'd say we're investigating two different kinds of immortality. One would be the possibility of living forever without ever dying. The main questions there are whether it's technologically plausible or feasible for us, either by biological enhancement such as those described by Ray Kurzweil, or by some combination of biological enhancement and uploading our minds onto computers in the future. I think another more interesting and important question is would we choose to be immortal in that sense, or does death and finitude give life meaning?

And so forth, repeated in the echo chamber. Immortality can be a useful term - such as on the occasions on which you want to plant a flag a long way out in the discussion and make waves. It is, I think, becoming less useful with time, however. So many people use it without meaning or with so many varied and half-thought meanings that it is, like "anti-aging", becoming more harmful than helpful. Too much baggage, too many charlatans of various types hitching their carts to the bandwagon.

Putting in serious time and thought on physical immortality - $5 million here and $5 million there adds up pretty quickly - seems to me to be premature. There is a great deal of work that lies between here and first generation rejuvenation biotechnology, something that will allow us to live additional decades in good health, never mind what comes after that. The rise and rapid obsolescence of many massive industries in medicine will happen over the next fifty years in order to extend the outer limits of human health and life span far beyond the present century-and-a-bit. Each of those churning engines of progress will see millions of individuals working in hundreds of competing companies, a world of intricate detail.

The result of all of that? Possibly humans that can live for two centuries or more before hitting as-yet unknown limits to presently envisaged biological repair technologies. This is a drop in the ocean of time. But that will give a hundred years of grace in which to work feverishly on the next generations of technology: replacements for biological systems, improving on the ways to repair and rebuild our cells, merging with our machines as those machines become ever smaller and more capable. The world of a century and a half from now will be as distant and strange and capable to us as our tools and society would seem to a 18th century peasant.

My point is that many transformative, world-sweeping changes brought by advancing technology will occur in the decades between now and even a mere hard-fought doubling of the human life span. We'll be starting in earnest to settle the Moon and Mars by then. Our machines will be able to think for themselves. Desktop and motile nanofactories will be capable of fabricating everything from houses to gene therapies from raw materials. A sea of historical and cultural manuscripts will be written on those changes, and still fail to easily capture the scope of the way in which the world changes.

And then it starts over again, ever building new and greater edifices as we push on to overcome the next set of limits to the human condition. All of this grand and complex near future of increasing longevity and massive change seems far more worthy of thought than immortality, given the length of the road between here and there, and how much has to be done to even start talking seriously about lives of tens of thousands of years.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Efforts continue to correlate longevity with the activity levels of specific genes: "MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression and play a critical role in development, homeostasis, and disease. Despite their demonstrated roles in age-associated pathologies, little is known about the role of miRNAs in human aging and longevity. ... We employed massively parallel sequencing technology to identify miRNAs expressed in B-cells from Ashkenazi Jewish centenarians, i.e., those living to a hundred and a human model of exceptional longevity, and younger controls without a family history of longevity. ... we discovered a total of 276 known miRNAs and 8 unknown miRNAs ranging several orders of magnitude in expression levels, a typical characteristics of saturated miRNA-sequencing. A total of 22 miRNAs were found to be significantly upregulated, with only 2 miRNAs downregulated, in centenarians as compared to controls. Gene Ontology analysis of the predicted and validated targets of the 24 differentially expressed miRNAs indicated enrichment of functional pathways involved in cell metabolism, cell cycle, cell signaling, and cell differentiation. A cross sectional expression analysis of the differentially expressed miRNAs in B-cells from Ashkenazi Jewish individuals between the 50th and 100th years of age indicated that expression levels of miR-363* declined significantly with age. Centenarians, however, maintained the youthful expression level. This result suggests that miR-363* may be a candidate longevity-associated miRNA.

Link: http://dx.doi.org/10.1186/1471-2164-13-353

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

A number of diverse lines of research and development will lead to new technologies that replace or repair organs. The present list looks much as follows:

• Electromechanical and blended biological-electromechanical systems: artificial hearts, prosthetic limbs and eyes, dialysis machines that contain cultured kidney tissue, and so forth.
• Repair of organs in situ using transplanted stem cells or stem cell signaling to spur regrowth that otherwise would not happen.
• Engineering of complete organs from a patient's own cells, such as through bioprinting.
• Decellularization to replace the cells in human donor tissue and organs in order to form patient-matched transplants.
• Xenotransplantation: the use of decellularized organs and tissues from animals, which provide the structure and chemical cues to allow repopulation with the patient's human cells.

A recent article at the Scientist looks at a couple of these lines of work - organ engineering versus xenotransplantation, both of which draw heavily upon the comparatively new techniques of decellularization in order to achieve new and better results, both in the laboratory and for patients in trials:

Today, the organ shortage is an even bigger problem than it was in the 1980s. ... he supply has stagnated despite well-funded attempts to encourage donations, and demand is growing, especially as the organs of a longer-lived population wear out.

Faced with this common problem, Vacanti and Cooper have championed very different solutions. Cooper thinks that the best hope of providing more organs lies in xenotransplantation - the act of replacing a human organ with an animal one. From his time in Cape Town to his current position at the University of Pittsburgh, he has been trying to solve the many problems that occur when pig organs enter human bodies, from immune rejection to blood clots. Vacanti, now at Massachusetts General Hospital, has instead been developing technology to create genetically tailored organs out of a patient's own cells, abolishing compatibility issues. "I said to myself: why can't we just make an organ?" he recalls.

In the race to solve the organ shortage, xenotransplantation is like the slow and steady tortoise, still taking small steps after a long run-up, while organ engineering is more like a sprinting hare, racing towards a still-distant finish line. Most of those betting on the race are backing the hare. Industry support has dried up for xenotransplantation after years of slow progress, leaving public funders to pick up the expensive tab. Stem cells, meanwhile, continue to draw attention and investment. But both fields have made important advances in recent years, and the likely winner of their race - or whether it will result in a draw - is far from clear.

...

Xenotransplants will always have to deal with an immune clash of some degree, so growing an organ that is perfectly matched to a patient would be preferable. The question is whether tissue-engineering technologies will reach that point before genetic engineering enables the first transgenic pig hearts or kidneys to be successfully installed in patients. Sachs says, "I consider xenotransplantation still the nearest-term, best hope for solving the organ shortage, but in the long run, I think tissue engineering will replace it."

There is also the matter of scale. Platt thinks that organ engineering is too costly to meet the needs of everyone waiting for a transplant. "You'd have to turn over the entire GDP of a country to accomplish that," he says. On the other hand, "I could get a pig for a couple of hundred dollars." But Macchiarini argues that organ engineering is in its infancy, and every advance improves efficiency and lowers cost. "What we did in 2008 in 6 months, we can now do in a few weeks," he says. "We do care about getting this to every patient." Vacanti adds that mass-producing artificial scaffolds will make organ engineering even more cost-effective. "When you scale them up, the bulk materials and manufacturing tech are extremely cheap," he says. "I think it's going to be cheaper than growing lots of pigs."

We shall see. The only sure thing in my book is that vigorous competition is good for both speeding progress and producing higher quality solutions. That is just as true in medicine as for every other field of human endeavor.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

There is no shortage of theories as to why women live longer than men - an apparently simple question, but one balanced on such a mountain of complex data and partial knowledge that it cannot be definitively answered at the present time. Here is another theory for the stack: "Mitochondria are inherited only from mothers, never from fathers, so there is no way to weed out mutations that damage a male's prospects. ... [Researchers] analysed the mitochondria of 13 different groups of male and female fruit flies. Mitochondria, which exist in almost all animal cells, convert food into the energy that powers the body. ... the results point to numerous mutations within mitochondrial DNA that affect how long males live, and the speed at which they age. ... Intriguingly, these same mutations have no effects on patterns of ageing in females. All animals possess mitochondria, and the tendency for females to outlive males is common to many different species. Our results therefore suggest that the mitochondrial mutations we have uncovered will generally cause faster male ageing across the animal kingdom. ... They suggest this is because there is no evolutionary reason for the faults that affect males to be picked up - because mitochondria are passed down by females. ... If a mitochondrial mutation occurs that harms fathers, but has no effect on mothers, this mutation will slip through the gaze of natural selection, unnoticed. Over thousands of generations, many such mutations have accumulated that harm only males, while leaving females unscathed."

Link: http://www.bbc.co.uk/news/health-19093442

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

We have a great deal more control over the age-related decline of the brain than was once thought - "use it or lose it", and the ability to affect change through challenging the mind. Yet it remains the case that new biotechnology and medicine will be required to get to where we want to be, a world without the risk of dementia, fuzzy memory, and slow cognition. Still, the plasticity of the aging brain is encouraging: "There is growing evidence that, beyond what was previously believed, the adult human brain is remarkably malleable and capable of new feats - even in the last decades of life. In fact, new experiences can trigger major physical changes in the brain within just a few days, and certain conditions can accelerate this physical, chemical and functional remodeling of the brain. ... We used to think that the brain was completely formed by development and its basic structure didn't change much in adults, but as research went on we discovered that wasn't true, at least in the cerebral cortex. We now know that an underlying portion of the brain called the thalamus, which feeds the cortex information from our senses, is also remarkably plastic. ... There is no evidence that there is any part of the adult brain that is not plastic. But studies indicate that some aspects of musical training, such as the ability to perceive temporal patterns, require the brain to be trained during early developmental periods when its primed for certain types of stimuli. For other aspects of musical development, such as the ability to perceive and repeat a sequence of tones, it's irrelevant whether you've had that experience and training early in life. ... The brain is plastic for life. The fundamental thing that determines how much [persons with brain disorders] will improve is the level of their initial impairment, but not their age."

Link: http://www.newswise.com/articles/researchers-find-the-brain-more-malleable-than-believed

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Some viruses show promise in terms of preferentially attacking cancer cells - but they can be engineered to be far more effective in the role of therapeutic agent: "Parvoviruses specifically kill cancer cells and are already in the clinical trial stage for treating malignant brain tumors. However, they can also infect normal cells - without doing any harm to them - so a large portion of viruses is lost during therapy. [Researchers] have now modified parvoviruses in such a way that they initially lose their ability to infect cells. In a second step, they equipped the viruses with a molecular key for infecting cancer cells. ... the researchers chose H1 parvoviruses, which normally infect rodents but are also infectious for human cells. H1 viruses kill tumor cells on the basis of their natural properties, i.e., their genetic material does not need to be modified for them to do so. ... The viruses exclusively destroy cancer cells. But with the same efficiency that they infect cancer cells, they also infect healthy cells. There they do not cause any damage and cannot replicate, but we lose a large portion of therapeutic viruses every time ... To solve this problem, the researchers [first] modified the genetic material of the virus in such a way that it loses its ability to infect cells. In a second step, this non-infectious virus was equipped with a molecular key for cancer cells. ... This is first evidence that it is basically possible to modify properties of H1 according to a plan. We will surely need several more attempts in order to target the viruses more specifically to cancer cells in the second step. We also already have ideas how to further enhance the infectious capacity and the potential to destroy cancer cells."

Link: http://www.kurzweilai.net/tailor-made-viruses-for-enhanced-cancer-therapy

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

A recent open access commentary by researcher Michael Rose and colleagues looks at the following question: what, exactly, is aging? Much like art, we might know it if we see it, but there's plenty of room for debate over the details.

What is Aging?

In 1991, the book Evolutionary Biology of Aging offered the following definition of aging: a persistent decline in the age-specific fitness components of an organism due to internal physiological deterioration (Rose, 1991). This definition has since been used by others a number of times. However, it was only a modest generalization of a definition proffered by Alex Comfort over three editions (1956-1979) of his key book The Biology of Senescence (Comfort, 1979): "a progressive increase throughout life, or after a given stadium, in the likelihood that a given individual will die, during the next succeeding unit of time, from randomly distributed causes."

...

Yet a mere definition does not necessarily tell a scientist what causally underlies the phenomenon that is so defined. The latter issue is much broader, implicitly raising fundamental scientific questions regarding mechanisms.

From here the piece heads off into a discussion of late life plateaus in aging, for example in flies where it is observed that the chance of death per unit time stops rising at advanced ages - in other words the flies stop aging by one definition of the term, left with a high but steady mortality rate. There are some arguments for this phenomenon to exist in humans, but the data is sparse and other results argue the opposite conclusion. Still, the researchers here argue that the demonstrated existence of this phenomenon in lower animals requires further thought to be directed towards how to define aging:

it appears that the cessation of aging occurs at the individual level, and is not just an artifact of population structure. Yet this is clearly paradoxical, if we think of the machinery of aging in terms of such physiological processes as steadily cumulative damage. If it is supposed that some process of cumulative damage or disharmony is supposed to underlie aging, why should that process abruptly stop at the very point, late in adult life, when it has greatly reduced the ability of the surviving individuals to sustain life and reproduction?

...

These results call for some fundamental re-thinking of what aging is: [that] aging is not inevitably a cumulative and unremitting process of deterioration. Instead, aging might be best conceived as a facet of [evolutionary] adaptation ... under sufficiently benign environmental conditions, individuals from species as disparate as humans and fruit flies can survive a protracted aging period and reach a subsequent late-life respite in which fitness-component deterioration stops, a phase permitted by the complete attenuation of the forces of natural selection relative to the effects of genetic drift.

The details of the way in which these researchers put forward their hypothesis to reconcile the late-life plateau in aging with existing ideas on the evolution of aging is not conceptually straightforward or easy to understand - but is interesting. As they put it:

This vision of what underlies aging may be off-putting for some, given its theoretical complexities and difficulties for experimental design. No doubt many physicists felt the same way about the destruction of the elegant late nineteenth Century version of Newtonian mechanics by the advent of relativistic and quantum mechanics, in the period from 1905 to 1945. But paradigm transitions in science are generally like that, requiring that we abandon comfortable theories in favor of those that are significantly less wrong.

It remains to be seen whether this view of aging merits comparison with the signature physics of the 20th century, but it is certainly true that a lot of new theorizing on evolution and aging is taking place these days - no doubt driven by an increasing interest in the biology of aging and the prospects of new medicine to intervene in the aging process.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

There are many possible forms of therapy that either might be built or are presently being built atop of a greater knowledge of stem cells and cell biotechnologies. Cultured populations of stem cells can be let loose into the body to do their work, or existing cells can be directed to take action where they would normally stand aside, or tissues can be constructed for transplant, and many more variants upon these themes. As explained in a recent open access paper, stem cells can also stand duty as a method of delivering a therapy rather than being a form of therapy themselves: they can move around the body largely unhindered, and different types of stem cells have quite strong opinions as to which part of the body they would like to migrate towards. Given the right signals, stem cells can even be directed to quite specific locations - consider the way in which cells respond to injury, for example. This is but one of countless signals that cause stem cells to travel or take specific actions: a great deal of future medicine will be based on better understanding and control over stem cells in the body.

So let us say that you want to move a dose of a fragile therapeutic molecule into the brain, past the blood-brain barrier - and, further, to quite specific locations within the brain. Why not enlist stem cells to carry it in? Unfortunately it's not completely straightforward - stem cells have their own ideas as to where they would like to go, and if that isn't suited to the need at hand, then further improvement in control is needed. The basic concept still looks promising, however, even though early attempts are not achieving great results:

Transplantation of neural stems cells (NSCs) could be a useful means to deliver biologic therapeutics for late-stage Alzheimer's disease (AD). In this study, we conducted a small preclinical investigation of whether NSCs could be modified to express metalloproteinase 9 (MMP9), a secreted protease reported to degrade aggregated A? peptides that are the major constituents of the senile plaques.

Our findings illuminated three issues with using NSCs as delivery vehicles for this particular application. First, transplanted NSCs generally failed to migrate to amyloid plaques, instead tending to colonize white matter tracts. Second, the final destination of these cells was highly influenced by how they were delivered.

...

Overall, we observed long-term survival of NSCs in the brains of mice with high amyloid burden. Therefore, we conclude that such cells may have potential in therapeutic applications in AD but improved targeting of these cells to disease-specific lesions may be required to enhance efficacy.

The medicine of the 2040s may involve more cell therapies than any other area at the present pace: cells ordered around, changed in situ into augmented bioartifical machinery to conduct repairs or deliver compounds to needed locations, or even joined by artificial cells that carry out similar duties but more effectively. We are built of cells, so it makes some sense that our medical technology might eventually also be largely built of cells, act through cells, or otherwise be based on the direct control and repair of cells.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Posted by Harriet Hall on January 20, 2009

Much nonsense has been written in the guise of longevity medicine. In Fantastic Voyage, Ray Kurzweil explains why he takes 250 pills every day and spends one day a week at a clinic getting IV vitamins, chelation, and acupuncture. He is convinced this regimen will keep him alive long enough for science to figure out how to keep him alive forever. In Healthy Aging, Andrew Weil chips in with his own mixture of science and magic. I pointed out the flaws in their reasoning in a review for Skeptic magazine available online. There are many other popular books that promise to tell you how to live longer. Most of them amount to little more than speculation based on extrapolations from animal studies, in vitro studies, and odd non-clinical facts.

There simply is no evidence that any intervention will extend the human life span. The most promising idea from animal studies, severe calorie restriction, is not practical or palatable and would make adequate nutrition difficult. We dont know how to prolong human life to, say, 130 years; but we do know how to prevent a number of diseases from causing premature demise at 60 or 70. Thats what real longevity medicine means.

To counteract all the belief-based and speculation-based longevity medicine, we needed a science-based longevity book. And now we have it. Carl Bartecchi, MD and Robert W. Schrier, MD have written a book entitled Living Healthier and Longer What Works, What Doesnt. The price is right it is available online for free download.

This book is based firmly on science. It covers major diseases, risk factors, and the interventions that have been tested and shown to improve outcome. It doesnt promise survival beyond the expected life span, but it shows you how to minimize the risk of avoidable diseases and live as long as possible given the constraints of genetic inheritance and the accidents of chance.

For those who think modern medicine doesnt focus on prevention, heres a whole book of refutation. It stresses appropriate screening tests, immunizations, smoking cessation, weight control, healthy diet, exercise, and proven interventions like low-dose aspirin. It even includes guidelines for the responsibilities of doctors and the responsibilities of patients so they can work together optimally.

I have a few quibbles with details: they recommend breast self-exam, which has recently been shown not to improve survival from breast cancer, and they recommend limiting egg consumption because of the cholesterol in eggs, outdated advice that most science-based doctors would disagree with based on more recent evidence. But most of what they say is solid mainstream science backed up by good quality evidence.

They cover vitamins in detail. They discuss the failures of antioxidants in clinical studies and the recent changes in recommendations for vitamin D. They dispel many popular myths:

Studies do not show that a healthy person who takes extra nutrients has increased energy, reduced fatigue, or added disease protection. .

The title of one chapter is particularly refreshing:

Read more here:
Science-based Longevity Medicine Science-Based Medicine

From the Sydney Morning Herald: "A full thickness artificial skin which should dramatically reduce the pain and scarring associated with skin grafts is being developed by Sydney researchers. Burns experts from the University of Sydney and Concord Hospital have started animal trials of a living skin that is grown outside the body and is completely functional when grafted on to the body. Unlike traditional skin grafts, which involve only the thin outer layer of the skin known as the epidermis, the new skin will be able to replace the crucial second layer of skin called the dermis. ... It takes the body weeks to grow into a skin graft and in that time a lot of excess elastic fibres and collagen will be produced that will then turn into a scar. The scar contracts and it can get so tight that patients lose the movement of their mouth and can't talk, or they can't bend their fingers. ... Initial testing of the artificial dermis in mice has found it does not scar and contract when it is transplanted. ... The research has been so successful that a new foundation has been created to centralise the burns research being done at three Sydney hospitals. ... They hope to create scaffolds that can individualise the skin, allowing it to be different colours."

View the Article Under Discussion: http://www.smh.com.au/lifestyle/wellbeing/fully-functional-artificial-skin-being-trialled-by-sydney-researchers-20100614-yaau.html

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

This seems like an interesting marker of public awareness of aging science; one of the noted researchers in the field recently started on a biweekly column for a local paper. Links to the columns published to date can be found on this page: "In my last column I discussed something we all know intuitively: Generally speaking, larger species of animals live longer than smaller species and this pattern extends even to whales that live more than 200 years. Are there dramatic exceptions to this rule - like people, for instance? Think of other mammals about our size, such as deer or mountain lions or seals. Don't we live longer than they do? The answer is, 'Yes, we do.' Humans live about five times as long as the average mammal of the same size, which makes us pretty special - but not as special as bats. Texas is bat country, as anyone who has watched millions of bats boil out of Bracken Cave or from under Austin's Congress Avenue Bridge can verify. What many people don't realize is how long bats live. For their size, bats are the longest-lived mammals by far, living up to 10 times as long as an average mammal of similar size. ... Think about this for a second. Your dog or cat, eating the best food science can provide, protected from predators and the elements and vaccinated against all sorts of diseases, is doing well to reach 15 to 20 years of age. By comparison, in order for a bat in the wild to survive it must catch its own prey, elude predators, resist climatic extremes, and avoid a wide range of infectious diseases. Yet despite these challenges, bats can live twice as long as your pampered pet." Current thinking on bat longevity looks to be similar to theories on naked mole rat longevity - it has to do with resistance of cell membranes (and especially mitochondria) to oxidative damage, otherwise known as the membrane pacemaker hypothesis of aging. This is thought to have developed in bats, and in birds, in respond to the metabolic demands of flight.

Link: http://barshop.uthscsa.edu/main/newsseminars/news/u50

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I've noted work on correlations between air pollution and reduced life expectancy in past years; the statistical differences are usually very small in comparison to what you can do for yourself via calorie restriction and exercise, as air pollution in wealthier regions of the world is a fraction of what it was a century past. As populations became radically richer in the course of the past three centuries, the luxury of being able to pay for a better environment became possible - either directly or through investment in technologies that cause less pollution in the course of achieving their end goals. It wasn't all that long ago, for example, that there were dead rivers in the US and Western Europe. Those rivers would still be dead if not for the fact that our societies are far wealthier than those of our grandparents; to be able to be an environmentalist is very much a luxury. It requires sufficient surrounding wealth or knowledge to be able to do things a different way.

In any case, here is a recent study on air quality and life expectancy in China - a region of the world that is still largely an expanse of 20th-century styled comparative poverty, scattered with enclaves and belts of modern wealth.

Air Pollution Shortens Life Expectancy and Health Expectancy for Older Adults: The Case of China.

Outdoor air pollution is one of the most worrying environmental threats China faces today. Comprehensive and quantitative analyses of the health consequences of air pollution in China are lacking. This study reports age- and sex-specific life expectancy and health expectancies (HEs) corresponding to different levels of air pollution based on associations between air pollution and individual risks for a host of health conditions and mortality net of individual- and community-level confounders.

...

The main outcome measures in this study include life expectancy estimated from mortality and HEs based on five health conditions including activity of daily living, instrumental activity of daily living, cognitive status, self-rated health, and chronic conditions. Net of the controls, exposure to outdoor air pollution corresponded to subsequent reductions of life expectancy and HEs for all five health conditions. These detrimental pollution effects were stronger for women. The gap in life expectancy between areas with good air quality and moderately heavily polluted areas was 3.78 years for women of age 65 and 0.93 years for men. The differences in HEs at age 65 were also large, ranging from 1.47 years for HE for good self-rated health in men to 5.20 years for activity of daily living disability-free HE in women.

Air quality tends to be mixed up with a range of other confounding factors, however. This requires careful work on the part of researchers to have a chance of teasing out air quality effects independently of other factors that lead people to remain in areas of poor air quality:

I would be willing to wager that the correlation has more to do with the relative wealth of these areas and those who make the economic choice to live there, as well as access to medical technology and lifestyle choices. Things are rarely as simple as a two-parameter study casts them to be.

Still, aging is damage, and there's do great doubt that very polluted air does damage people over the long term, to a degree related to the level of pollution: inflammation, increased risk of age-related disease, outright lung damage, risk of cancer, that sort of thing. But once the air becomes clean enough for effects to be subtle - meaning much less in magnitude that effects of exercise, differences in wealth, intelligence, or even state of mind - then attention should turn to other controllable factors in life.

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The latest issue of the open access journal Immunity & Aging includes a number of interesting papers covering the overlap between genetic contributions to natural variations in longevity and the aging of the immune system - which contributes to a range of age-related dysfunction and systems failure. They are very much in the mainstream model of narrow, unambitious, cautious vision: aiming for and expecting only modest, gradual improvements in health and longevity. Even in this time of radical change in biotechnology, the old habits of incrementalism and understatement regarding the bounds of the possible for human longevity are only slowly fading. The future must be one of ambitious, grand visions in medical science and funding for research if we are to benefit fully from the true potential of biotechnology. In any case, these papers remain interesting for what they are, and are available as provisional PDFs at this time - the download links are on the abstract pages below.

"Positive biology": the centenarian lesson:

The extraordinary increase of the elderly in developed countries underscore the importance of studies on ageing and longevity and the need for the prompt spread of knowledge about ageing in order to satisfactorily decrease the medical, economic and social problems associated to advancing years, because of the increased number of individuals not autonomous and affected by invalidating pathologies. Centenarians are equipped to reach the extreme limits of human life span and, most importantly, to show relatively good health, being able to perform their routine daily life and to escape fatal age-related diseases. Thus, they are the best example of extreme longevity, representing selected people in which the appearance of major age-related diseases, such as cancer, and cardiovascular diseases among others, has been consistently delayed or escaped. ... The aim is to realize, through a "positive biology" approach (rather than making diseases the central focus of research, "positive biology" seeks to understand the causes of positive phenotypes, trying to explain the biological mechanisms of health and well-being) how to prevent and/or reduce elderly frailty and disability.

Epidemiological, genetic and epigenetic aspects of the research on healthy ageing and longevity:

In this article we aimed to overview the research on the biological basis of human healthy ageing and longevity, discussing the role of epidemiological, genetic and epigenetic factors in the variation of quality of ageing and lifespan, including the most promising candidate genes investigated so far. Moreover, we reported the methodologies applied for their identification, discussing advantages and disadvantages of the different approaches and possible solutions that can be taken to overcome them.

Genetics of longevity. Data from the studies on Sicilian centenarians:

Scientists have focused their attention on centenarians as optimal model to address the biological mechanisms of "successful and unsuccessful ageing". They are equipped to reach the extreme limits of human life span and, most importantly, to show relatively good health, being able to perform their routine daily life and to escape fatal age-related diseases, such as cardiovascular diseases and cancer. Thus, particular attention has been centered on their genetic background and immune system. In this review, we report our data gathered for over 10 years in Sicilian centenarians. Based on results obtained, we suggest longevity as the result of an optimal performance of immune system and an over-expression of anti-inflammatory sequence variants of immune/inflammatory genes.

Extending healthy ageing: nutrient sensitive pathway and centenarian population:

To increase our understanding of how ageing works, it may be advantageous to analyze the phenotype of centenarians, perhaps one of the best examples of successful ageing. Healthy ageing involves the interaction between genes, the environment, and lifestyle factors, particularly diet. Besides evaluating specific gene-environment interactions in relation to exceptional longevity, it is important to focus attention on modifiable lifestyle factors such as diet and nutrition to achieve extension of health span. Furthermore, a better understanding of human longevity may assist in the design of strategies to extend the duration of optimal human health.

The application of genetics approaches to the study of exceptional longevity in humans: potential and limitations:

The average life-span of the population of industrialized countries has improved enormously over the last decades. Despite evidence pointing to the role of food intake in modulating life-span, exceptional longevity is still considered primarily an inheritable trait, as pointed out by the description of families with centenarian clusters and by the elevated relative probability of siblings of centenarians to become centenarians themselves. However, rather than being two separate concepts, the genetic origin of exceptional longevity and the more recently observed environment-driven increase in the average age of the population could possibly be explained by the same genetic variants and environmentally modulated mechanisms (caloric restriction, specific nutrients). In support of this hypothesis, polymorphisms selected for in the centenarian population as a consequence of demographic pressure have been found to modulate cellular signals controlled also by caloric restriction.

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Damage to mitochondrial DNA contributes to aging, and mitochondrial function is in general influential upon aging - damage causes harm by preventing the production of protein machinery vital to mitochondrial activity, which is the start of a long process that sees cells overtaken by dysfunctional mitochondria, and exporting their dysfunction to surrounding tissue by emitting harmful reactive molecules. There are numerous different sorts of DNA damage, however. Point mutations, for example, have been shown to do little to aging. Deletions, where whole reaches of DNA are knocked out, are a different story, and here researchers are investigating how this form of DNA damage varies between species: "Deletion mutations within mitochondrial DNA (mtDNA) have been implicated in degenerative and aging related conditions, such as sarcopenia and neuro-degeneration. While the precise molecular mechanism of deletion formation in mtDNA is still not completely understood, genome motifs such as direct repeat (DR) and stem-loop (SL) have been observed in the neighborhood of deletion breakpoints and thus have been postulated to take part in mutagenesis. In this study, we have analyzed the mitochondrial genomes from four different mammals: human, rhesus monkey, mouse and rat ... Our analysis revealed that in the four species, DR and SL structures are abundant and that their distributions in mtDNA are not statistically different from randomized sequences. However, the average distance between the reported age associated mtDNA breakpoints and their respective nearest DR motifs is significantly shorter than what is expected of random chance in human and rhesus monkey, but not in mouse and rat, indicating the existence of species specific difference in the relationship between DR motifs and deletion breakpoints. In addition, the frequencies of large DRs tend to decrease with increasing lifespan among the four mammals studied here, further suggesting an evolutionary selection against stable mtDNA misalignments associated with long DRs in long-living animals."

Link: http://dx.doi.org/10.1371/journal.pone.0035271

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An open access review paper looks at how the study of fly aging has informed the life sciences: "it is likely that not all senescent physiological changes revealed in flies can be simply translated to humans. However, flies and humans often show very similar age-related physiological phenotypes suggesting that at least some of the basic biological properties and mechanisms that regulate longevity are conserved amongst species. ... It is well-known that advances in medicine and health care have significantly contributed to increased longevity in humans over the last 100 years. There is also a clear trend toward increased life expectancy including an increase in the numbers of people living to an advanced age and the number of people with chronic age-related diseases. These trends emphasize the need to understand the genetic and physiological factors underlying biological aging and particularly, those that promote healthy aging. ... there are three ways to extend lifespan: increasing early survival rate, increasing late survival rate, or delaying senescence. Remarkably, the first two do not affect basic aging processes. For example, the first one leads to a significant increase in mean but not maximum lifespan, while the second one leads to change in a maximum but not mean lifespan. Delayed senescence, in turn, leads to a significant increase in both the mean and maximum lifespan. ... This raises the question as to whether healthspan and delayed senescence are inter related. As stated above, while many genes have been shown to extend lifespan, these may have little or no ability to delay physiological senescence. In other words, the period of functional disability before death may increase despite the fact that the total duration of life is increased. Thus, the search for appropriate biomarkers applicable to monitor functional senescence is highly important with regards to healthy aging and age-related diseases." These cautions are very much focused on the mainstream research goals of slowing the rate of aging through genetic and metabolic alterations; they have little relevance to efforts aimed at producing continuous repair of aging.

Link: http://www.frontiersin.org/Integrative_Physiology/10.3389/fphys.2012.00106/full

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Via ScienceDaily: researchers "have identified a group of 'aging' genes that are switched on and off by natural mechanisms called epigenetic factors, influencing the rate of healthy aging and potential longevity. The study also suggests these epigenetic processes - that can be caused by external factors such as diet, lifestyle and environment - are likely to be initiated from an early age and continue through a person's life. The researchers say that the epigenetic changes they have identified could be used as potential 'markers' of biological aging and in the future could be possible targets for anti-aging therapies. ... the study looked at 172 twins aged 32 to 80 from the TwinsUK cohort. The researchers looked for epigenetic changes in the twins' DNA, and performed epigenome-wide association scans to analyze these changes in relation to chronological age. They identified 490 age related epigenetic changes. They also analysed DNA modifications in age related traits and found that epigenetic changes in four genes relate to cholesterol, lung function and maternal longevity. To try to identify when these epigenetic changes may be triggered, the researchers replicated the study in 44 younger twins, aged 22 to 61, and found that many of the 490 age related epigenetic changes were also present in this younger group. The researchers say these results suggest that while many age related epigenetic changes happen naturally with age throughout a person's life, a proportion of these changes may be initiated early in life."

Link: http://www.sciencedaily.com/releases/2012/04/120419191709.htm

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