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Criticizing Programmed Theories of Aging – Article by Reason

Criticizing Programmed Theories of Aging – Article by Reason

The New Renaissance HatReason
******************************

Today I’ll point out an open-access critique of programmed aging theories by the originator of the disposable soma theory of aging, one of the modern views of aging as accumulated damage rather than programming. The question of how and why we age is wrapped in a lot of competing theory, but of great practical importance. Our biochemistry is enormously complex and incompletely mapped, and thus the processes of aging, which is to how exactly our biochemistry changes over time, and all of the relationships that drive that change, are also enormously complex and incompletely mapped. Nonetheless, there are shortcuts that can be taken in the face of ignorance: the fundamental differences between young and old tissue are in fact well cataloged, and thus we can attempt to reverse aging by treating these changes as damage and repairing them. If you’ve read through the SENS rejuvenation research proposals, well, that is the list. The research community may not yet be able to explain and model how exactly this damage progresses, interacts, and spreads from moment to moment, but that effort isn’t necessary to build repair therapies capable of rejuvenation. You don’t need to build a full model of the way in which paint cracks and peels in order to scrub down and repaint a wall, and building that model is a lot most costly than just forging ahead with the painting equipment.

The engineering point of view described above, simply getting on with the job when there is a good expectation of success, is somewhat antithetical to the ethos and culture of the sciences, which instead guides researchers to the primary goal of obtaining full understanding of the systems they study. In practice, of course, every practical application of the life sciences is created in a state of partial ignorance, but the majority of research groups are nonetheless oriented towards improving the grand map of the biochemistry of metabolism and aging rather than doing what can be done today to create rejuvenation therapies. Knowledge over action. If we had all the time in the world this would be a fine and golden ideal. Unfortunately we do not, which places somewhat more weight on making material progress towards the effective treatment of aging as a medical condition – ideally by repairing its causes.

But what are the causes of aging? The majority view in the research community is that aging is a process of damage accumulation. The normal operation of metabolism produces forms of molecular damage in cells and tissues, a sort of biological wear and tear – though of course the concept of wear and tear is somewhat more nuanced and complex in a self-repairing system. This damage includes such things as resilient cross-links that alter the structural properties of the extracellular matrix and toxic metabolic waste that clutters and harms long-lived cells. As damage accumulates, our cells respond in ways that are a mix of helpful and harmful, secondary and later changes that grow into a long chain of consequences and a dysfunctional metabolism that is a long way removed from the well-cataloged fundamental differences between old and young tissues. An old body is a complicated mess of interacting downstream problems. In recent years, however, a growing minority have suggested and theorized that aging is not caused by damage, but is rather a programmed phenomenon – that some portion of the what I just described as the chain of consequences, in particular epigenetic changes, are in fact the root cause of aging. In the programmed view of aging, epigenetic change causes dysfunction and damage, not the other way around. That these two entirely opposite views can exist is only possible because there is no good map of the detailed progression of aging – only disconnected snapshots and puzzle pieces. There is a lot of room to arrange the pieces in any way that can’t be immediately refuted on the basis of well-known past studies.

There are two ways to settle the debate of aging as damage versus aging as evolved program. The first is to produce that grand map of metabolism and aging, something that I suspect is at the least decades and major advances in life science automation removed from where we stand now. The other is to build therapies that produce large degrees of rejuvenation, enough of a difference to put it far beyond argument that the approach taken is the right one. That is not so far away, I believe, as the first SENS rejuvenation therapies are presently in the early stages of commercial development. I think that, even with the comparative lack of funding for this line of development, ten to twenty years from now the question will be settled beyond reasonable doubt. Meanwhile, the programmed-aging faction has become large enough and their positions coherent enough that the mainstream is beginning to respond substantially to their positions; I expect that this sort of debate will continue all the way up to and well past the advent of the first meaningful rejuvenation therapies, which at this point look to be some form of senescent cell clearance.

Can aging be programmed? A critical literature review – by Axel Kowald and Thomas B. L. Kirkwood

Quote:

Many people, coming new to the question of why and how aging occurs, are attracted naturally to the idea of a genetic programme. Aging is necessary, it is suggested, either as a means to prevent overcrowding of the species’ environment or to promote evolutionary change by accelerating the turnover of generations. Instead of programmed aging, however, the explanation for why aging occurs is thought to be found among three ideas all based on the principle that within iteroparous species (those that reproduce repeatedly, as opposed to semelparous species, where reproduction occurs in a single bout soon followed by death), the force of natural selection declines throughout the adult lifespan. This decline occurs because at progressively older ages, the fraction of the total expected reproductive output that remains in future, on which selection can act to discriminate between fitter and less-fit genotypes, becomes progressively smaller. Natural selection generally favours the elimination of deleterious genes, but if its force is weakened by age, and because fresh mutations are continuously generated, a mutation-selection balance results. The antagonistic pleiotropy theory suggests that a gene that has a benefit early in life, but is detrimental at later stages of the lifespan, can overall have a net positive effect and will be actively selected. The disposable soma theory is concerned with optimizing the allocation of resources between maintenance on the one hand and other processes such as growth and reproduction on the other hand. An organism that invests a larger fraction of its energy budget in preventing accumulation of damage to its proteins, cells and organs will have a slower rate of aging, but it will also have fewer resources available for growth and reproduction, and vice versa. Mathematical models of this concept show that the optimal investment in maintenance (which maximizes fitness) is always below the fraction that is necessary to prevent aging.

In recent years, there have been a number of publications claiming that the aging process is a genetically programmed trait that has some form of benefit in its own right. If this view were correct, it would be possible experimentally to identify the responsible genes and inhibit or block their action. This idea is, however, diametrically opposed to the mainstream view that aging has no benefit by its own and is therefore not genetically programmed. Because experimental strategies to understand and manipulate the aging process are strongly influenced by which of the two opinions is correct, we have undertaken here a comprehensive analysis of the specific proposals of programmed aging. On the principle that any challenge to the current orthodoxy should be taken seriously, our intention has been to see just how far the various hypotheses could go in building a convincing case for programmed aging.

This debate is not only of theoretical interest but has practical implications for the types of experiments that are performed to examine the mechanistic basis of aging. If there is a genetic programme for aging, there would be genes with the specific function to impair the functioning of the organism, that is to make it old. Under those circumstances, experiments could be designed to identify and inhibit these genes, and hence to modify or even abolish the aging process. However, if aging is nonprogrammed, the situation would be different; the search for genes that actively cause aging would be a waste of effort and it would be too easy to misinterpret the changes in gene expression that occur with aging as primary drivers of the senescent phenotype rather than secondary responses (e.g. responses to molecular and cellular defects). It is evident, of course, that genes influence longevity, but the nature of the relevant genes will be very different according to whether aging is itself programmed or not.

For various programmed theories of aging, we re-implemented computational models, developed new computational models, and analysed mathematical equations. The results fall into three classes. Either the ideas did not work because they are mathematically or conceptually wrong, or programmed death did evolve in the models but only because it granted individuals the ability to move, or programmed death did evolve because it shortened the generation time and thus accelerated the spread of beneficial mutations. The last case is the most interesting, but it is, nevertheless, flawed. It only works if an unrealistically fast-changing environment or an unrealistically high number of beneficial mutations are assumed. Furthermore and most importantly, it only works for an asexual mode of reproduction. If sexual reproduction is introduced into the models, the idea that programmed aging speeds up the spread of advantageous mutations by shortening the generation time does not work at all. The reason is that sexual reproduction enables the generation of offspring that combine the nonaging genotype of one parent with the beneficial mutation(s) found in the other parent. The presence of such ‘cheater’ offspring does not allow the evolution of agents with programmed aging.

In summary, all of the studied proposals for the evolution of programmed aging are flawed. Indeed, an even stronger objection to the idea that aging is driven by a genetic programme is the empirical fact that among the many thousands of individual animals that have been subjected to mutational screens in the search for genes that confer increased lifespan, none has yet been found that abolishes aging altogether. If such aging genes existed as would be implied by programmed aging, they would be susceptible to inactivation by mutation. This strengthens the case to put the emphasis firmly on the logically valid explanations for the evolution of aging based on the declining force of natural selection with chronological age, as recognized more than 60 years ago. The three nonprogrammed theories that are based on this insight (mutation accumulation, antagonistic pleiotropy, and disposable soma) are not mutually exclusive. There is much yet to be understood about the details of why and how the diverse life histories of extant species have evolved, and there are plenty of theoretical and experimental challenges to be met. As we observed earlier, there is a natural attraction to the idea that aging is programmed, because developmental programming underpins so much else in life. Yet aging truly is different from development, even though developmental factors can influence the trajectory of events that play out during the aging process. To interpret the full complexity of the molecular regulation of aging via the nonprogrammed theories of its evolution may be difficult, but to do it using demonstrably flawed concepts of programmed aging will be impossible.

Given that the author here has in the past been among those who dismissed the SENS initiative as an approach to treating aging by repairing damage, it is perhaps a little amusing to see him putting forward points such as this one: “despite the cogent arguments that aging is not programmed, efforts continue to be made to establish the case for programmed aging, with apparent backing from quantitative models. It is important to take such claims seriously, because challenge to the existing orthodoxy is the path by which science often makes progress.” Where was this version of the fellow ten years ago?

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.
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This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.
An Interview with Kelsey Moody of Ichor Therapeutics, Bringing a SENS Therapy for Macular Degeneration to the Clinic – Article by Reason

An Interview with Kelsey Moody of Ichor Therapeutics, Bringing a SENS Therapy for Macular Degeneration to the Clinic – Article by Reason

The New Renaissance HatReason
******************************

As I mentioned last week, earlier this year Fight Aging! invested a modest amount in the Ichor Therapeutics initiative to develop a treatment for macular degeneration, joining a number of other amateur and professional investors in helping to get this venture started. The approach taken here is based on the results of research carried out at the Methuselah Foundation and SENS Research Foundation over much of the past decade, funded by philanthropists and the support of our community of longevity science enthusiasts. This is how we succeed in building the future: medical science in the laboratory leads to medical development in startup companies, each new stage bringing treatments capable of repairing specific forms of age-related molecular damage that much closer to the clinic.

Ichor Therapeutics is one of a growing number of success stories to emerge from the SENS rejuvenation research community. Young scientists, advocates, and donors involved in earlier projects – years ago now – have gone on to build their own ventures, while retaining an interest in stepping up to do something meaningful to help bring an end to aging. Back in 2010, Kelsey Moody worked on the LysoSENS project to find ways to break down damaging metabolic waste in old tissues; fast-forward six years, and he is the now the CEO of a successful small biotechnology company with a great team, taking that very same technology and putting it to good use. I recently had the chance to ask Kelsey a few questions about the future of SENS rejuvenation research, as well as how the Ichor scientists intend to construct a new class of therapy for macular degeneration, one based on removing one of the root causes of the condition.

Quote:

Who are the people behind Ichor Therapeutics? How did you meet and decide that this was the thing to do? Why macular degeneration as a target?

People have always been the focus of Ichor. Since day one we have worked to create a positive environment that cultivates a product-oriented research focus and emphasizes autonomy and personal accountability for work. As a result, ambitious self-starters tend to find their way to Ichor and remain here. However, we recognized early on that just filling a lab with a bunch of blue-eyed bushy tailed young up-and-comers is not sufficient to develop a robust, mature, translational pipeline. We have augmented our team with a number of critical staff members who are seasoned pharma operators, including our Quality Assurance Director and General Counsel.

Age-related macular degeneration (AMD) was chosen as a target because we believe it is the closest SENS therapy to the clinic. While we obviously have an interest in providing cures for the patients suffering from AMD and are attracted to the large market opportunities such a treatment could bring, our broader interest is in validating the entire SENS paradigm. We believe that Aubrey de Grey continues to receive excessive criticism because nothing spun out of SENS has ever made it into a legitimate pre-clinical pipeline, much less to the bedside. However, this does not mean he is wrong. Our goal is to be the first group to bring a SENS inspired therapy into the clinic and in doing so, silence critics and generate new energy and capital for this cause.

I understand there’s a lengthy origin story for the approach you are taking to treat AMD; it’d be great to hear some of it.

Our approach to treating AMD is based on the hypothesis that cellular junk that accumulates over the lifespan significantly contributes to the onset and progression of AMD. Our goal is to periodically reduce the burden of the junk so it never accumulates to levels sufficient to induce pathology. The strategy to accomplish this calls for the identification of enzymes that can break down the junk in a physiological setting, and the engineering of these enzymes such that they can break down the target in the correct organelle of the correct cell without appreciable collateral damage to healthy cells or tissue.

Methuselah Foundation and SENS Research Foundation did excellent work in establishing this program nearly a decade ago. They successfully identified a number of candidate enzymes that could break down the molecular junk, but reported that the targeting systems evaluated failed to deliver these enzymes to the appropriate organelles and cells. My group reevaluated these findings, and discovered that these findings were flawed. The delivery failure could be entirely attributed to a subtle, yet highly significant difference between how the target cells behave outside of the body as compared to inside the body. It turned out that the approach was in fact valid, it was the cell based assay that had been used that was flawed. This discovery was striking enough that SENS Research Foundation provided Ichor with funding and a material and technology transfer agreement to reassess the technology, and over $700,000 in directed program investments and grants have been received in the last year or two.

You recently completed a round of funding for the AMD work; what is the plan for the next year or so?

The new funds will allow us to develop a portfolio of enzyme therapy candidates to treat AMD. We will obtain critical data necessary to secure follow-on investment including in vitro studies (cell culture studies to confirm mechanism of action and cytotoxicity) and pivotal proof-of-concept in vivo studies, such as toxicity, PK/PD (how long the enzyme stays in the body and where), and efficacy. We will also be restructuring the company (reincorporating an IP holding company in Delaware, ensuring all contracts are up to date and audited) and ensuring our IP position is on solid footing (licensing in several related patents from existing collaborators, and filing several provisional patents from our intramural work). Collectively, we believe these efforts will position us to obtain series A for investigational new drug (IND) enabling pre-clinical studies.

You’ve been involved in the rejuvenation research community for quite some time now. What is your take on the bigger picture of SENS and the goal of ending aging?

This is a loaded question. What I can say is that the medical establishment has made great progress in the treatment of infectious disease through the development of antibiotics, vaccines, and hygiene programs. However, similar progress has not been realized for the diseases of old age, despite exorbitant expenditures. I have chosen to work in this space because I think a different approach is necessary, and it is here that I believe my companies and I can be the most impactful. I think SENS provides a good framework within which to ask and answer questions.

What do you see as the best approach to getting nascent SENS technologies like this one out of the laboratory and into the clinic?

We need more people who fully understand, in a highly detailed way, what a real translational path looks like. To take on projects like this, being a good scientist is not enough. We need people who can speak business, science, medicine, and legal, and apply these diverse disciplines to a well articulated, focused product or problem. There is no shortage of people who partially understand some of these, but the details are not somewhat important – they are all that matter for success in this space.

Another area is for investors. Some of the projects that come across my desk for review are truly abysmal, yet I have seen projects that are clearly elaborate hoaxes or outright scams (to anyone who has stepped foot in a laboratory) get funded to the tune of hundreds of thousands of dollars or more. While it is perfectly reasonable for high net worth individuals to gamble on moon shots in the anti-aging space (and I am ever grateful for the investors who have taken such a gamble on us) even aggressive development strategies should have some basis in reality. This is especially true as more and more high tech and internet investors move into the space.

If this works stupendously well, what comes next for Ichor Therapeutics?

I really want to get back into stem-cell research, but I basically need a blank check and a strong knowledge of the regulatory path to clinic before I feel comfortable moving into the space. A successful AMD exit would accomplish both of these goals, and position us to pivot to cell-based therapies.

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.
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This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.
Aubrey de Grey at the Launching Longevity Panel, and Announcing Acceptance of the First Paper to be Published on MitoSENS Research – Article by Reason

Aubrey de Grey at the Launching Longevity Panel, and Announcing Acceptance of the First Paper to be Published on MitoSENS Research – Article by Reason

The New Renaissance HatReason
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Today I’ll direct your attention to a couple of videos, thematically linked by the presence of Aubrey de Grey, cofounder of the SENS Research Foundation and tireless advocate for progress towards working rejuvenation therapies. For the first of the videos, de Grey recently took part in a panel discussion involving representatives of the biotechnology industry, the research establishment, and venture capital community, with the topic being the coming development of a new industry that will develop therapies to extend healthy life and turn back aging. That industry has barely started to form its earliest and smallest stage today, as the first lines of rejuvenation research reach the point of commercial viability. There are a few startups and a lot of deep pockets yet to be convinced that this is going somewhere – though the commentary in the panel is encouraged, considering those involved.

The recent Rejuvenation Biotechnology 2016 conference hosted by the SENS Research Foundation was more along the same lines, focused on creating a foundation for the near future industry that will build and provide rejuvenation therapies. The purpose of the conference series is to help smooth the way for these treatments to move rapidly from the laboratory to the clinic, to build the necessary relationships, manage expectations, and pull in the additional support needed to make best possible progress. The conference was livestreamed over the past couple of days, and at one point Aubrey de Grey announced the just-then-and-there acceptance of the first scientific publication for the MitoSENS team at the SENS Research Foundation. They are presently in the lead, at the cutting edge, among the few groups working on the project of copying mitochondrial genes into the cell nucleus to protect them from the damage of aging. Ultimately, copying all thirteen genes should completely remove the contribution of mitochondrial damage to degenerative aging, as mitochondria will no longer become dysfunctional as their local DNA is damaged. They will get the proteins they need from the cell nucleus instead. It is a worthy project, and it is always welcome to see progress on this front.

Launching Longevity: Funding the Fountain of Youth

 

Can technology make human longevity a reality? As the pace of discovery accelerates, scientists and entrepreneurs are closing in on the Fountain of Youth. Disrupting the aging process by hacking the code of life, promises better health and longer maximum lifespans. With many layers of complexity from science to ethics, there are still skeptics placing odds against human longevity. Venture capitalists are betting on success; putting big money on the table to fund longevity startups. Google/Alphabet and drugmaker AbbVie have invested $1.5 billion on Calico, while Human Longevity Inc. recently raised $220 million from their Series B funding round. Complementing traditional venture investment, VCs like Peter Thiel and Joon Yun have established foundations and prizes to accelerate the end of aging. Why are VCs suddenly investing heavily in longevity startups? Will extended lifespan be a privilege of the wealthy or will the benefits be accessible to all? How long before these well-funded startups bring viable products to market?

 

Aubrey de Grey Announces Progress in MitoSENS

 

Ok everybody, before I introduce the next session I just wanted to make a very small, brief, but very welcome announcement. Literally half an hour ago we received some extremely good scientific news. Those of you who have been following SENS research since before the SENS Research Foundation itself even existed will know that, about a decade ago, the very first project, the very first research program that we were able to initiate – with the help of, especially, the initial donation of Peter Thiel – was to make mitochondrial mutations harmless by essentially putting backup copies of the mitochondrial DNA into the nuclear genome, modified in such way of course that the encoded proteins would be colocated back into the mitochondria to do their job. This is an idea that was first put forward more than 30 years ago, but it is an idea that despite quite a bit of initial effort, nobody was able to make work. When I first came across this concept, in fact I’d thought of it myself, it’s a pretty obvious idea really, I came to the conclusion that a lot of the despair and despondency and pessimism about this approach was premature, and that it was worth having another go, and so that was the very first project we decided to fund.

Suffice to say that it has not been quite as easy as I was hoping to make progress in that space, but progress has now been made, step by step, over the past several years, with the help especially of the absolutely amazing team we have at the research center, who work on this, headed by Matthew O’Connor. Amutha Boominathan is the number two on the team, and is absolutely indispensable, I’ve no idea where we’d be without her. So, what’s happened half an hour ago is that for the very first time in the entire history of this project, we have got far enough to have a paper accepted in a very nice journal, Nucleic Acids Research, which reports on our progress in this area. The headline result in this paper is that we are the first team ever to get two of the proteins encoded by genes in the mitochondrial DNA simultaneously functioning in the same cell line, and of course – two is equivalent to infinity for mathematicians, you know that, right? – this is extremely heartening news, and I just wanted to let you all know, thank you.

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.
Public Opposition to Biotech Endangers Your Life and Health – Article by Edward Hudgins

Public Opposition to Biotech Endangers Your Life and Health – Article by Edward Hudgins

The New Renaissance HatEdward Hudgins
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Do you want to be smarter, healthier, and live longer? Remarkably, a new Pew survey found that most Americans answer “No!” if it requires using certain new technologies. This is a wakeup call for scientists, Silicon Valley entrepreneurs, transhumanists, and all of us who value our lives: we must fight for our lives on the battlefield of values.

CRISPRWorries about human enhancement

We all understand how information technology has transformed our world with PCs, smartphones, the Internet, and Google. Nanotech, robotics, artificial intelligence, and, especially, genetic engineering are poised to unleash the next wave of wealth creation and improvements of the human condition.

But a new Pew survey entitled U.S. Public Wary of Biomedical Technologies to “Enhance” Human Abilities found that “Majorities of U.S. adults say they would be ‘very’ or ‘somewhat’ worried about gene editing (68%), brain chips (69%) and synthetic blood (63%),” technologies that in years to come could make us healthier, smarter, and stronger. While some say they “would be both enthusiastic and worried … overall, concern outpaces excitement.” Further, “More say they would not want enhancements of their brains and their blood (66% and 63%, respectively) than say they would want them (32% and 35%).”

Simply a reflection of individuals making decisions about their own lives, as is their right? Not quite. Their concerns about technology are already causing cultural and political pushback from left and right that could derail the advances sought by those of us who want better lives.

The Pew data reveals two ideological sources of opposition to new technologies.

Religion and meddling with nature

brain.chip_.grids_The survey found that 64% of Americans with a high religious commitment say “gene editing giving babies a much reduced disease risk” is “meddling with nature and crosses a line we should not cross.” Are you stunned that anyone could prefer to expose their own babies to debilitating or killer diseases when a prevention is possible?

And 65% with such a commitment have a similar opinion of “brain chip implants for much improved cognitive abilities.” Better to remain ignorant when a way to more knowledge is possible?

Obsession with inequality of abilities

When asked if “gene editing giving babies a much reduced disease risk” is an appropriate use of technology, 54% answered “Yes” if it results in people “always equally healthy as the average person.” But only 42% approved if it results in people “far healthier than any human known to date.” Similarly, 47% approved of synthetic blood if it results in physical improvements in individuals “equal to their own peak ability,” while only 28% approved if it results in improvements “far above that of any human known to date.”

Here we see the ugly side of egalitarianism. Better for everyone to be less healthy than for some to be healthier than others.

synthetic_blood-alamy_SmallThis inequality concern is another aspect of warped values we find in economic discussions. What if everyone enjoys rising levels of prosperity in a free-market system, but some individuals—Steve Jobs? Mark Zuckerberg?—become much wealthier than others through their own productive efforts? It’s win-win! But many would punish and demonize such achievers because they are the “top 1 percent,” even if such treatment means that those achievers produce less and, thus, everyone is less prosperous. Better we’re all poorer but more equal.

A disappearing digital divide

We saw this inequality concern in the 1990s when desktop PCs and the Internet were taking off. Some projected a “digital divide.” There would be more intelligent and advantaged individuals because they could access a universe of information through these technologies. And there would be those with little access who would fall further behind. Of course, what fell was the price of those technologies, which even then were accessible for free at most local libraries and now are in laptops, tablets, and smartphones, and affordable to most low-income individuals. The divide disappeared.

 Computers

There were early adopters prosperous enough to try new information technologies. Similarly, there will be early adopters of biomedical tech, which later will become accessible to all—but only if enough people value it rather than fear it and demand that the government stop it.

The fight for values

In a companion piece to the Pew survey, entitled Human Enhancement: The Scientific and Ethical Dimensions of Striving for Perfection, Pew senior writer David Masci offers a good overview of serious moral issues raised by biotech and other exponential technologies. And those of us who welcome these technologies must fight for the moral values on which they are based.

We truly value our lives, and the happiness and flourishing that we as individuals can get out of them through our own achievements. We must shake others out of their spiritual lethargy so that they too will not let their precious lives waste away.

We must promote the values of reason and science as the means to better technology and as guides for our individual lives. Misguided dogmas, whether religious or political, lead to social and personal stagnation.

We must develop and implement strategies to promote human achievement, including enhancement of our capacities, as a value in our culture through our institutions—schools, media—and our aesthetics—movies, art, music.

We must offer an exciting and compelling vision of a fantastic, nonfiction future, of a world as it can be and should be, especially to young people who thirst for a future that will be worth living.

The values on which this future is based will not sell themselves. We must not only create the technology that will allow us to live healthier, smarter and stronger. We must also create the culture that will encourage and celebrate the creation and use of such technology.

Edward Hudgins is the director of advocacy for The Atlas Society and the editor and author of several books on politics and government policy.

Copyright The Atlas Society. For more information, please visit www.atlassociety.org.

Towards a Greater Knowledge of Mitochondrial DNA Damage in Aging – Article by Reason

Towards a Greater Knowledge of Mitochondrial DNA Damage in Aging – Article by Reason

The New Renaissance HatReason
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Today I’ll point out a very readable scientific commentary on mutations in mitochondrial DNA (mtDNA) and the importance of understanding how these mutations spread within cells. This is a topic of some interest within the field of aging research, as mitochondrial damage and loss of function is very clearly important in the aging process. Mitochondria are, among many other things, the power plants of the cell. They are the evolved descendants of symbiotic bacteria, now fully integrated into our biology, and their primary function is to produce chemical energy store molecules, adenosine triphosphate (ATP), that are used to power cellular operations. Hundreds of mitochondria swarm in every cell, destroyed by quality control processes when damaged, and dividing to make up the numbers. They also tend to promiscuously swap component parts among one another, and sometimes fuse together.

Being the descendants of bacteria, mitochondria have their own DNA, distinct from the nuclear DNA that resides in the cell nucleus. This is a tiny remnant of the original, but a very important remnant, as it encodes a number of proteins that are necessary for the correct operation of the primary method of generating ATP. DNA in cells is constantly damaged by haphazard chemical reactions, and equally it is constantly repaired by a range of very efficient mechanisms. Unfortunately mitochondrial DNA isn’t as robustly defended as nuclear DNA. Equally unfortunately, some forms of mutation, such as deletions, seem able to rapidly spread throughout the mitochondrial population of a single cell, even as they make mitochondria malfunction. This means that over time a growing number of cells become overtaken by malfunctioning mitochondria and fall into a state of dysfunction in which they pollute surrounding tissues with reactive molecules. This can, for example, increase the level of oxidized lipids present in the bloodstream, which speeds up the development of atherosclerosis, a leading cause of death at the present time.

The question of how exactly some specific mutations overtake a mitochondrial population so rapidly is still an open one. There is no shortage of sensible theories, for example that it allows mitochondria to replicate more rapidly, or gives them some greater resistance to the processes of quality control that normally cull older, damaged mitochondria. The definitive proof for any one theory has yet to be established, however. In one sense it doesn’t actually matter all that much: there are ways to address this problem through medical technology that don’t require any understanding of how the damage spreads. The SENS Research Foundation, for example, advocates the path of copying mitochondrial genes into the cell nucleus, a gene therapy known as allotopic expression. For so long as the backup genes are generating proteins, and those proteins make it back to the mitochondria, the state of the DNA inside mitochondria doesn’t matter all that much. Everything should still work, and the present contribution of mitochondrial DNA damage to aging and age-related disease would be eliminated. At the present time there are thirteen genes to copy, a couple of which are in commercial development for therapies unrelated to aging, another couple were just this year demonstrated in the lab, and the rest are yet to be done.

Still, the commentary linked below is most interesting if you’d like to know more about the questions surrounding the issue of mitochondrial DNA damage and how it spreads. This is, as noted, a core issue in the aging process. The authors report on recent research on deletion mutations that might sway the debate on how these mutations overtake mitochondrial populations so effectively.

Expanding Our Understanding of mtDNA Deletions

A challenge of mtDNA genetics is the multi-copy nature of the mitochondrial genome in individual cells, such that both normal and mutant mtDNA molecules, including selfish genomes with no advantage for cellular fitness, coexist in a state known as “heteroplasmy.” mtDNA deletions are functionally recessive; high levels of heteroplasmy (more than 60%) are required before a biochemical phenotype appears. In human tissues, we also see a mosaic of cells with respiratory chain deficiency related to different levels of mtDNA deletion. Interestingly, cells with high levels of mtDNA deletions in muscle biopsies show evidence of mitochondrial proliferation, a compensatory mechanism likely triggered by mitochondrial dysfunction. In such circumstances, deleted mtDNA molecules in a given cell will have originated clonally from a single mutant genome. This process is therefore termed “clonal expansion.”

The accumulation of high levels of mtDNA deletions is challenging to explain, especially given that mitophagy should provide quality control to eliminate dysfunctional mitochondria. Studies in human tissues do not allow experimental manipulation, but large-scale mtDNA deletion models in C. elegans have proved to be helpful, showing some conserved characteristics that match the situation in humans, as well as some divergences. Researchers have used a C. elegans strain with a heteroplasmic mtDNA deletion to demonstrate the importance of the mitochondrial unfolded protein response (UPRmt) in allowing clonal expansion of mutant mtDNAs to high heteroplasmy levels. They demonstrate that wild-type mtDNA copy number is tightly regulated, and that the mutant mtDNA molecules hijack endogenous pathways to drive their own replication.

The data suggests that the expansion of mtDNA deletions involves nuclear signaling to upregulate the UPRmt and increase total mtDNA copy number. The nature of the mito-nuclear signal in this C. elegans model may have been the transcription factor ATFS-1 (activating transcription factor associated with stress-1), which fails to be imported by depolarized mitochondria, mediates UPRmt activation by mtDNA deletions. A long-standing hypothesis proposes that deleted mtDNA molecules clonally expand because they replicate more rapidly due to their smaller size. To address this question, researchers examined the behavior of a second, much smaller mtDNA deletion molecule. They found no evidence for a replicative advantage of the smaller genome, and clonal expansion to similar levels as the larger deletion. In human skeletal muscle, mtDNA deletions of different sizes also undergo clonal expansion to the same degree. Furthermore, point mutations that do not change the size of the total mtDNA molecule also successfully expand to deleterious levels, indicating that clonal expansion is not driven by genome size. Thus, similar mechanisms may be operating across organisms. In the worm, this involves mito-nuclear signaling and activation of the UPRmt.

There is some debate over interpretation of results. One paper indicates that UPRmt allows the mutant mtDNA molecules to accumulate by reducing mitophagy. Another demonstrates that the UPRmt induces mitochondrial biogenesis and promotes organelle dynamics (fission and fusion). Both papers show that by downregulating the UPRmt response, mtDNA deletion levels fall, which may allow a therapeutic approach in humans. Could there be a similar mechanism in humans, especially since some features detected in C. elegans are also present in human tissues, including the increase in mitochondrial biogenesis and the lack of relationship between mitochondrial genome size and expansion? It is likely that there will be a similar mechanism to preserve deletions since, as in the worm, deletions persist and accumulate in human tissues, despite an active autophagic quality-control process. Although the UPRmt has not been characterized in humans as it has in the worm, and no equivalent protein to ATFS-1 has been identified in mammals, proteins such as CHOP, HSP-60, ClpP, and mtHSP70 appear to serve similar functions in mammals as those in C. elegans and suggest that a similar mechanism may be present.

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.
Apollo 11 on Human Achievement Day – Article by Edward Hudgins

Apollo 11 on Human Achievement Day – Article by Edward Hudgins

The New Renaissance HatEdward Hudgins
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There are holidays and days of commemoration stretching from New Year’s to Independence Day to Christmas. A new one should be added to the calendar – informally rather than by government decree: Human Achievement Day — July 20th, the date in 1969 when human beings first landed on the Moon.

The most obvious benefit of living in society with others is that we can each specialize in the production of goods and services at which we are best and then trade with others, making us all prosperous. But in society we also have the opportunity to witness the achievements of others, which are constant reminders just how wonderful life can be. And among the greatest achievements in history, individuals using the three pounds of gray matter we each have in our heads figured out how to go to the Moon.

Think of the millions of parts and components and the engineering skills needed to make them function together in the Saturn V rocket, the Columbia Command module and the Eagle lunar lander that carried Neil Armstrong and Buzz Aldrin to the surface of another world. Think of the applications of old knowledge and the discovery of new knowledge needed to create those incredible systems.

Novelist-philosopher Ayn Rand understood the full moral meaning of these efforts when she wrote, “Think of what was required to achieve that mission: think of the unpitying effort; the merciless discipline; the courage; the responsibility of relying on one’s judgment; the days, nights and years of unswerving dedication to a goal; the tension of the unbroken maintenance of a full, clear mental focus; and the honesty.” It took the highest, sustained acts of virtue to create in reality what had only been dreamt of for millennia.

Ayn Rand‘s take on the landing was particularly instructive because of her novelist’s understanding of art, which, at its best, is a selective recreation of reality in light of the artist’s values. Thus Michelangelo’s David and Beethoven’s 9th portray humans as heroes. We go to art for emotional fuel and for the vision of the world as it can be and should be. In Apollo 11 she saw such a vision made manifest.

Concerning the pure exaltation from watching the launch from the Kennedy Space Center, Ayn Rand said that, “What we had seen in naked essentials – but in reality, not in a work of art – was the concretized abstraction of man’s greatness.” The mission “conveyed the sense that we were watching a magnificent work of art – a play dramatizing a single theme: the efficacy of man’s mind.” And “The most inspiring aspect of Apollo 11’s flight was that it made such abstractions as rationality, knowledge, science perceivable in direct, immediate experience. That it involved a landing on another celestial body was like a dramatist’s emphasis on the dimensions of reason’s power.”

Of course the Moon landings were government-funded; if the private sector had led the way we still probably would have traveled to the Moon, only some years later. Today it is private entrepreneurs — the kind who have given us the personal computers, Internet and information revolution — who are turning their creativity to the final frontier. Burt Rutan, who won the private X-Prize by placing a man into space twice in a two-week period on the private, reusable SpaceShipOne, follows in the spirit of Apollo. The celebration of those flights in late 2004 showed how healthy human beings relish the display of efficacious minds.

So on July 20th let’s each reflect on our achievements — as individuals and as we work in concert with others. Let’s recognize that achievements of all sorts — epitomized by the Moon landings — are the essence and the expected of human life. Let’s rejoice on this day and commemorate the best within us with, as Ayn Rand would say, the total passion for the total heights!

Edward Hudgins is the director of advocacy for The Atlas Society and the editor and author of several books on politics and government policy.

Copyright The Atlas Society. For more information, please visit www.atlassociety.org.

It’s Time to Postpone Your Appointment with the Grim Reaper – Article by Gerrard Jayaratnam

It’s Time to Postpone Your Appointment with the Grim Reaper – Article by Gerrard Jayaratnam

The New Renaissance HatGerrard Jayaratnam
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How long would you like to live for? Is there a limit to how long we can live for? These are not questions you hear often, but do not be surprised if they are repeated more frequently in the future. The reason? Life extension. It is the concept of living well beyond the average lifespan. [1]

Humans are already living longer due to vaccines and improvements in sanitation. [2] The World Health Organization reported that the average life expectancy at birth increased from 48 years in 1955 to 65 years in 1995, and is projected to rise to 73 years by 2025. [3] As medical techniques continue to improve, we are more inclined than ever to pursue life extension. [1] Indeed, from the Epic of Gilgamesh to China’s First Emperor, prolonging life has been an ever-present thought in society. [4, 5] Both individuals failed to escape death, but the idea of life extension ironically lives on. Even so, is it truly possible and what should upcoming doctors and scientists consider if they are to join the most ambitious of quests?

The “Horcruxes” of reality 

In the fictional Harry Potter series, “Horcruxes” were objects where people could hide a fragment of their soul in an attempt to take one step towards immortality. [6] Of course, humans cannot split their souls and hide them in objects, but there are several proposed means by which life extension may be achieved. [1] This is a testimony to the progress within the life extension field, but there remains much room for improvement.

Eat less, live more

Caloric restriction (CR) is one proposed method for life extension. [1] In the CALERIE (Comprehensive Assessment of Long term Effects of Reducing Intake of Energy) trial, 218 non-obese humans were randomised to either a control group or an intervention group. The latter aimed for a 25% reduction from baseline energy intake. At the end of the 2-year study period, the intervention group had significantly greater reductions in circulating levels of TNF-α – an inflammatory marker involved in many age-related diseases. [7] Dr Alexander Miras, winner of the 2014 Nutrition Society Cuthbertson Medal for his research on bariatric surgery, acknowledges that the study was a “good first step,” but argues that “the evidence in humans is lacking.” “A definitive RCT (randomised controlled trial),” Dr Miras continues, “would be very hard, if not impossible.” He also spots a glaring consequence of CR. “My personal approach is to avoid caloric restriction as this leads to hunger which is an unpleasant feeling. I would rather live a shorter life, but enjoy my food.”

Manipulating telomerase

One alternative is modulating telomerase activity – as attempted with the anti-ageing TA-65MD® supplement. [8] Telomeres protect the ends of chromosomes [9]; they resemble the aglets on the ends of shoelaces. Just as shoelaces would unravel without the aglet, chromosomes would lose vital DNA sequences in the absence of telomeres. [9] Our cells divide over time, causing telomeres to shorten. Once the telomere becomes too short, cell division ceases, and short telomeres correlate with cellular ageing. [10] Telomerase is an enzyme that can oppose telomere shortening [10] – it was what Hamlet was to King Claudius; what exercise is to obesity; and what junior doctors, in England, will be to Jeremy Hunt.

Reactivating telomerase in telomerase-deficient mice reversed both neurodegeneration and degeneration of other organs. [11] This proved the concept that boosting telomerase activity could have anti-ageing effects, but there is little proof that this occurs in humans. While the mice were telomerase-deficient, humans normally have some telomerase activity. It is like giving food to someone who has been fasting for hours and to someone who has just eaten a three-course meal – the starved individual would unquestionably benefit more. A 12-month long RCT, involving 117 relatively healthy individuals (age range: 53-87), found that low-dose TA-65 significantly increased telomere length when compared to placebo. High-dose TA-65, however, failed to do so. [12]

Dancing with the devil

What is more worrying than treatments that may be ineffective? Side effects. Telomerase is a double-edged sword and by reducing telomere attrition, it can promote unlimited cell division and cancer. [9] Elizabeth Blackburn, co-winner of the 2009 Nobel Prize in Physiology or Medicine for her role in the discovery of telomerase, has doubts about exploiting the enzyme. Speaking to TIME magazine, she said, “Cancers love telomerase, and a number of cancers up-regulate it like crazy. . . . My feeling would be that if I take anything that would push my telomerase up, I’m playing with fire.” [13]

A cauldron of rewards

CR and boosting telomerase activity are just a small sample of life extending techniques, yet there is the notion that such techniques will be intertwined with risks. However, risks are always weighed against rewards, and Gennady Stolyarov, editor-in-chief of The Rational Argumentator and Chief Executive of the Nevada Transhumanist Party, believes life extension would bring “immense and multifaceted” rewards. “The greatest benefit is the continued existence of the individual who remains alive. Each individual has incalculable moral value and is a universe of ideas, experiences, emotions, and memories. When a person dies, that entire universe is extinguished . . . This is the greatest possible loss, and should be averted if at all possible.” Stolyarov also envisages “major savings to healthcare systems” and that “the achievement of significant life extension would inspire many intelligent people to try to solve other age-old problems.”

Former chairman of the President’s Council on Bioethics, Leon Kass, disagrees with this view and argues that mortality is necessary for “treasuring and appreciating all that life brings.” [14] Hence, increased longevity could lead to an overall reduction in productivity over one’s lifetime. Perhaps Kass is correct, but the array of potential benefits makes it seem unwise to prematurely dismiss life extension. In fact, a survey, which examined the opinions of 605 Australians on life extension, highlighted further benefits – 23% of participants said they could “spend more time with family” and 4% cited the opportunity to experience future societies. [15]

Learning from our mistakes

Conversely, life extension may result in people enduring poor health for longer periods. 28% of participants in the Australian survey highlighted this concern. [15] Current trends in life expectancy reinforce their fears. Professor Janet Lord, director of the Institute of Inflammation and Ageing at the University of Birmingham, explains, “Currently, in most countries in the developed world, life expectancy is increasing at approximately 2 years per decade, but healthspan (the years spent in good health) is only increasing at 1.7 years. This has major consequences . . . as more of later life is spent in poor health.” This is a consequence of treating “killer diseases” – according to Dr Felipe Sierra, director of the Division of Aging Biology at the National Institute on Aging. “The current model in biomedicine,” says Dr Sierra, “is to treat one disease at a time. Let’s imagine you have arthritis; cancer; and are starting to develop Alzheimer’s disease. So what do we do? We treat you for cancer. You now live longer with Alzheimer’s disease and arthritis.” A better approach is clear to Dr Sierra who stresses the importance of compression of morbidity – “the goal is to live longer with less time spent being sick.”

Learning from our successes

Even with Dr Sierra’s approach, individual boredom and social implications, including overpopulation, would still be problems.[16] According to Stolyarov, the boredom argument does not hold up when facing “human creativity and discovery.” He believes humans could never truly be bored as “the number of possible pursuits increases far faster than the ability of any individual to pursue.”

In his novel Death is Wrong, Stolyarov explained that the idea that society could not cope with a rapidly expanding population was historically inaccurate. The current population “is the highest it has ever been, and most people live far longer, healthier, prosperous lives than their ancestors did when the Earth’s population was hundreds of times smaller.” [16] If it has been achieved in the past, who is to say our own society – one far more advanced than any before it – cannot adapt?

The verdict

Life extension research is quietly progressing, and there is a good chance that it will eventually come to fruition. Although there are doubts about current techniques, Dr Sierra draws attention to novel interventions, such as rapamycin, which “delay ageing in mice.” He concludes that the next challenge is to “develop measures than can predict whether an intervention works in a short-term assay.” Such measures would provide the scaffolding for future clinical trials that test life extension techniques.

Given what may be gained, it is no surprise that artificially prolonging life is exciting some in the same way the Tree of Knowledge tempted Eve. The impact on society? Impossible to predict. It would undoubtedly be a big risk, but perhaps in this complex and uncertain scenario, we ought to remember the words of the poet Thomas Stearns Eliot: “Only those who will risk going too far can possibly find out how far one can go.” [17]

Gerrard Jayaratnam is a student of Biomedical Science at Imperial College London.

References

  1. Stambler I. A History of Life-Extensionism in the Twentieth Century. Ramat Gan: CreateSpace Independent Publishing Platform; 2014.
  2. National Institute on Aging. Living Longer. 2011. https://www.nia.nih.gov/research/publication/global-health-and-aging/living-longer.
  3. World Health Organization. 50 Facts: Global Health situation and trends 1955-2025. 2013. http://www.who.int/whr/1998/media_centre/50facts/en/.
  4. Encyclopaedia Britannica. Epic of Gilgamesh. 2016. http://www.britannica.com/topic/Epic-of-Gilgamesh.
  5. Lloyd DF. The Man Who Would Cheat Death and Rule the Universe. Vision. 2008. http://www.vision.org/visionmedia/history-shi-huang-emperor-china/5818.aspx.
  6. Rowling JK. Harry Potter and the Half-Blood Prince. London: Bloomsbury Publishing; 2005.
  7. Ravussin E, Redman LM, Rochon J, et al. A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity. J Gerontol A Biol Sci Med Sci 2015;70:1097-1104.
  8. A. Sciences. What is TA-65®? (n.d.) [Accessed 3rd April 2016]. https://www.tasciences.com/what-is-ta-65/.
  9. De Jesus BB, Blasco MA. Telomerase at the intersection of cancer and aging. Trends Genet 2013;29:513-520.
  10. A. Sciences. Telomeres and Cellular Aging. (n.d.) [Accessed 3rd April 2016]. https://www.tasciences.com/telomeres-and-cellular-aging/.
  11. Jaskelioff M, Muller FL, Paik JH, et al. Telomerase reactivation reverses tissue degeneration in aged telomerase deficient mice. Nature 2011;469:102-106.
  12. Salvador L, Singaravelu G, Harley CB, et al. A Natural Product Telomerase Activator Lengthens Telomeres in Humans: A Randomized, Double Blind, and Placebo Controlled Study. Rejuvenation Res 2016; ahead of print. doi:10.1089/rej.2015.1793.
  13. Kluger J. The antiaging power of a positive attitude. TIME. 2015.
  14. Than K. The Psychological Strain of Living Forever. Live Science. 2006. http://www.livescience.com/10469-psychological-strain-living.html.
  15. Partridge B, Lucke J, Bartlett H, et al. Ethical, social, and personal implications of extended human lifespan identified by members of the public. Rejuvenation Res 2009;12:351-357.
  16. Stolyarov II G. Death is Wrong. 2nd ed. Carson City, Nevada: Rational Argumentator Press; 2013.
  17. The Huffington Post. 11 Beautiful T.S. Eliot Quotes. 2013. http://www.huffingtonpost.com/2013/09/26/ts-eliot-quotes_n_3996010.html.
Crowdfunding Longevity Science: An Interview with Keith Comito of Lifespan.io – Article by Reason

Crowdfunding Longevity Science: An Interview with Keith Comito of Lifespan.io – Article by Reason

The New Renaissance HatReason
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Keith Comito leads the volunteers of the non-profit Life Extension Advocacy Foundation (LEAF) and the crowdfunding initiative Lifespan.io, a site I’m sure you’ve seen at least in passing by now. The LEAF crew have put in a lot of effort to help make fundraisers for rejuvenation research projects a success both last year and this year. Two such crowdfunding campaigns are running right now, firstly senolytic drug research at the Major Mouse Testing Program with just a few days left to go, and in its stretch goals, and secondly the recently launched drug discovery for ALT cancers at the SENS Research Foundation. Both tie in to the SENS portfolio of research programs aimed at effective treatment of aging and all age-related conditions. These are large projects when taken as a whole, but the way forward in this as in all things is to pick out smaller, achievable goals, and set out to get them done. Then repeat as necessary.

I recently had the chance to ask Keith Comito a few questions about Lifespan.io, the state of funding for the interesting end of longevity science, and what he envisages for the years ahead. This is an interesting, revolutionary time for the life sciences, in which progress in biotechnology has made early stage research very cheap. A great deal can be accomplished at the cutting edge of medical science given access to an established lab, administrators who can break out small initiatives from the larger goals, smart young researchers, and a few tens of thousands of dollars. It is an age in which we can all help to advance the research we care about, by collaborating and donating, and it has never been easier to just reach out and talk to the scientists involved. If you haven’t taken a look at Lifespan.io and donated to one of the projects there, then you really should. This is a way to move the needle on aging research, and advance that much closer to effective treatments for the causes of aging.

Quote:

What is the Lifespan.io story in brief? What was the spur that made you come together and decide to do your part in the fight against aging?

Lifespan.io began to take shape at the tail end of 2012, as a result of a loose discussion group based in New York which consisted of citizen scientists such as myself and Dr. Oliver Medvedik, supporters of SENS, as well as a few healthcare practitioners. We began having monthly meetings to discuss what could be done to accelerate longevity research (usually in oddball locations like salad bars or subterranean Japanese restaurants befitting our motley crew) and eventually hit upon the idea of crowdfunding. What drew us to this idea was that it was something tangible: a concrete way to move the needle on important research not only through funds, but through raised awareness. It is fine to talk and rabble-rouse about longevity, but we felt such efforts would be much more effective if they were paired with a clear and consistent call to action – a path to walk the walk, so to speak. As this idea coalesced we formed the nonprofit LEAF to support this initiative, and the rest is history. Not every one from the initial discussions in 2012 remained throughout the intervening years, but we are thankful to all who gave us ideas in those early days of the movement.

I’d like to hear your take on why we have to advocate and raise funds at all – why the whole world isn’t rising up in support of treatments for the causes of aging.

The reasons why people and society at large have not prioritized anti-aging research thus far are myriad: fear of radical change, a history of failed attempts making it seem like a fools errand, long timescales making it a difficult issue for election-focused politicians to support, etc. The reason I find most personally interesting relates to cognitive bias – specifically the fact that our built-in mental hardware is ill-equipped to handle questions like “do you want to live 100 more years?” If instead you ask the questions “Do you want to be alive tomorrow?” and “Given that your health and that of your loved ones remains the same, do you suspect your answer to the first question will change tomorrow?”, the answers tend to be more positive.

This leads me to conclude that the state of affairs is not necessarily as depressing for our cause as it might appear, and that reframing the issue of healthy life extension in a way that will inspire and unite the broader populace is possible. Aubrey de Grey has spoken about “Longevity Escape Velocity” in relation to the bootstrapping of biomedical research, but I think the same idea applies to the public perception of life extension as well. The sooner we can galvanize the public to support therapies that yield positive results the easier it will become to invite others to join in this great work. It is all about jump starting the positive feedback loop, and that is why we believe rallying the crowd behind critical research and trumpeting these successes publicly is so vitally important.

What the future plans for Lifespan.io and the Life Extension Advocacy Foundation?

In addition to scaling up our ability to run successful campaigns on Lifespan.io, we look forward to improving our infrastructure at LEAF by bringing on some staff members to join the team. LEAF has largely been a volunteer effort thus far, and having the support of a staff will allow us to take on more campaigns as well as further improve the workflow to create and promote them. This will also free me up personally to more actively pursue potential grand slams for the movement, such as collaborations with prominent YouTube science channels to engage the public and policy related goals like the inclusion of a more useful classification of aging in the ICD-11.

Do you have any favored areas in research at the moment? Is there any particular field for which you’d like to see researchers approaching you for collaboration?

Senolytics is certainly an exciting area of research right now (congratulations Major Mouse Testing Program!), and a combination of successful senolytics with stem cell therapies could be a potential game changer. That being said I’d also like to see projects which address the truly core mechanics of aging, such as how damage is aggregated during stem cell division, and the potential differences in this process between somatic and germ cells. How can the germ line renew itself for essentially infinity? The real mystery here is not that we grow old, but how we are born young.

A related question: where do you see aging and longevity research going over the next few years?

In the near future we will likely continue to see the pursuit of compounds which restore bodily systems failing with age to a more youthful state. This will include validating in higher organisms molecules that have shown this sort of promise: rapamycin, metformin, IL-33 for Alzheimer’s, etc. This approach may sound incremental, but it actually signals a great paradigm shift from the old system of mostly ineffective “preventative measures” such as antioxidants. Things like nicotinamide mononucleotide (NMN), IL-33 – if successful these types of therapies can be applied when you are old, and help restore your bodily systems to youthful levels. That would be a pretty big deal.

Funding is ever the battle in the sciences, and especially for aging. Obviously you have strong opinions on this topic. How can we change this situation for the better?

I believe the key to greater funding, both from public and private sources, is to build up an authentic and powerful grassroots movement in support of healthy life extension. Not only can such a movement raise funds directly, but it also communicates to businesses and governments that this is an issue worth supporting. An instructive example to look at here is the work of Mary Lasker and Sydney Farber to bring about the “War on Cancer”. Through galvanizing the public with efforts such as the “Jimmy Fund”, they effected social and political change on the issue, and helped turn cancer from a pariah disease into a national priority. If we all work together to build an inclusive and action-orientated movement, we can do the same.

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

 

G. Stolyarov II Interviews Demian Zivkovic Regarding the D.N.A. – Gene Therapies Congress

G. Stolyarov II Interviews Demian Zivkovic Regarding the D.N.A. – Gene Therapies Congress

The New Renaissance Hat
G. Stolyarov II and Demian Zivkovic
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Mr. Stolyarov invited Demian Zivkovic, President of the Institute of Exponential Sciences (IES), to discuss the forthcoming Designing New Advances (D.N.A.) Gene Therapies Congress in Utrecht, The Netherlands.

The interview took place on Sunday, June 19, 2016, at 11 a.m. US Pacific Time. Watch the recording here.

The D.N.A. Congress is scheduled to occur on July 9, 2016, and will feature speakers such as Oliver Medvedik, Aubrey de Grey, Elizabeth Parrish, Keith Comito, and Tatjana Kochetkova. This event receives the strong endorsement of both The Rational Argumentator and the Nevada Transhumanist Party.

Read the announcement of the D. N. A. Congress here.

Contribute to the fundraiser for the D. N. A. Congress on Indiegogo  and Generosity.

DNA_Interview_CoverDemian Zivkovic is the president of the Institute of Exponential Sciences  (Facebook  / Meetup) – an international transhumanist think tank / education institute comprised of a group of transhumanism-oriented scientists, professionals, students, journalists, and entrepreneurs interested in the interdisciplinary approach to advancing exponential technologies and promoting techno-positive thought. He is also an entrepreneur and student of artificial intelligence and innovation sciences and management at the University of Utrecht.

Demian and the IES have been involved in several endeavors, such as organizing lectures on exponential sciences, interviewing experts such as Aubrey de Grey, joining several of Mr. Stolyarov’s futurism panels, and spreading Death is Wrong – Mr. Stolyarov’s illustrated children’s book on indefinite life extension – in The Netherlands.

Demian Zivkovic is a strong proponent of healthy life extension and cognitive augmentation. His interests include hyperreality, morphological freedom advocacy, postgenderism, and hypermodernism. He is currently working on his ambition of raising enough capital to make a real difference in life extension and transhumanist thought.

D.N.A. Congress Announcement by the Institute of Exponential Sciences

D.N.A. Congress Announcement by the Institute of Exponential Sciences

The New Renaissance HatInstitute of Exponential Sciences
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Editor’s Note: The forthcoming D.N.A. Congress in Utrecht, The Netherlands, hosted by the Institute of Exponential Sciences, devoted to discussions of gene therapies, receives the strong endorsement of both The Rational Argumentator and the Nevada Transhumanist Party. The D.N.A. Congress offers a promising venue to discuss the potential for gene therapies to cure diseases, lengthen lifespans, and improve quality of life for millions of people in the coming years and decades.

~ Gennady Stolyarov II, Editor-in-Chief, The Rational Argumentator, June 5, 2016

D.N.A CONGRESS PRESS RELEASE:

The Institute of Exponential Sciences (IES) has a large announcement to make. We are organising D.N.A – The largest European congress on human gene therapies, featuring speakers such as Aubrey de Grey, Liz Parrish, Oliver Medvedik and others.

Our event has been endorsed by LEAF, Heales VZW, BioViva, SENS Research Foundation, Singularity Network, People Unlimited, The Rational Argumentator, and many others. The event will be covered by national media and will be broadcasted online.

To make this vision a reality, we need your support. Share this message and donate today. Thank you!

IES needs your support to help make this vision a reality. Click here to donate to our crowdfunding campaign.

D.N.A – Designing New Advances: The second large Institute of Exponential Sciences event is coming to Utrecht

 

DNADemian Zivkovic

Utrecht – After a successful event last year in May, the grand congress is ready for a second edition. With a new name, we hope to make exponential sciences more approachable to the general public and bring people in the field closer together. The Institute of Exponential Sciences congress 2016 will be held at RASA podium on the 9th of July. The main theme of the event is gene therapies and cutting-edge applications of such therapies, such as health extension and interventions against human aging. To guarantee a great event, we have invited some of the biggest names in the field. Our guest speakers will be as follows:

Opening the event will be Oliver Medvedik, Ph.D, director of scientific programs at Genspace. Dr. Medvedik has earned his Ph.D at Harvard Medical school in the biomedical and biological sciences program. Since graduating from Harvard, he has worked as a biotechnology consultant, taught molecular biology to numerous undergraduates at Harvard, and mentored two of Harvard’s teams for the international genetically engineered machines competition (IGEM) held annually at M.I.T.

Our second speaker is Aubrey David Nicholas Jasper de Grey, Ph.D, an English author, Chief Science Officer of the SENS Research Foundation, and editor-in-chief of the academic journal Rejuvenation Research. Aubrey de Grey is well known for his focus on regenerative medicine and views on human aging. He will take the stage talking about the applications of current and upcoming technologies and studies which hold the potential to greatly extend our healthy lifespan.

Our third speaker is Tatjana Kochetkova, Ph.D, who is a fellow of the Institute of Exponential Sciences and a bioethicist. Dr. Kochetkova will follow up discussing the ethical and philosophical side of the technology and will address questions of what exponential technologies in biotech mean for society.

Our fourth speaker is Elizabeth Parrish, a fellow of the Institute of Exponential Sciences and the Founder and CEO of BioViva Sciences Inc, a Delaware corporation based in Seattle, WA, with labs and participating clinics in South/Central America where the majority of practical work is carried out. BioViva has been noted for being the first corporation in the world to treat a patient with gene therapy to reverse aging. The woman who wants to genetically engineer you will cover the basics of BioViva’s approach and vision for the the future, as well as the potential that gene therapies hold for radically improving our health and lives in the future.

Our fifth speaker will be Keith Comito, who is the founder and president of the Life Extension Advocacy Foundation (LEAF), a 501(c)(3) non-profit organization and a partner of the Institute of Exponential Sciences. Through LEAF, he operates the crowdfunding platform Lifespan.io, which supports biomedical research aimed at extending healthy human lifespan. He also serves as policy coordinator for the Global Healthspan Policy Institute, which facilitates relationships between researchers and government to advance initiatives in support of healthy life extension.

About Institute of Exponential Sciences

The Institute of Exponential Sciences is an international innovation-oriented think tank, outreach organisation, and networking platform based in the Netherlands, in the city of Utrecht. Its main activities include organising lectures and conferences, providing quality consultancy on innovation and exponential technologies, and collaborating with student organisations and universities in educating the public on the importance of exponential technologies.

It was founded by members of its predecessor, the Arma’thwynn society, which was a student group of like-minded young academics in the Netherlands. After organising events and attracting a very diverse and professional team of entrepreneurs, academics, and journalists, the society decided to move past student politics and make the move towards professionalism.

The Institute of Exponential Sciences is the result of that decision. After organising successful events (the largest of which was their symposium in April, 2015), the Institute of Exponential Sciences formalised its mission and reached out towards a process of international collaboration with other entities which share a techno-positive vision. The institute strives towards excellence in providing the best information and resources related to the issues relevant in the rapidly advancing technological society we live in.

The IES approach is focused on providing interdisciplinary education in the fields of exponential technologies such as artificial intelligence, bio-informatics, gene therapies, 3D-printing, augmented reality, and neural interfacing. We also provide a networking platform which allows entrepreneurs, scientists, journalists, and students to get in touch with others with similar ideas so that they may create the technologies of tomorrow. The IES strives not only to improve the speed of development of these technologies, but also to show the public the amazing possibilities technology provides for society.

IES and the IES logo are either registered trademarks or trademarks of IES Foundation in the Netherlands and/or other countries. All other products and/or services referenced are trademarks of their respective entities.