Fight Aging!

FIGHT AGING! NEWSLETTER
December 2nd 2013

The Fight Aging! Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to Fight Aging!

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CONTENTS

• When Will the $100 Million Donations Start to Arrive for Rejuvenation Research?
• Jason Hope on Philanthropy
• Promising Results from Cancer Immune Therapy Trials
• Recently Published Research on Exercise and Aging
• "Are They Selling a Product?" as a Test For Longevity Science
• Latest Headlines from Fight Aging!
  • Proposing to Print a New Heart Within a Decade
  • A Perspective on Coming to Support Longevity Science
  • Growing Artificial Skin From Umbilical Cord Cells
  • Cellular Senescence in Aging as Adapted Tool of Development
  • Regular Exercise Correlates With Better Long Term Health
  • A Review of Natural Mechanisms for Removing Tau
  • Ray Kurzweil and Radical Life Extension
  • Multiple Methods of Regeneration in Similar Salamander Species
  • Correlations With Species Longevity Found in the Lipidome
  • A Look at Lipid Replacement Therapy

WHEN WILL THE $100 MILLION DONATIONS START TO ARRIVE FOR REJUVENATION RESEARCH?
https://www.fightaging.org/archives/2013/11/when-will-the-100-million-donations-start-to-arrive-for-rejuvenation-research.php

Wealth does not grant vision, and arguably the process of becoming extraordinarily wealthy requires a person who does not devote a great deal of interest and effort to anything beyond running that process. Usually this involves a great deal of work, a great deal of learning, a great deal of personal growth. But if you happen to also be someone who wants to change the world in ways that require a great deal of money - such as through medical research, for example - then you probably won't get much past the level of multi-millionaire. You'll choose to start investing in doing good rather than doubling down on the money-making road.

I think that this goes some way towards explaining the conservatism and lack of vision that accompanies $100 million and larger donations to charitable causes: philanthropic structural investments we might term them. Putting that much money towards a goal requires a significant project just to understand how to best spend it, even when the aim is very clear, such as "let us cure this one disease." It is very, very rare to see this much money arrive in support of a young cause, as the people with that much money to invest have not led the lives that would lead them to understand the cutting edge of any of the fields they might support. This is really just specialization at work.

What has to happen to make it likely that someone exceedingly wealthy will donate $100 million to furthering a field of research? There must have been decades of growth, including the very earliest research interest; then a surge in the scientific output; then hundreds of millions of dollars of funding; a business cycle of new companies; a brace of failures; thousands of articles in the popular press; a backlash and down cycle; resurgence and renewed investment in the billions of dollars; tremendous progress; excitement in the public and scientific communities; tens of thousands of researchers flocking to the field; a new breakthrough every week; ten years of incremental advances demonstrated in commercial medicine; early therapies demonstrated in the field; the branch of medicine now known to every common fellow on the street.

That is what has to happen for the average exceedingly wealthy philanthropist to feel comfortable devoting time, effort, and large sums of money into making a structural investment in a field of medicine. Think of the history and presently enthusiastic, well-funded, widely supported state of stem cell research while you take a look at this article:

Sanford donates $100 million to UCSD

Philanthropist Denny Sanford is donating $100 million to UC San Diego to speed up attempts to turn discoveries about human stem cells into drugs and therapies to treat everything from cancer and Alzheimer's disease to spinal-cord injuries and weak hearts. The $100 million donation represents the core of a larger $275 million effort by UC San Diego to create some of the first clinical trials based on human stem cells, which can develop into many different types of cells, including some that can help repair tissues and organs. The newly created Sanford Stem Cell Clinical Center will enable the school to hire 20 to 25 scientists and recruit patients for drug trials.

One of the points raised by Peter Thiel and others is that this sort of support of well-established research fields is where philanthropy is at its least useful. I don't want to point to the example above to say "do better," because I don't think I have the standing to do so. Sanford has arguably done more to make the world a better place with that work than I ever will. But still: at some point the philanthropic community should figure out a way to be something other than last to the party, adding to a sure thing at the end of the day rather than boldly taking risks in the early days to more rapidly build the medical technologies needed for a better world.

I would like the near future of rejuvenation biotechnology to be something other than a twenty to thirty year climb to get to the point at which big philanthropy and the world at large notices its existence and decides that it is a legitimate field of research, worthy of additional support. To arrive at that position, billions will have been raised and spent, early therapies deployed, and thousands of scientists engaged. But it would all go so very much faster if someone would just decide tomorrow that the best thing to do was to make a $100 million investment in building the vision for rejuvenation biotechnology laid out by the SENS Research Foundation.

I know this with confidence because I've personally spent enough time over the past decade to understand the research landscape and the prospects for new and radically disruptive advances in medical biotechnology relating to aging and longevity. As a general rule, anyone with $100 million to invest has not. Such is the human condition.

JASON HOPE ON PHILANTHROPY
https://www.fightaging.org/archives/2013/11/jason-hope-on-philanthropy.php

Jason Hope, you might recall, has provided half a million dollars in research funding to the SENS Research Foundation, used to establish a SENS laboratory at Cambridge in order to push forward with the Foundation's AGE-breaker program. AGE-breakers are drugs or other treatments capable of breaking down advanced glycation end-products (AGEs). These are a class of metabolic waste product that accumulate in our tissues to cause significant harm that includes the progressive loss of elasticity in skin and blood vessels.

There is, on the whole, far too little work undertaken today on AGE-breaker treatments in comparison to the benefits that a treatment could bring. What little research has taken place over the past twenty years unfortunately produced no effective therapies. As it turned out the AGEs that are important in short-lived laboratory animals are not the same at all as those that are important in humans - something that would have been challenging to identify until comparatively recently, and which resulted in promising animal studies that then went nowhere in commercial trials.

Now, however, researchers know that the vast majority of all AGEs in human tissues consist of just one type, called glucosepane - so the way is open for bold philanthropists and forward-looking researchers to build therapies that will be effective in removing this contribution to degenerative aging. Glucospane removal is one of the areas in which the SENS Research Foundation and its backers pick up the slack, undertaking important rejuvenation research that is neglected by the mainstream, even though it was exactly the mainstream research community that produced all of the studies and evidence that demonstrate the important role of glucospane in aging.

In any case, I should point out that Jason Hope runs a website and blog in which he discusses his take on philanthropy and his support for research aimed at extending healthy human life and rejuvenating the old. This makes for an interesting follow-on from yesterday's post on big philanthropy. More folk of this ilk would certainly be a good thing, and I'm always pleased to see more of the better connected people in this world of ours speaking openly of their support for rejuvenation biotechnology.

Philanthropy

Philanthropy has become a big focus for me. The organizations I have chosen to stand behind have come from many facets of my life. One of my passions has become the research done at the SENS Research Foundation. Their involvement in anti aging is not just about wanting to live forever. It's about creating a longer, better quality of life.

Foundations like SENS are taking a different approach to anti-aging. They are focused on finding cures for disease that break down the body and thus cause us to age faster than we should. Disease like Alzheimer's and heart and lung disease affect all functions of the body. Traditional medicine looks at treating these diseases after they happen. We want to focus on stopping these diseases from ever happening. We have spent so much time focused on medication for treating disease and not enough time on preventing that disease from ever happening.

By supporting scientific research that thrives through innovation and is not afraid to challenge the modern school of thought we will continue to break down walls.

A 21st Century Philanthropic Model For Philanthropy

Can you conceive of a world without age-related disease, disability and suffering? What about a world in which it's possible for the average person to live 120 healthy years? While it may sound like a utopian dream, such a world is the exact goal of some of society's most brilliant scientists and visionary leaders. At this very minute, groundbreaking work is underway at universities across the globe as researchers attempt to apply regenerative medicine to age-related disease through the repair of damage to tissue, cells and molecules within the body. While this research couldn't be possible without the leadership of the world's wealthiest philanthropists, it also relies upon the collective power of everyday people who have joined forces in their commitment to a better quality of life for all.

Traditionally, big ticket donors have been the primary target for fundraising programs. Research has consistently shown that the bulk of donor funds come from a small percentage of the wealthiest donors: in fact, a full 75 percent of funds raised come from gifts of over $1 million.

Instead of resigning themselves solely to the influence of the individual, non-profits are turning to the collective power of a group. The MFoundation's "The 300 Pledge" fundraising campaign is an exciting example of this method in practice. The 300 Pledge asks 300 funders to commit $1,000 a year for 25 years toward critical research aimed at ending age-related diseases. When broken down, this goal is manageable for many households: just $3 a day or $85 a month - less than your daily tab at Starbucks. Obviously, the model is working: to date, 291 people have taken up the challenge, with nine spots remaining.

As evidenced by the magnificent philanthropy of people like Peter Thiel, Bill Gates and others like them, it's obvious that one person can make a difference. However, fundraising challenges, like MFoundation's "The 300," also demonstrate the power of a dedicated group of people to foster real world change for the billions of people living in the world today as well as the generations that follow. In doing so, those who take up the challenge create a unique and world-altering legacy for themselves.

PROMISING RESULTS FROM CANCER IMMUNE THERAPY TRIALS
https://www.fightaging.org/archives/2013/11/promising-results-from-cancer-immune-therapy-trials.php

The future of cancer treatment is targeting: deploying therapies that seek out and destroy cancer cells while leaving other cells unharmed, resulting in few or no side-effects. Many different approaches to achieving this end presently under research and development, and the most advanced have been in clinical trials for a few years now. Using the immune system as a starting point is one of the more promising strategies. After all, why build a whole new set of cell-targeting and cell-killing machinery when you can adapt the sophisticated, adaptive set that already exists?

Even considering only the use of immune cells as therapeutic agents there is still a very broad range of approaches that can be used to produce targeted therapies, and many varieties of potential therapy are presently either under development or in trials. This is a very active field of research, and on the whole things are looking very promising for everyone who is at least a couple of decades away from the stage of life in which developing cancer is likely. The coming generations of new therapies will be highly effective and much less debilitating. When coupled with vastly improved detection and screening technologies, the end result will be that cancer will recede from its present position as one of the principal causes of age-related mortality.

We still need rejuvenation therapies to deal with the underlying causes of degenerative aging, but given the present pace of progress, I don't feel that cancer is something to be greatly concerned about - or at least not in comparison to the other underlying aspects of aging, where there is far less ongoing work and enthusiasm for progress. Here are two recent examples of cancer immune therapies presently in the clinical trial stage of development, both of which show considerable promise:

Cancer meets its nemesis in reprogrammed blood cells

"THE results are holding up very nicely." Cancer researcher Michel Sadelain is admirably understated about the success of a treatment developed in his lab at the Memorial Sloan-Kettering Cancer Center in New York. In March, he announced that five people with a type of blood cancer called acute lymphoblastic leukaemia (ALL) were in remission following treatment with genetically engineered immune cells from their own blood. One person's tumours disappeared in just eight days. [A] further 11 people have been treated, almost all of them with the same outcome. Several trials for other cancers are also showing promise.

T-cells normally travel around the body clearing sickly or infected cells. Cancer cells can sometimes escape their attention by activating receptors on their surface that tell T-cells not to attack. ALL affects another type of immune cell, the B-cells, so Sadelain takes T-cells from people with ALL and modifies them to recognise CD19, a surface protein on all B-cells - whether cancerous or healthy. After being injected back into the patient, the reprogrammed T-cells destroy all B-cells in the person's body. This means they need bone marrow transplants afterwards to rebuild their immune systems. But because ALL affects only B-cells, the therapy guarantees that all the cancerous cells are destroyed.

Update: 50 Percent of Patients in Cedars-Sinai Brain Cancer Study Alive After Five Years

Eight of 16 patients participating in a study of an experimental immune system therapy directed against the most aggressive malignant brain tumors - glioblastoma multiforme - survived longer than five years after diagnosis. Seven of the 16 participants still are living, with length of survival ranging from 60.7 to 82.7 months after diagnosis. Six of the patients also were "progression free" for more than five years, meaning the tumors did not return or require more treatment during that time. Four participants still remain free of disease with good quality of life at lengths ranging from 65.1 to 82.7 months following diagnosis.

Results published in January at the end of the study showed median overall survival of 38.4 months. Typically, when tumor-removal surgery is followed by standard care, which includes radiation and chemotherapy, median length of survival is about 15 months. Median progression-free survival - the time from treatment to tumor recurrence - was 16.9 months at study's end. With standard care, the median is about seven months.

Even the most dangerous and challenging cancers are starting to yield in the face of more targeted approaches, and the pace of progress in the laboratory is speeding up. We can look forward to cancer as a controlled, cured condition, no worse a threat for anyone with access to modern medicine than smallpox or tuberculosis.

RECENTLY PUBLISHED RESEARCH ON EXERCISE AND AGING
https://www.fightaging.org/archives/2013/11/recently-published-research-on-exercise-and-aging.php

The human research that compellingly demonstrates that regular moderate exercise is very good for long term health is overwhelmingly epidemiological in nature. Researchers establish survey populations and mine existing data to find associations between health, aging, and exercise. The challenge here is always the identification of correlation versus causation: does exercise cause better health or does better health lead to more exercise? In many studies that has to be left an open question by the nature of the data and the study protocol - but some provide fairly compelling interpretations of causation.

Animal studies on the other hand leave absolutely no room for doubt on the question of exercise as a means to increase healthspan (if not maximum life span), improving long term health, slowing progression of measures of aging, and reducing incidence of age-related disease. It has been shown over and again in rigorous studies that exercise produces considerable improvements in health. The results, and the size of corresponding correlated health differences in human studies, are far better than can be achieved by any medical technology presently available in clinics.

For some researchers the data on exercise are a matter of backing up simple health advice: get out there and exercise in order to be healthier and extend your healthy life expectancy. But for others, this and investigations of the molecular biology of exercise form the ground floor for future development of exercise mimetic drugs. In an analogous way to ongoing work on calorie restriction mimetics, researchers will find ways to trigger some of the mechanisms of exercise to produce benefits without the exertion.

These research programs are producing and will continue to produce a wealth of data on how metabolism, aging, and lifestyle choices interact. But given that the benefits to health are already fully available the old-fashioned way, one has to think that perhaps all of this effort might be better directed towards research programs more likely to produce rejuvenation of the elderly - something that exercise and calorie restriction cannot achieve.

Road to exercise mimetics: targeting nuclear receptors in skeletal muscle

Skeletal muscle is the largest organ in the human body and is the major site for energy expenditure. It exhibits remarkable plasticity in response to physiological stimuli such as exercise. Physical exercise remodels skeletal muscle and enhances its capability to burn calories, which has been shown to be beneficial for many clinical conditions including the metabolic syndrome and cancer.

Nuclear receptors (NRs) comprise a class of transcription factors found only in metazoans that regulate major biological processes such as reproduction, development, and metabolism. Recent studies have demonstrated crucial roles for NRs and their co-regulators in the regulation of skeletal muscle energy metabolism and exercise-induced muscle remodeling. While nothing can fully replace exercise, development of exercise mimetics that enhance or even substitute for the beneficial effects of physical exercise would be of great benefit. The unique property of NRs that allows modulation by endogenous or synthetic ligands makes them bona fide therapeutic targets.

Exercise Training Initiated in Late Middle Age Attenuates Cardiac Fibrosis and Advanced Glycation End-product Accumulation in Senescent Rats

While it has long been postulated that exercise training attenuates the age-related decline in heart function normally associated with increased fibrosis and collagen cross-linking, the potential benefits associated with exercise training initiated later in life are currently unclear. To address this question, [rats] underwent treadmill-based exercise training starting in late middle age and continued into senescence (35 months) and were compared with age-matched sedentary rats.

Hearts were examined for fibrosis and advanced glycation end-products in the subendocardial layer of left ventricular cross-sections. Exercise training of late middle-aged rats attenuated fibrosis and collagen cross-linking, while also reducing age-related mortality between late middle age and senescence. This training was also associated with an attenuated advanced glycation end-product (AGE) accumulation with aging, suggesting a decrease in collagen cross-linking.

"ARE THEY SELLING A PRODUCT?" AS A TEST FOR LONGEVITY SCIENCE
https://www.fightaging.org/archives/2013/11/are-they-selling-a-product-as-a-test-for-longevity-science.php

A recent article on the Longevity Dividend initiative included these comments from some of the backers:

One fountain of youth; hold the snake oil

"We now know that aging is modifiable in the laboratory," said Dan Perry, president of the Alliance for Aging Research. "When you do this, you also eradicate or greatly postpone the whole array of diseases that come with aging."

I know what you're thinking: You've heard all this before. We are constantly, shamelessly bombarded by profit-seekers - and yes, the complicit media - who promise an easy way out of aging, from gingko biloba to red wine to hormone or stem cell replacement therapy. So how, I asked the distinguished scientists in New Orleans, do they plan to distinguish the Longevity Dividend from all those empty promises of the past and present?

"It's a greater threat than we may sometimes realize," Perry acknowledged. "Eons of snake oil salesmen have tarnished the genuine science that's starting to emerge. Just one example is human growth hormone, and the entire industry that came up around it."

S. Jay Olshansky said every genuine anti-aging breakthrough is being seized on by hucksters and sold to a gullible public. But, he added, there's an easy way for you to tell good medicine from bad. "Part of the problem," he said, "is that when research scientists have published papers in recent decades, as soon as a glimmer appears they start selling it to the public for profit, before there are studies for safety and efficacy.

"But we are not selling anything to the public. If they are selling it now, it doesn't exist."

This is a good general rule of thumb when it comes to the intersection of health, aging, and longevity. It won't be a good rule for much longer, because the cutting edge of medical research and development is not so many years away from turning out actual first attempts at rejuvenation therapies, or ways to adjust metabolism to modestly slow aging, but it is a good rule for today and for the next few years at least.

Why? Because despite the many ways of extending life in laboratory animals there is as yet no commercially available technology that can be shown to produce more than a fraction of the health and longevity benefits of regular exercise and calorie restriction. All of the most advanced lines of research than might produce more effective ways to extend life in healthy individuals, such as some of those described in the SENS proposals, are at least five to ten years removed from early clinical access even in the best case scenarios for funding and aggressive medical tourism.

So if someone is trying to sell you a product today, with the promise that it will greatly extend your life, then that person is a huckster. Plain and simple. The best and only sensible use for your money for the foreseeable future is to provide support for the advocacy and medical research programs that will speed the advent of future rejuvenation biotechnologies, therapies that will actually extend life and restore youthful function to a meaningful degree once realized.

LATEST HEADLINES FROM FIGHT AGING!

PROPOSING TO PRINT A NEW HEART WITHIN A DECADE
Monday, November 25, 2013
https://www.fightaging.org/archives/2013/11/proposing-to-print-a-new-heart-within-a-decade.php

Researchers are becoming more comfortable putting forward timelines for organ printing, which we might take as a sign of progress in and of itself:

A team of cardiovascular scientists has announced it will be able to 3D print a whole heart from the recipients' own cells within a decade. "Funding is very limited as this is a new area. But as bioprinting successes occur the interest will increase and then funding - so many breakthroughs have occurred in this way with a new untested idea that is moved forward with limited resources. For bioprinting it is the end of the beginning as bioprinted structures are now under intense study by biologists."

Stuart K Williams is heading up the hugely ambitious project as executive and scientific director of the Cardiovascular Innovation Institute. Williams says he and his team of more than 20 have already bioengineered a coronary artery and printed the smallest blood vessels in the heart used in microcirculation. "These studies have reached the advanced preclinical stage showing printed blood vessels will reconnect with the recipient tissue creating new blood flow in the printed tissue."

The team has also worked on other methods of bioengineering tissue, including electrospinning for the creation of large blood vessel scaffolds that can then be joined with bioprinted microvessels. The Cardiovascular Innovation Institute is now developing bespoke 3D printers for the job with a team of engineers and vascular biologists. Though for now those printers are focusing on replicating the parts, the plan is to print the whole in one go in just three hours, with a further week needed for it to mature outside of the body. Certain parts will need to be printed and assembled beforehand, including the valves and the biggest blood vessels. "Final construction will then be achieved by bioprinting and strategic placement of the valves and big vessels," says Williams, who asserts that they are "on schedule" to build the bioficial heart within the decade marker. The bioprinter he says will be capable of achieving all the forementioned work is under construction now.

A PERSPECTIVE ON COMING TO SUPPORT LONGEVITY SCIENCE
Monday, November 25, 2013
https://www.fightaging.org/archives/2013/11/a-perspective-on-coming-to-support-longevity-science.php

The most important aspect of our era by far is the prospect for greatly extending healthy life through new medical technology. Long after everything else is forgotten, these years will be remembered as the end of degenerative aging. The new biotechnologies of rejuvenation will only happen rapidly enough to benefit those of use in mid-life if greater funding and attention is given to the best lines of research, however. This is the most important age of mankind, but we ourselves will not greatly benefit from it unless we help move things along more rapidly.

When you are deeply involved in advocacy for longevity science, it is easy to lose your memory of not caring and not knowing. Once upon a time we were all either ignorant or opposed to living longer, as most of the world remains at this time:

On the first Berlin Singularity event when a new friend propositioned the topic of life extension, I was horrified. But then I was even more troubled by the fact that I was horrified. I asked myself to set out the argument for offence. Then one by one, I realised that none of my propositions for concluding that life extension was "insane, gross, disgusting, egotistical" were actually valid. They were all marred by an extreme social and cultural bias.

Just because a thing had always been in such a way, did not mean that it was valid. Just because we had accepted aging in the past as a result of not really having any other choice, did not mean it was valid. Accepting aging was totally illogical - in the same vein that we do not accept cancers, or accidents, or any other cause of mortality. I couldn't find any differences between these diseases and the notion of aging. This wasn't about being 'immortal' (a word I think we all need to shun), but if I loved life (and the lives of those around me), why would I not want to enjoy it, healthier, for as long as I possibly could?

All the money in the world can't stop time from destroying everything. And although we may never absolve ourselves from being under it's grasp in some way or another, we're able now to confront biological time in a way never considered before. We're all racing against internal clockwork. And just like the nobleman taking apart the clock to try and gain control of the one thing that eluded him, so too are longevity research groups taking apart our internal clockwork and examining the mechanism. It's the stuff that humanity has always dreamed of. It's also one of the areas least discussed outside our relatively small circle.

GROWING ARTIFICIAL SKIN FROM UMBILICAL CORD CELLS
Tuesday, November 26, 2013
https://www.fightaging.org/archives/2013/11/growing-artificial-skin-from-umbilical-cord-cells.php

Here is news of one of a number of approaches to building bioartificial skin. As for many organs, a replacement doesn't have to be exactly the same as natural tissue. Rather it just has to be capable of at least some of the functions provided by natural tissue in order to be both beneficial and useful.

Spanish scientists [have] managed, for the first time, to grow artificial skin from stem cells of umbilical cord. [This study] shows the ability of Wharton jelly mesenschymal stem cells to turn to oral-mucosa or skin-regeneration epithelia. To grow the artificial skin, the researchers have used, in addition this new type of epithelia covering, a biomaterial made of fibrin and agarose.

One of the problems major-burn victims currently have is that, in order to apply the current techniques of artificial skin, a number of weeks are needed. That is because the skin needs to be grown from parts of the patient's healthy skin. "Creating this new type of skin using stem cells, which can be stored in tissue banks, means that it can be used instantly when injuries are caused, and which would bring the application of artificial skin forward many weeks."

CELLULAR SENESCENCE IN AGING AS ADAPTED TOOL OF DEVELOPMENT
Tuesday, November 26, 2013
https://www.fightaging.org/archives/2013/11/cellular-senescence-in-aging-as-adapted-tool-of-development.php

An accumulation of senescent cells is one of the causes of degenerative aging. These are damaged or otherwise dysfunctional cells than stop dividing and start issuing signals that are disruptive to surrounding tissues. They should be destroyed by their own programs or by the immune system, but nonetheless accumulate over time, their presence becoming increasingly harmful. Cellular senescence is thought to be a defense against cancer, and as is also the case for the shutting down of stem cell activities with age, this is a defense that bears its cost in terms of increased frailty and tissue failure.

Here researchers argue that the increasing presence of cell senescence with age is a late-life adoption of a mechanism that evolved to steer embryonic development:

Senescent cells are involved in many of the ravages of old age. Wrinkled skin, cataracts and arthritic joints are rife with senescent cells. When researchers rid mice of senescent cells, the animals become rejuvenated. Besides stopping their growth, scientists found, senescent cells also secrete a cocktail of chemicals. The chemicals they release can create chronic inflammation. They also attract certain immune cells, which seek out the senescent cells and kill them.

This behavior can actually be good for our health. As a cell's DNA gets more damaged, it runs a higher risk of dividing uncontrollably and developing into cancer. Senescent cells keep themselves from becoming cancerous by stopping their own growth and by inviting immune cells to kill them. While senescence may be a powerful defense against cancer, however, it comes at a steep cost. Even as we escape cancer, we accumulate a growing supply of senescent cells. The chronic inflammation they trigger can damage surrounding tissue and harm our health.

[Researchers have] confirmed that cells became senescent in many parts of an embryo, such as along the developing tips of the legs. By sheer coincidence [they] had also discovered senescent cells in other regions of the embryo, such as the middle ear. The researchers found no evidence that the senescent cells in embryos have damaged DNA. That discovery raises the question of how the cells were triggered to become senescent. [It is hypothesized] they did so in response to a signal from neighboring cells.

Once an embryonic cell becomes senescent, it does the two things that all senescent cells do: it stops dividing and it releases a special cocktail. The new experiments suggest that this cocktail plays a different role in the embryo than in the adult body. It may act as a signal to other cells to become different tissues. It may also tell those tissues to grow at different rates into different shapes. [Researchers suspect] that the sculpting that senescent cells carry out may be crucial to the proper development of an embryo. It's possible [that] senescence actually evolved first as a way to shape embryos; only later in evolution did it take on a new role, as a weapon against cancer.

REGULAR EXERCISE CORRELATES WITH BETTER LONG TERM HEALTH
Wednesday, November 27, 2013
https://www.fightaging.org/archives/2013/11/regular-exercise-correlates-with-better-long-term-health.php

Here is a study that provides more data to strengthen the already well-proven correlation between regular exercise and long-term health:

Physical activity is associated with improved overall health in those people who survive to older ages, otherwise conceptualised as healthy ageing. Previous studies have examined the effects of mid-life physical activity on healthy ageing, but not the effects of taking up activity later in life. We examined the association between physical activity and healthy ageing over 8 years of follow-up.

Participants were 3454 initially disease-free men and women (aged 63.7±8.9 years at baseline) from the English Longitudinal Study of Ageing, a prospective study of community dwelling older adults. Self-reported physical activity was assessed at baseline (2002-2003) and through follow-up. Healthy ageing, assessed at 8 years of follow-up (2010-2011), was defined as those participants who survived without developing major chronic disease, depressive symptoms, physical or cognitive impairment.

At follow-up, 19.3% of the sample was defined as healthy ageing. In comparison with inactive participants, moderate, or vigorous activity at least once a week was associated with healthy ageing, after adjustment for age, sex, smoking, alcohol, marital status and wealth. Becoming active or remaining active was associated with healthy ageing in comparison with remaining inactive over follow-up. Sustained physical activity in older age is associated with improved overall health. Significant health benefits were even seen among participants who became physically active relatively late in life.

A REVIEW OF NATURAL MECHANISMS FOR REMOVING TAU
Wednesday, November 27, 2013
https://www.fightaging.org/archives/2013/11/a-review-of-natural-mechanisms-for-removing-tau.php

Like the better known amyloid-beta, the protein tau accumulates in Alzheimer's disease, and there is still much debate over exactly how this relates to damage and dysfunction. A fair portion of Alzheimer's research now focuses on clearance of amyloid and tau, often through immune therapies. We can hope that this produces technology platforms that can be turned to the removal of other forms of amyloid and unwanted proteins known to build up in old tissue. Here is an open access review that looks over what is presently known of the existing natural mechanisms that work to clear tau:

One of the defining pathological features of Alzheimer disease (AD) is the intraneuronal accumulation of tau. The tau that forms these accumulations is altered both posttranslationally and conformationally, and there is now significant evidence that soluble forms of these modified tau species are the toxic entities rather than the insoluble neurofibrillary tangles. However there is still noteworthy debate concerning which specific pathological forms of tau are the contributors to neuronal dysfunction and death in AD.

Given that increases in aberrant forms of tau play a role in the neurodegeneration process in AD, there is growing interest in understanding the degradative pathways that remove tau from the cell, and the selectivity of these different pathways for various forms of tau. Indeed, one can speculate that deficits in a pathway that selectively removes certain pathological forms of tau could play a pivotal role in AD.

In this review we will discuss the different proteolytic and degradative machineries that may be involved in removing tau from the cell. How deficits in these different degradative pathways may contribute to abnormal accumulation of tau in AD will also be considered. In addition, the issue of the selective targeting of specific tau species to a given degradative pathway for clearance from the cell will be addressed.

RAY KURZWEIL AND RADICAL LIFE EXTENSION
Thursday, November 28, 2013
https://www.fightaging.org/archives/2013/11/ray-kurzweil-and-radical-life-extension.php

I have long found it curious that Ray Kurzweil's public position on radical life extension omits support of specific ongoing research aimed at producing therapies for aging, such as the SENS program of rejuvenation biotechnology. This may be because he prefers to think in terms of broader trends rather than try to pick winners from present initiatives. Alternatively it may be because he sees the machine phase of medicine - the use of swarms of nanorobots capable of maintaining or replacing our biology - as emerging sooner rather than later.

As for me, I don't think that an early arrival of machine phase medicine is plausible: from where I stand it looks as though the medicine of the next four decades will be almost entirely based on control and manipulation of cells, alongside the design of proteins that complement our existing evolved set of protein machinery. We will augment and direct our own molecular biology using more molecular biology for decades before we get to the point of designing and using nanomachines that are as complex as cells without being biological at all.

So programs that are logical outgrowths of present day medicine - like SENS, pushing for repair therapies for cells and clearance of waste products - are the next step in human longevity. It's not a matter of skipping straight to nanorobotic cell replacements of the sort envisaged by Robert Freitas and others.

Most of us accept that our lives are limited. We'll have a certain number of years - more than 75, we hope, but probably fewer than 100 - and then we'll die. The world will go on without us. An awareness of our own mortality, we tell ourselves, is part of what makes is human. Not Ray Kurzweil. A renowned computer scientist and inventor, Kurzweil, 65, decided decades ago that mortality wasn't for him. He didn't have to die, and he wasn't going to, if he could help it. Fortunately, he believes he can help it - and he's been working feverishly at the task of staying alive ever since.

"How long do you think you will live?" I asked Kurzweil in a recent phone interview. He rarely misses a beat in conversation, but he was quiet for just a moment before replying. "I think I have a good chance - I would put it at 80 percent - of getting to the point where it becomes indefinite, because you'll be adding more time than is going by to your remaining life expectancy."

Technological advances won't transpire steadily over time, but rather exponentially, so that each year brings more change than the last. In fact, this is what's been happening for decades in the realm of computer processors, where it's known as Moore's law. Kurzweil believes similar laws of accelerating growth govern all forms of information technology. And he believes that all technology will eventually become a form of information technology. Ergo, technological progress is about to get really, really fast.

So why hasn't average life expectancy - or even the age of the oldest human alive - budged much over the last few decades? Kurzweil says we're just approaching what he calls "the knee of the curve." That's the point at which an exponential function starts to rocket upward. Longevity, Kurzweil explains, "is going to transform from having been a hit-or-miss affair where progress was linear ... to where it is now an information technology and therefore subject to my law of accelerating returns."

MULTIPLE METHODS OF REGENERATION IN SIMILAR SALAMANDER SPECIES
Thursday, November 28, 2013
https://www.fightaging.org/archives/2013/11/multiple-methods-of-regeneration-in-similar-salamander-species.php

Researchers have for some years been investigating the mechanisms by which salamanders can regenerate limbs and organs. The hope is that either this capacity still exists in mammals in some form, dormant but able to be reactivated, or otherwise that there is something to be learned from salamander biology that might be imported to mammals to create greater feats of regeneration.

This latest research might go some way to explaining some of the contradictory results that have emerged from past work on the biology of salamander regeneration, such as whether or not their regenerative capacity declines with age:

Scientists labelled different cell types in two species of salamander in order to ascertain what kinds of cell give rise to new muscle tissue in salamanders that had lost a front leg. Salamanders are known for their remarkable ability to regenerate not only lost tails and other extremities but also the tissue of internal organs, such as the heart and brain. The traditional view is that the new tissue is formed from a population of stem cells activated when body parts are damaged; what they found, however, was that even though the two species were relatively closely related, this was true only for one.

"We show that in one of the salamander species, muscle tissue is regenerated from specialised muscle cells that dedifferentiate and forget what type of cell they've been. This is an interesting cellular mechanism that destabilises cell specialisation and produces new stem cells, as opposed to the other species, in which the new muscles are created from existing stem cells."

In the dedifferentiating species, the capacity to regenerate tissue does not decline with age, which the scientists believe can be linked to their ability to make new stem cells from muscle cells on demand. "It's important to study the process by which the salamander's muscle cells forget their cellular identity and how its modulated. It's also important to examine why their ability to regenerate is independent of age and the number of times the same tissue and body part has been regenerated."

CORRELATIONS WITH SPECIES LONGEVITY FOUND IN THE LIPIDOME
Friday, November 29, 2013
https://www.fightaging.org/archives/2013/11/correlations-with-species-longevity-found-in-the-lipidome.php

The membrane pacemaker hypothesis suggests that one of the most important links between biology and longevity is the composition of cell and organelle membranes. If membranes are more resistant to oxidative damage then the result will be greater longevity. Differing levels of resistance can emerge in different species because of differing proportions of various lipids that make up membrane structures: some lipids are less vulnerable to peroxidation than others. Here, researchers demonstrate a good correlation between lipid profiles and longevity:

Membrane lipid composition is an important correlate of the rate of aging of animals and, therefore, the determination of their longevity. In the present work, the use of high-throughput technologies allowed us to determine the plasma lipidomic profile of 11 mammalian species ranging in maximum longevity from 3.5 to 120 years. The non-targeted approach revealed a species-specific lipidomic profile that accurately predicts the animal longevity.

The regression analysis between lipid species and longevity demonstrated that the longer the longevity of a species, the lower is its plasma long-chain free fatty acid (LC-FFA) concentrations, peroxidizability index, and lipid peroxidation-derived products content. The inverse association between longevity and LC-FFA persisted after correction for body mass and phylogenetic interdependence. These results indicate that the lipidomic signature is an optimized feature associated with animal longevity, emerging LC-FFA as a potential biomarker of longevity.

A LOOK AT LIPID REPLACEMENT THERAPY
Friday, November 29, 2013
https://www.fightaging.org/archives/2013/11/a-look-at-lipid-replacement-therapy.php

There has been more interest of late in how to engineer ways to sneak useful proteins past the digestive system so that they can be added to the diet but still find their way into cells. Researchers here combine this with the idea that you can dilute the proportion of damaged lipids present in cell membranes by providing a patient with a supply of undamaged lipids, larger than the body would otherwise generate on its own. I am not familiar enough with this line of work to be able to comment on how useful it is in practice, or whether the balance of evidence suggests that the observed results in trials actually occur due to the replacement of damaged lipids, as the authors state below. It is nonetheless quite interesting in the context of the membrane pacemaker hypothesis:

Lipid Replacement Therapy, the use of functional oral supplements containing cell membrane phospholipids and antioxidants, has been used to replace damaged, usually oxidized, membrane glycerophospholipids that accumulate during aging and in various clinical conditions in order to restore cellular function.

This approach differs from other dietary and intravenous phospholipid interventions in the composition of phospholipids and their defense against oxidation during storage, ingestion, digestion and uptake as well as the use of protective molecules that noncovalently complex with phospholipid micelles and prevent their enzymatic and bile disruption.

Once the phospholipids have been taken in by transport processes, they are protected by several natural mechanisms involving lipid receptors, transport and carrier molecules and circulating cells and lipoproteins until their delivery to tissues and cells where they can again be transferred to intracellular membranes by specific and nonspecific transport systems. Once delivered to membrane sites, they naturally replace and stimulate removal of damaged membrane lipids.

Various chronic clinical conditions are characterized by membrane damage, mainly oxidative but also enzymatic, resulting in loss of cellular function. This is readily apparent in mitochondrial inner membranes where oxidative damage to phospholipids like cardiolipin and other molecules results in loss of trans-membrane potential, electron transport function and generation of high-energy molecules. Recent clinical trials have shown the benefits of Lipid Replacement Therapy in restoring mitochondrial function and reducing fatigue in aged subjects and patients with a variety of clinical diagnoses that are characterized by loss of mitochondrial function and include fatigue as a major symptom.