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More Recent Coverage of SENS Research – Article by Reason

More Recent Coverage of SENS Research – Article by Reason

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The New Renaissance Hat
Reason
January 31, 2014
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SENS stands for the Strategies for Engineered Negligible Senescence, a research and development plan first assembled more than a decade ago by biomedical gerontologist Aubrey de Grey. This was a work of vision and synthesis: taking decades of research results from many diverse fields of medical research whose scientists had comparatively little contact with one another, and little interest in working on ways to treat aging, and pulling these results together into a convincing argument as to (a) which forms of cellular and molecular damage cause aging, and (b) how to go about developing the means of repair for this damage.

Aging is damage, and repair is rejuvenation. Sufficiently comprehensive implementations of SENS should not only prevent aging and age-related disease, but also reverse the effects of aging in the old. This isn’t a matter of hand-waving: the capabilities in molecular biology and research plans to build therapies are outlined in considerable detail at the SENS Research Foundation website and in related scientific papers. You should take a look if you haven’t recently. The estimated cost of developing this to the point of demonstration in mice is on a par with the total cost of development of a single drug: perhaps $1-2 billion over 10-20 years.

It is pleasing to chart the changing character of press coverage over the years for SENS rejuvenation research and its figurehead advocate and organizer Aubrey de Grey. In the past ten years of increasing support within the scientific community and an influx of millions of dollars in philanthropic funding for research, it has become ever harder for journalists to stick their heads in the sand and pretend that SENS is either fringe or not real science. The gatekeepers of the establishment are never kind to any form of change or progress in the early days.

Measured by budget the SENS Research Foundation is a presently a tenth of the size of the well-established and mainstream Buck Institute for Aging Research. This is still larger than a good many labs in the field, and funding for SENS research has grown considerably over the past few years. Skilled molecular biologists in numerous laboratories are working on aspects of the SENS program of development for rejuvenation therapies. This work is still at the level of building tools and foundations for later progress, but it is very much real, tangible medical research. This is a new and upcoming field, the future of medical science and aging.

Aubrey de Grey: Out to Defy Death

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Spend a moment asking yourself, “What is the world’s worst problem?”

Biomedical gerontologist Aubrey de Grey, Ph.D., has an answer that may be radically different from yours. For him, it’s aging, and he not only makes a convincing case for why this is so, but he’s devoting his life to doing something about it. Dr. de Grey is the founder of SENS, a research foundation that aims to help build the regenerative medicine industry, an industry that arguably has the best chance for curing the diseases of aging. Surprisingly, he’s having more success than the people who were calling him a maverick and a heretic five years ago ever imagined.

First they ignore you, then they laugh at you, then they fight you, then you win. To my eyes, things have made it to the early stages of the winning part of that saying these days, certainly insofar as the scientific community is concerned. (Much more remains to be done in order to sell the public on the idea that radical life extension is a real possibility and that the relevant research is important and should be supported.) SENS is far more than Aubrey de Grey nowadays: it’s his vision, but has grown to be shared quite widely. There are dozens of influential allied scientists and laboratories, a number of high-net-worth philanthropists providing support, many advocates, a SENS Research Foundation staff, fundraisers, and, of course, the numerous researchers working to build the tools needed for future rejuvenation treatments.

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The SENS Foundation is a public charity based in California, and its purpose is to fill a niche in the research funding chain. Private sector research, particularly in the drug industry, has funds to drive important research, but only after it’s clear that the odds of success are good, the time frame is reasonably short, and the potential for profit large. At the other end of the research spectrum, public sector research funding is available for basic research that doesn’t have an immediate commercial purpose.

However, in Dr. de Grey’s view, and his colleagues’ as well, there’s a midway point between the private sector funding and the public sector, and this midpoint is often neglected. Research that may yield incalculable commercial success (and public benefit as well), may be at such an early stage of development that it doesn’t yet attract commercial funders. “We exist to make sure that this kind of intermediate research is not neglected,” he says.

People no longer refer to Aubrey de Grey as a “maverick” or “heretic.” “These days, I’m more often called ‘controversial,'” he says, sounding pleased with this new characterization.

“Controversial,” after all can be translated as, “might be right.”

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries. 

This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.

A Simpler Path to Creating Pluripotent Stem Cells – Article by Reason

A Simpler Path to Creating Pluripotent Stem Cells – Article by Reason

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The New Renaissance Hat
Reason
January 31, 2014
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An improvement on current methods of creating pluripotent stem cells has been in the news the past few days. It involves stressing cells with simple mechanisms, and is straightforward enough that I hear numerous laboratories and individual researchers have started in on trying it out immediately, as well as revisiting other variants of stressing cells to see what the outcome might be. The methodology is something that DIYbio enthusiasts could carry out as a weekend project with minimal cost and equipment, which is a great improvement over prior standard methods involving delivery of genes or similar operations.

As with all such potential infrastructure improvements, one pillar of importance is the reduction in cost and difficulty of research. When someone figures out a much cheaper way of achieving any particular goal, all further work that builds on that goal moves more rapidly: existing groups can do more, and new groups that previously couldn’t afford to join in now start work. Cell pluripotency is near the base of regenerative medicine and tissue engineering: ways to better achieve it accelerate the whole field.

As you can see, there are also other ramifications, however, such as for persistent reports of pluripotent stem cells isolated from adult tissues – VSELs and others – and the debate over difficulties in replicating that research.

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In 2006, Japanese researchers reported a technique for creating cells that have the embryonic ability to turn into almost any cell type in the mammalian body – the now-famous induced pluripotent stem (iPS) cells. In papers published this week, another Japanese team says that it has come up with a surprisingly simple method – exposure to stress, including a low pH – that can make cells that are even more malleable than iPS cells, and do it faster and more efficiently.

“It’s amazing. I would have never thought external stress could have this effect,” says Yoshiki Sasai. It took Haruko Obokata, a young stem-cell biologist at the same centre, five years to develop the method and persuade Sasai and others that it works. “Everyone said it was an artefact – there were some really hard days.”

The results could fuel a long-running debate. For years, various groups of scientists have reported finding pluripotent cells in the mammalian body. But others have had difficulty reproducing such findings. Obokata started the current project by looking at cells thought to be pluripotent cells isolated from the body. But her results suggested a different explanation: that pluripotent cells are created when the body’s cells endure physical stress.

Obokata has already reprogrammed a dozen cell types, including those from the brain, skin, lung and liver, hinting that the method will work with most, if not all, cell types. On average, she says, 25% of the cells survive the stress and 30% of those convert to pluripotent cells – already a higher proportion than the roughly 1% conversion rate of iPS cells.

Link: http://www.nature.com/news/acid-bath-offers-easy-path-to-stem-cells-1.14600

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries. 

This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.

Gennady and Wendy Stolyarov’s Forthcoming Presentation on “Death is Wrong” at Transhuman Visions 2.0

Gennady and Wendy Stolyarov’s Forthcoming Presentation on “Death is Wrong” at Transhuman Visions 2.0

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I invite all of my readers to join me at the Transhuman Visions 2.0 East Bay conference in Piedmont, CA, on Saturday, March 1, 2014. I will be there with my wife Wendy Stolyarov to deliver the opening presentation about Death is Wrong, our new ambitious illustrated children’s book on indefinite life extension. For a prelude to my presentation, I invite you to read my article, “Why I Wrote a Children’s Book on Indefinite Life Extension“. Also, autographed copies of Death is Wrong will be available for sale.

The Transhuman Visions 2.0 East Bay conference is produced by the Brighter Brains Institute and its energetic, prolific, and creative founder, Hank Pellissier. For detailed information about the conference, see the official Brighter Brains Institute page here.

The poster for this event was designed by none other than Wendy Stolyarov. It is a testament to her skill in graphic design and the new standard of excellence her art brings to the transhumanist movement.

Transhuman Visions 2.0 East Bay – Poster by Wendy Stolyarov
Technological Singularities: An Overview – Video by G. Stolyarov II

Technological Singularities: An Overview – Video by G. Stolyarov II

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Mr. Stolyarov explains the basic concept of a technological Singularity and his understanding that humankind has already experienced three such Singularities in the form of the Agricultural, Industrial, and Information Revolutions. The next Singularity will come about due to a convergence of technologies such as artificial intelligence, nanotechnology, and biotechnology (including indefinite life extension).

Pioneers on Time’s Trail – Article by Eric Schulke

Pioneers on Time’s Trail – Article by Eric Schulke

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The New Renaissance Hat
Eric Schulke
January 5, 2014
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The universe, the cities, the souls, times come and past, the big picture of it all, its fortune and fate, happenstance and chance coiling through the airwaves, weaving in and out throughout the corridors and shores and floors… We call it existence, and it’s big, really big.

History’s timeline is like a long path, and we here represent the spot on that trail that time is currently manifested as. The stars in the background are the only imprint remaining that spans history’s trail of mementos, like Dachau death marches and Choctaw trails. Even relics continue the slide as they slowly fade, mountains of their days, now chiseled away by time’s currents.

It’s all wild, legendary, mythical, incredible, and ours – each one of ours. There are worlds of complex mechanisms inside atoms, inside cells, inside creatures, inside ecosystems, on planets, in galaxies, and on and on, leaving us wondering if it really could be like an endless fractal in both directions, and desperate for a chance to know. The long, arduous labors of our prokaryotic precursors are now beginning to bud curious new transhuman fruit. Each one of us materializes on the timeline of humanity, like rickety roller coasters set up on temporary take-down stages for traveling theater, just hoping to stay on the tracks. We have conquered a planet under these circumstances. Like Alexander the Great crossing countries atop Bucephalus, we ride through the universe atop the planet Earth, trying to keep our grip on the reins while we hop from stage to stage.

Not even a percent of a percent of this territory is mapped. What does that mean for all that is outside of the speck of light we are in so far? Trillions upon trillions upon trillions of lives and scenarios are interacting and going down around us every day. You might see an ant fighting with a mutant form of a June bug and be able to contemplate their struggle, but miss the fact that this mutation will soon change the landscape of the area in profound ways. You might just dirt-bike right over the top of them without ever even contemplating that, all the while thinking about the prospects of a ranch-style house in this area and the philosophy of a progressive struggle in a capitalist climate. All this occurs while unknowns surround us. Maybe an unfathomable machine is being created on a planet whose distance we can’t conceive, illuminating answers we never dreamt possible. Maybe an amazingly complex civilization is at its height. Perhaps there are other dimensions with wonders that would blow our minds while they’re blowing our minds.

The poorest among the industrialized citizens today still have their “junky” cars, and stereos, lighters, cell phones, watches (scratch that, clocks are on cell phones now), 3 TVs with “only” 8 basic channels, “old” computers and “slow” internet connections, FDA-tested food, state-of-the-art health technology with emergency transport, malls and restaurants just down the street, the freedom to fly anywhere in the world after a few weeks’ saving, and so many other things. These are our poorest people. They are richer than the richest kings and queens of old. In the same kind of way that the poorest among us today have many times more than the richest kings and queens of centuries ago, so will the poorest of us in a post-definite lifespan world be richer than the richest Forbes List billionaire among us today.

Think of the ancient history: the richest of the kings and queens with the golden thrones, crowns, everything jewel-encrusted, exotic animals, limitless concubines, slaves, best fish tank, singing canaries, speedy buggies, salted turnips, and best open-hole bathroom that money could buy. What is that money worth to them now? Time is money, and if you don’t have any, then you’re dead broke.

Some of these ancients remain with us as mummies today. Now there’s an interesting collision of worlds. Those who could still be here, who want to be here, gave it their best shot, and are still here, now in rags begging for us to come up with a solution to bring them back to life. It was a nice try. Their notions lived on in the DNA of their progeny, working it out, better and better, building the tools and emerging today among us as cryonics, a surer form of mummification. We don’t have the cures or the salves for the mummies, but you still have a shot. You are them; you are the same people, the same blood; you are the ancients, but the future can still be theirs/yours. 1,000 BC, 2,100 AD – it’s all ancient history to the people of 45,000 AD.

We know what is going on in parts of this place we are in, but what about everywhere else? What about how it all interacts? What it all means as a whole? Do we think we can guess what is going on everywhere? We can hardly ever even guess who the culprit is in a typical television murder mystery. Can we even guess what is going on in all the buildings of one single town? Some of those points of light in the nighttime sky are entire galaxies unto themselves. Some of them are entire universes. That space between might not end.

This paper could be expanded to fill libraries with volumes on the limitless and profound, mind-blowing, unencapsulatable nature of it. No, libraries are filled with volumes on exactly that, and even those haven’t begun to scratch the surface of what it means to exist.

So here we are, pioneers on time’s trail, the precursors, surviving caravans retooling for a star trek. What does the big picture of existence have in store for us on the trail ahead?

Eric Schulke was a director at LongeCity during 2009-2013. He has also been an activist with the Movement for Indefinite Life Extension and other causes for over 13 years.

Why Prioritize SENS Research for Human Longevity? – Article by Reason

Why Prioritize SENS Research for Human Longevity? – Article by Reason

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The New Renaissance Hat
Reason
December 29, 2013
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Why do I vocally support rejuvenation research based on the Strategies for Engineered Negligible Senescence (SENS) over other forms of longevity science? Why do I hold the view that SENS and SENS-like research should be prioritized and massively funded? The short answer to this question is that SENS-derived medical biotechnology has a much greater expected utility – it will most likely produce far better outcomes, and at a lower cost – than other presently ongoing lines of research into creating greater human longevity.

What is SENS?

But firstly, what is SENS? It is more an umbrella collection of categories than a specific program, though it is the case that narrowly focused SENS research initiatives run under the auspices of the SENS Research Foundation. On the science side of the house, SENS is a synthesis of existing knowledge from the broad mainstream position regarding aging and the diseases of aging: that aging is caused by a stochastic accumulation of damage at the level of cells and protein machinery in and around these cells. SENS is a proposal, based on recent decades of research, as to which of the identified forms of damage and change in old tissues are fundamental – i.e. which are direct byproducts of metabolic operation rather than cascading effects of other fundamental damage. On the development side of the house, SENS pulls together work from many subfields of medical research to show that there are clear and well-defined ways to produce therapies that can repair, reverse, or make irrelevant these fundamental forms of biological damage associated with aging.

(You can read about the various forms of low-level damage that cause aging at the SENS Research Foundation website and elsewhere. This list includes: mitochondrial DNA mutations; buildup of resilient waste products inside and around cells; growing numbers of senescent and other malfunctioning cells; loss of stem cells; and a few others).

Present arguments within the mainstream of aging research are largely over the relative importance of damage type A versus damage type B, and how exactly the extremely complex interaction of damage with metabolism progresses – but not what that damage actually is. A large fraction of modern funding for aging research goes towards building a greater understanding this progression; certainly more than goes towards actually doing anything about it. Here is the thing, however: while understanding the dynamics of damage in aging is very much a work in progress, the damage itself is well known. The research community can accurately enumerate the differences between old tissue and young tissue, or an old cell and a young cell – and it has been a good number of years since anything new was added to that list.

If you can repair the cellular damage that causes aging, it doesn’t matter how it happens or how it affects the organism when it’s there. This is the important realization for SENS – that much of the ongoing work of the aging research community is largely irrelevant if the goal is to get to human rejuvenation as rapidly as possible. Enough is already known of the likely causes of aging to have a reasonable expectation of being able to produce laboratory demonstrations of rejuvenation in animal models within a decade or two, given large-scale funding.

Comparing Expected Values

Expected value drives human endeavor. What path ahead do we expect to produce the greatest gain? In longevity science the investment is concretely measured in money and time, and we might think of the expected value in terms of years of healthy life added by the resulting therapies. The cost of these therapies really isn’t much of a factor – all major medical procedures and other therapies tend to converge to similar costs over time, based on their category: consider a surgery versus an infusion versus a course of pills, for example, where it’s fairly obvious that the pricing derives from how much skilled labor is involved and how much care the patient requires as a direct result of the process.

On the input side, there are estimates for the cost in time and money to implement SENS therapies for laboratory mice. For the sake of keeping things simple, I’ll note that these oscillate around the figures of a billion dollars and ten years for the crash program of fully-funded research. A billion dollars is about the yearly budget of the NIA these days, give or take, which might be a third of all research funding directed towards aging – by some estimates, anyway, though this is a very hard figure to verify in any way. It’s by no means certain the that the general one-third/two-thirds split between government and private research funding extends to aging research.

On the output side, early SENS implementations would be expected to take an old mouse and double its remaining life expectancy – e.g. produce actual rejuvenation, actual repair, and reversal of the low-level damage that causes aging, with repeated applications at intervals producing diminishing but still measurable further gains. This is the thing about a rejuvenation therapy that works; you can keep on applying it to sweep up newly accruing damage.

So what other longevity science do we have to compare against? The only large running programs are those that have grown out of the search for calorie-restriction mimetic drugs. So there is the past decade or so of research into sirtuins, and there is growing interest in mTOR and rapamycin analogs that looks to be more of the same, but slightly better (though that is a low bar to clear).

In the case of sirtuins, money has certainly flowed. Sirtris itself sold for ~$700 million, and it’s probably not unreasonable to suggest that a billion dollars have gone into broader sirtuin-related research and development over the past decade. What does the research community have to show for that? Basically nothing other than an increased understanding of some aspects of metabolism relating to calorie restriction and other adaptations that alter lifespan in response to environmental circumstances. Certainly no mice living longer in widely replicated studies as is the case for mTOR and rapamycin – the sirtuin results and underlying science are still much debated, much in dispute.

The historical ratio of dollars to results for any sort of way to manipulate our metabolism to slow aging is exceedingly poor. The thing is, this ratio shouldn’t be expected to get all that much better. Even if marvelously successful, the best possible realistic end result of a drug that slows aging based on what is known today – say something that extracts the best side of mTOR manipulation with none of the side-effects of rapamycin – is a very modest gain in human longevity. It can’t greatly repair or reverse existing damage, it can’t much help those who are already old become less damaged, it will likely not even be as effective as actual, old-fashioned calorie restriction. The current consensus is that calorie restriction itself is not going to add more than a few years to a human life – though it certainly has impressive health benefits.

(A sidebar: we can hope that one thing that ultimately emerges from all this research is an explanation as to how humans can enjoy such large health benefits from calorie restriction, commensurate with those seen in animals such as mice, without also gaining longer lives to match. But if just eating fewer calories while obtaining good nutrition could make humans reliably live 40% longer, I think that would have been noted at some point in the last few thousand years, or at least certainly in the last few hundred).

From this perspective, traditional drug research turned into longevity science looks like a long, slow slog to nowhere. It keeps people working, but to what end? Not producing significant results in extending human longevity, that’s for sure.

Ergo…

The cost of demonstrating that SENS is the right path or the wrong path – i.e. that aging is simply an accumulation of damage, and the many disparate research results making up the SENS vision are largely correct about which forms of change in aged tissue are the fundamental forms of damage that cause aging – is tiny compared to the cost of trying to safely eke out modest reductions in the pace of aging by manipulating metabolism via sirtuins or mTOR.

The end result of implementing SENS is true rejuvenation if aging is caused by damage: actual repair, actual reversal of aging. The end result of spending the same money and time on trying to manipulate metabolism to slow aging can already be observed in sirtuin research, and can reasonably be expected to be much the same the next time around the block with mTOR – it produces new knowledge and little else of concrete use, and even when it does eventually produce a drug candidate, it will likely be the case that you could do better yourself by simply practicing calorie restriction.

The expectation value of SENS is much greater than that of trying to slow aging via the traditional drug-discovery and development industry. Ergo the research and development community should be implementing SENS. It conforms to the consensus position on what causes aging, it costs far less than all other proposed interventions into the aging process, and the potential payoff is much greater.

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries. 

This work is reproduced here in accord with a Creative Commons Attribution license.  It was originally published on FightAging.org.

A Brace of Papers from the Longevity Genetics Community – Article by Reason

A Brace of Papers from the Longevity Genetics Community – Article by Reason

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The New Renaissance Hat
Reason
December 29, 2013
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You’ll find quite a few papers on longevity and genetics in the preprint queue of Current Vascular Phamacology at the moment. This is a portion of the output of that part of the research community focused on developing a full understanding of the molecular biology of how aging progresses and varies between individuals and species. Biology is fantastically complex, and obtaining that full understanding will be a much, much more challenging endeavor than merely successfully treating or reversing aging.

Treating and even curing aging are goals that might be achieved without a full understanding of exactly how aging progresses. Consider this: you don’t need anything even close to a full molecular model of the progression of rust to greatly extend the life of metal equipment through scrubbing and protective coating. Exactly the same argument about knowledge and action can be applied to biology and medicine. Knowing what the damage is and having a complete understanding of how that damage progresses to cause the visible symptoms of aging are two very different things, the latter much more complex than the former, and only the former actually needed to produce useful therapies.

Nonetheless, most of the present work and funding in the aging science community is focused on developing an understanding of how degenerative aging progresses, not on damage repair and treatment of aging. So most of the output of the research community looks much along the lines of these first few papers I’m going to point out today.

The Challenges in Moving from Ageing to Successful Longevity

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During the last decades survival has significantly improved and centenarians are becoming a fast-growing group of the population. Genetic factors contribute to the variation of human life span by around 25%, which is believed to be more profound after 85 years of age. It is likely that multiple factors influence life span and we need answers to questions such as: 1) What does it take to reach 100?, 2) Do centenarians have better health during their lifespan compared with contemporaries who died at a younger age?, 3) Do centenarians have protective modifications of body composition, fat distribution and energy expenditure, maintain high physical and cognitive function, and sustained engagement in social and productive activities?, 4) Do centenarians have genes which contribute to longevity?, 5) Do centenarians benefit from epigenetic phenomena?, 6). Is it possible to influence the transgenerational epigenetic inheritance (epigenetic memory) which leads to longevity?, 7) Is the influence of nutrigenomics important for longevity?, 8) Do centenarians benefit more from drug treatment, particularly in primary prevention?, and, 9) Are there any potential goals for drug research?

Genes Of Human Longevity: An Endless Quest?

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Human longevity is a complex trait which genetics, epigenetics, environmental and stochasticity differently contribute to. To disentangle the complexity, our studies on genetics of longevity were, at the beginning, mainly focused on the extreme phenotypes, i.e. centenarians who escaped the major age-related diseases compared with cross sectional cohorts.

In association studies on candidate genes many SNPs, positively or negatively correlated with longevity have been identified. On the other hand, the identification of longevity-related genes does not explain the mechanisms of healthy aging and longevity, but it opens a huge amount of questions on epigenetic contribution, gene regulation and the interactions with essential genomes, i.e. mitochondrial DNA and microbiota.

Centenarian Offspring: a model for Understanding Longevity

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A main objective of current medical research is the improving of life quality of elderly people as priority of the continuous increase of ageing population. Accordingly, the research interest is focused on understanding the biological mechanisms involved in determining the positive ageing phenotype, i.e. the centenarian phenotype. Centenarians have been used as an optimal model for successful ageing. However, it is characterized by several limitations, i.e. the selection of appropriate controls for centenarians and the use itself of the centenarians as a suitable model for healthy ageing. Thus, the interest has been centered on centenarian offspring, healthy elderly people. They may represent a model for understanding exceptional longevity for the following reasons: to exhibit a protective genetic background, cardiovascular and immunological profile as well as a reduced rate of cognitive decline than age-matched people without centenarian relatives.

Phenotypes and Genotypes of High Density Lipoprotein Cholesterol in Exceptional Longevity

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A change in the lipoprotein profile is a metabolic hallmark of aging and has been the target for modern medical developments. Although pharmaceutical interventions aimed at lipid lowering substantially decrease the risk of cardiovascular disease, they have much less impact on mortality and longevity. Moreover, they have not affected death from other age-related diseases.

In this review we focus on high density lipoprotein (HDL) cholesterol, the levels of which are either elevated or do not decrease as would be expected with aging in centenarians, and which are associated with lower prevalence of numerous age-related diseases; thereby, suggesting a potential HDL-mediated mechanism for extended survival. We also provide an update on the progress of identifying longevity-mediating lipid genes, describe approaches to discover longevity genes, and discuss possible limitations. Implicating lipid genes in exceptional longevity may lead to drug therapies that prevent several age-related diseases, with such efforts already on the way.

It has to be said, however, that some areas of research are close enough to the development of actual rejuvenation treatments – those addressing at least some of the root cause damage of aging rather than downstream consequences – that even the scientific mainstream is coming around to the idea. The impact of cellular senescence on aging is one such field, as several obvious and existing applications of medical technology may aid in removal of the senescent cells that accumulate with age, and early work in mice confirms that such treatments should prove helpful:

Cellular Senescence in Ageing, Age-Related Disease and Longevity

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Cellular senescence is the state of permanent inhibition of cell proliferation. There is mounting evidence that senescent cells contribute to ageing and age-related disease by generating a low grade inflammation state (senescence-associated secretory phenotype-SASP). Even though cellular senescence is a barrier for cancer it can, paradoxically, stimulate development of cancer via proinflammatory cytokines. There is evidence that senescent vascular cells, both endothelial and smooth muscle cells, participate in atherosclerosis and senescent preadipocytes and adipocytes have been shown to lead to insulin resistance.

Thus, modulation of cellular senescence is considered as a potential pro-longevity strategy. It can be achieved in several ways like: elimination of selected senescent cells, epigenetic reprogramming of senescent cells, preventing cellular senescence or influencing the secretory phenotype. Some pharmacological interventions have already been shown to have promising activity in this field.

 

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries. 

This work is reproduced here in accord with a Creative Commons Attribution license.  It was originally published on FightAging.org.

Why I Wrote a Children’s Book on Indefinite Life Extension – Article by G. Stolyarov II

Why I Wrote a Children’s Book on Indefinite Life Extension – Article by G. Stolyarov II

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The New Renaissance Hat
G. Stolyarov II
December 21, 2013
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My greatest fear about the future is not of technology running out of control or posing existential risks to humankind. Rather, my greatest fear is that, in the year 2045, I will be 58 years old and already marked by notable signs of senescence, sitting at the kitchen table, drinking my morning coffee, and wondering, “What happened to that Singularity we were promised by now? Why did it not come to pass? Why does the world of 2045 look pretty much like the world of 2013, with only a few cosmetic differences?” My greatest fear is that, as I stare into that mug of coffee, I would recognize that it will all be downhill from there, especially as “kids these days” would pay no more attention to technological progress and life-extension possibilities than their predecessors did. My greatest fear is that they would consider me a quixotic old man, fantasizing about a future that never was, while they struggle to make ends meet in an ever-more hostile economy (which would look much like our own, except farther along in the sequence of gradual decay, because nobody cares), strangled by labyrinthine restrictions arising out of Luddism and change-aversion within the widespread society. In short, my greatest fear is that our present will be our future, except that I and the present generation of longevity activists will lose our youthful vitality and will ourselves be rapidly approaching the abyss of oblivion.

So I needed to do something. I am not a doctor or biologist, but I did vow at the age of five that I would devote my life to the struggle against senescence and death – so I needed to make good on that promise. My articles, videos, and occasional donations to life-extension endeavors are all well and good, but I also wanted to make a unique contribution that could turn the tide of cultural attitudes toward life extension and toward death itself. After years of brainstorming and months of concerted activity on the part of both me and my wife and illustrator Wendy Stolyarov, the result is Death is Wrong – an illustrated children’s book on life extension that is the first of its kind.

Death is Wrong - by Gennady Stolyarov II, Illustrated by Wendy Stolyarov

Death is Wrong – available in both paperback and Kindle editions – fills an important void. Virtually everyone learns about death as a child, and the initial reaction is the correct one: bewilderment, horror, and outrage. Yet there has been no resource to validate these completely correct first impressions. Almost immediately, the young ones are met with excuses and rationalizations, so that they might be consoled and return to a semblance of normalcy. Over millennia of facing indeed inevitable demises, humans have constructed elaborate edifices of rationalization, designed to keep thoughts of death from intruding upon their day-to-day lives. While understandable in eras when technological progress could not have been expected to attain radical life extension (see Benjamin Franklin’s famous lament that he was born too soon), today such evasions of the grave wrong of death are among the most counterproductive attitudes imaginable. Now that technological progress could bring us into the bright age of indefinite longevity within our lifetimes, every atavistic remnant of the old death acceptance poses a barrier that must be surmounted. The fewer barriers life-extension progress encounters, the faster indefinite lifespans will arrive for us; the more of us will be preserved from oblivion.

While transhumanists and life-extension advocates have made headway with conveying their aspirations for the future to some of the most technically educated and philosophically inclined adults, the mainstream of society remains pervaded by the old death-acceptance arguments – religious and secular: from the fear of “playing God” to the specter of overpopulation. Every mind held captive by these traditional and Malthusian pro-death prejudices is a mind that will at best not help life-extension progress and at worst hinder it greatly – a higher likelihood for the most intelligent purveyors of the death-acceptance mindset. People who embrace these notions and find them credible (despite the relative ease of debunking them using logic and evidence) largely do so because the fallacies were ingrained into them since childhood, with no counterarguments being presented or even posited as conceivable. So, if the antidote to these fallacies is to be most effective, it must be administered in childhood.

Death is Wrong will be easily understood by most eight-year-olds, though my aim is to encompass as young an audience as possible. The beautiful and detailed illustrations will help keep young minds engaged as they read about long-lived organisms found in nature, as well as the great advocates of life extension from the past and the present (featured in the book are Francis Bacon, Benjamin Franklin, Marquis de Condorcet, Friedrich Nietzsche, Alan Harrington, and Aubrey de Grey). The book discusses successes in animal life extension, along with providing a concise introduction to Dr. de Grey’s SENS program and the seven principal types of damage that must be addressed in order to reverse senescence. Parts of the book are autobiographical: they describe my own experiences as a child finding out about death and vowing to combat it. The book also focuses of refuting the common pro-death rationalizations and presenting young readers with all of the amazing opportunities and possibilities that can only exist if humans live much, much longer than is presently the case. At the end is a call to action and a list of further resources for young readers to find out more and to become involved with the life-extension movement.

Some may question my tactic of assailing death itself directly – an approach that strikes at the very attitudes enabling acceptance of the Dragon-Tyrant in the room (not the elephant, because elephants are largely innocuous). Yet this is not the time for prevarication or for dampening the rhetoric to the point where one only advocates greater “healthspans” or “compression of morbidity” or any incremental stopping place for progress. While the achievement of indefinite lifespans (and functional immortality, through improvements to the safety of humans’ environment and to the institutional incentives to avoid violence) will not come all at once, and incremental discoveries and lifespan extensions will certainly be the process leading to the goal, the goal itself – defeating death – should not be forgotten or dismissed. The grave wrong of death is worse than that of slavery – once a ubiquitous institution that every society took for granted. William Lloyd Garrison, the 19th-century abolitionist, recognized that the way to get slavery to disappear was to emphasize the feasibility and desirability of its complete eradication: “Urge immediate abolition as earnestly as we may, it will, alas! be gradual abolition in the end. We have never said that slavery would be overthrown by a single blow; that it ought to be, we shall always contend.” [1] Truer words were never spoken when it comes to the abolition of innocent human death. For those of us life-extension advocates who cannot participate in the research directly (other than donating money and other services to aid the researchers), the most promising path to follow is the example of William Lloyd Garrison. We should emphasize the urgency, the moral necessity, the undeniable justice of abolishing the death of innocent humans as soon as possible. We need to transform the culture so that it comes to reject death much as it was transformed to reject slavery after millennia of blithe acceptance. Then the research funding will flow, the votes and political rhetoric will follow, and even theologies and philosophies will be reinterpreted to view the fight against death on Earth to be the natural conclusion of every religious faith and secular ideology.

The spread of Death is Wrong to children is just one piece of the strategy of advocating for the abolition of the death of innocents. I would admire and embrace every activist project – including other children’s books – aimed toward this same cultural transformation. For those who have been wondering how they personally could contribute to the prospects of achieving indefinite longevity within our lifetimes, I hope that this book offers inspiration as well as some concrete possibilities for action. Even a single pro-longevity activist in a community could make a tremendous difference by donating copies of Death is Wrong to libraries, schools, bookstores, and children’s activity groups – or directly to children with whom the activist is acquainted.

Perhaps, if enough of today’s children read Death is Wrong, they would not view us life-extension advocates as hopeless oldsters lost in unattainable fantasy, thirty-two years into the future. Rather, they would be young alongside us, working to build a human civilization truly worthy of the name – one that is permeated by peace, prosperity, virtue, and a striving to ceaselessly progress as humankind comes to inhabit, develop, beautify, and ennoble the universe at large.

[1] Quoted in William H. Pease and Jane H. Pease, eds., The Antislavery Argument (Indianapolis: Bobbs-Merrill Co., 1965), p. xxxv.

“Death is Wrong”: Illustrated Children’s Book on Life Extension – Announcement and Short Excerpt – Video by G. Stolyarov II

“Death is Wrong”: Illustrated Children’s Book on Life Extension – Announcement and Short Excerpt – Video by G. Stolyarov II

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Death is Wrong is the ambitious new book for children and for life-extension advocates of all ages.

If you have ever asked, “Why do people have to die?” then this book is for you. The answer is that no, death is not necessary, inevitable, or good. In fact, death is wrong. Death is the enemy of us all, to be fought with medicine, science, and technology. This book introduces you to the greatest, most challenging, most revolutionary movement to radically extend human lifespans so that you might not have to die at all.

You will learn about some amazingly long-lived plants and animals, recent scientific discoveries that point the way toward lengthening lifespans in humans, and simple, powerful arguments that can overcome the common excuses for death. If you have ever thought that death is unjust and should be defeated, you are not alone. Read this book, and become part of the most important quest in human history.

This book was written by the philosopher and futurist Gennady Stolyarov II and illustrated by the artist Wendy Stolyarov. It is here to show you that, no matter who you are and what you can do, there is always a way for you to help in humanity’s struggle against death.

The First Edition of Death is Wrong was published by the Rational Argumentator Press.

References

– Paperback version on Amazon
– Kindle version on Amazon
– Paperback version on Createspace

Reviews

“Not too grammatically complex, and not too excruciatingly simplistic, Death is Wrong is a blunt dose of reality, quick to the punch and holding nothing back. This is the book I wish I’d have read as a young child.”

~ B. J. Murphy – The Proactionary Transhumanist. Read the full review.

“I thought the book was fun to read and important in what it tries to accomplish.”

~ Zoltan Istvan – Psychology Today. Read the full review.