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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.
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.

 

Jason Hope on Philanthropy – Article by Reason

Jason Hope on Philanthropy – Article by Reason

The New Renaissance Hat
Reason
November 30, 2015
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Jason Hope, you might recall, has provided half a million dollars in research funding to the SENS Research Foundation, used to establish a SENS laboratory at Cambridge in order to push forward with the Foundation’s AGE-breaker program. AGE-breakers are drugs or other treatments capable of breaking down advanced glycation end-products (AGEs). These are a class of metabolic waste product that accumulate in our tissues to cause significant harm that includes the progressive loss of elasticity in skin and blood vessels.

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

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

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

Philanthropy

Quote:

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

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

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

A 21st-Century Philanthropic Model For Philanthropy

Quote:

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

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

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

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

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.

SENS Research Foundation Joins the Global #GivingTuesday Movement – Press Release by SENS Research Foundation

SENS Research Foundation Joins the Global #GivingTuesday Movement – Press Release by SENS Research Foundation

The New Renaissance Hat
SENS Research Foundation
November 28, 2015
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Every Dollar Contributed Up to the First $5,000 Will Be Quadrupled, Turning into $20,000.
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MOUNTAIN VIEW, Calif. — November 24, 2015 — The SENS Research Foundation (SRF), a non-profit organization focused on transforming the way the world researches and treats age-related disease, has joined #GivingTuesday, a global day of giving that harnesses the collective power of individuals, communities and organizations to encourage philanthropy and celebrate generosity worldwide. Every dollar donated to SRF up to the first $5,000 will be quadrupled, making every dollar raised turn into $20,000.

Occurring this year on December 1, #GivingTuesday is held annually on the Tuesday after Thanksgiving (in the U.S.) and the widely recognized shopping events Black Friday and Cyber Monday to kick-off the holiday giving season and inspire people to collaborate in improving their local communities and to give back in impactful ways to the charities and causes they support.

SENS Research Foundation is aiming to reach a goal of $20,000 with the help of contributors who have pledged to match each dollar raised up to the first $5,000. The Croeni Foundation, a philanthropic organization dedicated to giving, the environment and health, has pledged to match the first $5,000 raised dollar for dollar. The foundation gave SRF an unrestricted $5,000 earlier this year, as well. Aubrey de Grey, CSO of SENS Research Foundation, has offered a dollar for dollar matching challenge up to $5,000. And Fight Aging! will match every dollar up to $125,000 through December 31, 2015. Fight Aging! encourages the development of medical technologies, lifestyles, and other means to help people live comfortably, healthily, and capably for as long as they desire.

“We are looking forward to participating in #GivingTuesday for a second year, and offer our thanks to Jan Croeni and the Croeni Foundation, as well as Aubrey de Grey and Fight Aging! for their support,” said Jerri Barrett, vice president of outreach, SENS Research Foundation. “Today’s cost for the treatment and care of chronic diseases of aging costs around $40,000 per second and will only continue to go up, as we spend more money per patient, while the number of patients is increasing. As a society, we need to change our ways and start treating age-related diseases more intelligently. The funds we raise on #GivingTuesday will help facilitate our efforts to do just that, as we work to continue learning how to prevent or reverse age-related diseases.”

Those who are interested in joining SENS Research Foundation’s #GivingTuesday initiative can donate at www.sens.org/donate. To learn more about #GivingTuesday participants and activities or to join the celebration of giving, please visit: http://www.givingtuesday.org/

About SENS Research Foundation (SRF)

SENS Research Foundation is a 501(c)(3) nonprofit that works to research, develop, and promote comprehensive regenerative medicine solutions for the diseases of aging. SRF is focused on a damage repair paradigm for treating the diseases of aging, which it advances through scientific research, advocacy, and education. SENS Research Foundation supports research projects at universities and institutes around the world with the goal of curing such age-related diseases as heart disease, cancer, diabetes and Alzheimer’s disease. Educating the public and training researchers to support a growing regenerative medicine field are also major endeavors of the organization that are being accomplished though advocacy campaigns and educational programs. For more information, visit www.sens.org.

Media Contact:
Jerri Barrett
408-204-7229
jerri.barrett@sens.org

Google Life Sciences to Fund Heart Disease Program – Article by Reason

Google Life Sciences to Fund Heart Disease Program – Article by Reason

The New Renaissance Hat
Reason
November 22, 2015
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An interesting next step from Google Life Sciences: they are putting forward $50 million in search of a laboratory to propose a program that pushes forward the state of the art in research and treatment of heart disease. Spent over ten years, that would produce an organization about the present size of the SENS Research Foundation, or a tenth of the Buck Institute, for purposes of comparison – and smaller than many of the research groups presently dedicated to the study of heart disease. So this is a sizable and welcome investment in medical research, but the significance is overhyped by the reporting organization here; no-one is going to cure heart disease with a $50 million project, since heart disease is caused by aging, and in the most general sense. This is an effort to change the funding landscape, stir things up, and make some progress.

If you walk through the list of forms of cell and tissue damage that causes degenerative aging, near every one of them contributes to structural failure of the cardiovascular system. The loss of stem cell activity and consequent decline in repair of tissues is only one of these: oxidized lipids that contribute to atherosclerosis in blood vessel walls; extracellular cross-links stiffen blood vessel walls and cause hypertension and consequent structural weakening in the heart; senescent cells wreck havoc on all the tissues they accumulate in; transthyretin amyloids that accumulate with age are implicated in heart disease via their ability to clog the cardiovascular system; and the loss of lysosomal function in long-lived cells, including those of the heart, progressively damages their function. Curing heart disease, removing it from the picture, requires treatments that effectively address near all of the causes of aging.

Quote from “Google Aims a $50 Million Moonshot at Curing Heart Disease” by Davey Alba, WIRED, November 16, 2015:

Cardiovascular disease people on Earth than anything else – over 17 million a year, and the number keeps going up. Of those deaths, more than 40 percent is due to coronary heart disease. Medicine has drugs that can treat it and practices that can help prevent it, but nobody really knows what causes it or how to cure it. Now, Google and the American Heart Association aim to change that by dropping a $50 million funding bomb on the problem. And as you might expect from a Silicon Valley giant that believes in moving fast and breaking things – an approach that hasn’t always transferred well to basic scientific research – the company isn’t spreading the money around. Google Life Sciences and the AHA said the money would go to one team over five years. “Traditional research funding models are often incremental and piecemeal, making it difficult to study a long-term, multifaceted subject. AHA and Google Life Sciences have committed to a bold new approach.”

The AHA, already the largest funder of cardiovascular research in the US outside of the federal government, says the program will be its most heavily funded initiative in nearly a century. Applications begin in January and if all goes according to plan, they’ll be due by February 14th. (Valentine’s Day. Get it?) If you want the $50 million, your idea has to fit on a single page. And Google won’t take a financial or intellectual property stake in the results. The organizations hope that the program will accelerate the field of heart research much like Google’s self-driving car eventually compelled the entire automobile industry to follow its lead.

Link: http://www.wired.com/2015/11/google-aims-a-50-million-moonshot-at-curing-heart-disease/

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.

International Longevity Day – October 1, 2015 – Press Release by Ilia Stambler

International Longevity Day – October 1, 2015 – Press Release by Ilia Stambler

The New Renaissance HatIlia Stambler
August 30, 2015

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International-Longevvity-Day Dear friends,

There has been emerging a tradition by longevity researchers and activists around the world to organize events dedicated to promotion of longevity research on or around October 1 – the UN International Day of Older Persons.

This day is sometimes referred to in some parts of the longevity activists community as the “International Longevity Day”. As this is the official UN Day of Older Persons, this provides the longevity research activists a perfect opportunity, perhaps even a perfect “excuse”, to emphasize the importance of aging and longevity research for the development of effective health care for the elderly, in the wide public as well as among decision makers.

The critical importance and the critical need to promote biological research of aging derives from the realization that tackling the degenerative processes and negative biological effects of human aging, at once and in an interrelated manner, can provide the best foundations to find holistic and effective ways for intervention and prevention against age-related ill health. Such an approach has been supported by scientific proofs of concept, involving the evidential increase in healthy lifespan in animal models and the emerging technological capabilities to intervene into fundamental aging processes. The focus on intervention into degenerative aging processes can provide solutions to a number of non-communicable, age-related diseases (such as cancer, heart disease, type 2 diabetes and neurodegenerative diseases), insofar as such diseases are strongly determined by degenerative aging processes (such as chronic inflammation, cross-linkage of macromolecules, somatic mutations, loss of stem cell populations, and others). This approach is likely to decrease susceptibility of the elderly also to communicable, infectious diseases due to improvements in immunity. The innovative, applied results of such research and development will lead to sustainable, economically viable solutions for a large array of age-related medical and social challenges, that may be globally applicable. Furthermore, such research and development should be supported on ethical grounds, to provide equal health care chances for the elderly as for the young.

Therefore it is the societal duty, especially of the professionals in biology, medicine, health care, economy and socio-political organizations, to strongly recommend greater investments, incentives and institutional support for the research and development dealing with the understanding of mechanisms associated with the human biological aging process and translating these insights into safe, affordable and universally available applied technologies and treatments.

October 1 – the International Day of Older Persons — provides the researchers and advocates an opportunity to raise these points and make these demands.

http://www.longevityforall.org/the-critical-need-to-promote-research-of-aging-around-the-world/

In 2013, events during or around that day – ranging from small meetings of friends to seminars and rather large conferences, alongside special publications, distributions of outreach materials (petitions and flyers) and media appearances – were held in over 30 countries, and in 2014 in over 20 countries. (Sometimes the events’ dates vary several days around October 1, or even through the entire month of October, designated as the “International Month of Older Persons” or the “International Longevity Month”, and sometimes the events are organized independently and without prior knowledge of other events, but they are all nonetheless unified by the common action and purpose.)

http://www.longevityforall.org/october-1-international-day-of-older-persons-longevity-day-2013-2014/

Let us maintain and strengthen this tradition! Let us plan and organize a mutually reinforcing network of events worldwide. If you plan to organize an event for that day – either live meetings or on-line publications and promotions – please let know. Together we can create an activism wave of strong impact. 

Following the collection of an impressive number of longevity promoting events worldwide in honor of that day, a general public appeal will be issued, both widely disseminated and addressed to relevant officials, both governmental and supra-governmental. Yet, the strength of the appeal will depend on the strength of all the individual events and actions.

Among the materials for discussion, distribution and promotion, one may use the position paper on the “Critical need to promote research of aging and aging-related diseases to improve health and longevity of the elderly population”, briefly describing the rationales, technologies and policies needed to promote this research. The position paper is available in 9 languages and can serve as a “universal advocacy paper” both for the grass roots discussions and promotions and for the outreach to officials: http://www.longevityforall.org/the-critical-need-to-promote-research-of-aging-around-the-world/. Also one may use in the preparation a presentation briefly listing some topics in longevity science promotion, such as the feasibility and desirability of achieving healthy longevity and public actions that can be taken to achieve it – http://www.longevityhistory.com/articles/ab7.php – or any other materials of your choice.

So far, events for that day – including meetings, publications and promotions – are already planned to be held around the world, in over 30 countries on 5 continents, including:

In the US, a conference will be held at the headquarters of the International Society on Aging and Disease (ISOAD), at the University of North Texas Health Science Center, in Fort Worth, Texas. This action will be endorsed and promoted by the US Healthspan Campaign (http://www.healthspancampaign.org/).

The Longevity Day action will also be promoted by the US Transhumanist Party, during their campaign tour that coincides with October 1.

Also in the US, online promotions will be held by the MILE campaign and by the Christian Transhumanist Association.

MILE-Panel-Cover

A special promotion will be done by LEAF – Life Extension Advocacy Foundation – via its crowdfunding platform for longevity research (http://www.lifespan.io/).

A fundraising action will be launched on that day for SENS Research Foundation by Fight Aging (https://www.fightaging.org/fund-research/).

In Israel, a seminar will be held in Bar Ilan University, by the Israeli Longevity Alliance. Toward that day, Israeli activists will also freely distribute an e-book on the history of longevity research (http://www.longevityhistory.com/).

In Moscow, Russia, a conference will be organized by the Russian Longevity Alliance. Another large conference will take place in Moscow, on the “Quality of Life of Older Persons”, supported by the Gerontological Society of the Russian Academy of Sciences, focusing on geroprotective substances and therapies.

In Gomel, Byelorussia, at the end of September, a conference will take place on the general subject of Radiobiolgy, at the Institute of Radiobiology of the National Academy of Sciences of Byelorussia, with a leading section on the biology of aging and longevity (“gerontological aspects of man-made factors”).

Another  small conference will take place in New Delhi, India, organized by the Solutions For the Future, with the help of India Future Society, and ISOAD India.

A series of events is planned in Pakistan, by the Pakistan National Academy of Young Scientists and the Universities of Lahore and of Malakand. The newly formed Pakistan Aging Research Society (PARS) organizes an entire month long campaign, “Go for Life” – from September 1 until October 1 – to encourage physical activity of older persons.

In Rome, Italy, a conference will be organized by the Italian Transhumanist Association and the Italian Longevity Alliance.

Additional meetings and promotions are planned by the European Healthy Life Extension Society (HEALES) in Brussels, Belgium, including a Competition for the Best Short Film on Life Extension.

A conference on longevity/life-extension science will be held by the Waag Society – Do It Together Bio in Amsterdam, Netherlands.

In Germany, meetings will be held by two new officially registered political parties that emphasize the development of biomedical research in their programs: in Berlin, by the German Health Research Party and in Stuttgart by the German Transhumanist Party.

An online promotion (videoconference) in Spanish will be organized by the Venezuela Longevity Alliance (together with activists from accross Latin America). A similar videoconference (to be recorded) in Portuguese will be organized for Brazil by the Brazil Longevity Alliance.

A pro-longevity documentary promotion will be done in Helsinki by Longevity Finland – Pitkäikäinen Suomi.

A meeting will be held in Stockholm, Sweden, by Aldrandefonden/Svenska Livsförlängningssällskapet SLFS – Swedish Life Extension Society.

In the UK, the London Futurist community will celebrate longevity research as a part of a discussion of emerging technologies in London.

In Larnaca, Cyprus, the ELPIS Foundation, together with the local gerontological community, will hold a seminar “Health in Older Life” and a local TV show in honor of that day.

In Perth, Australia, a meeting will be held by the “Healthy Longevity Philosophy” society. Another promotion will be done by Science, Technology and the Future society in Melbourne, Australia.

In Kiev, Ukraine, a seminar will be held on behalf of the Kiev Institute of Gerontology of the Ukrainian Academy of Medical Sciences.

In Beijing, China, a meeting will be organized by the Technium community.

In Uganda, the Kasese Freethinkers Sports Academy will educate about the connection between physical activity and longevity.

A mini-seminar will be held in Lekki, Lagos, Nigeria, by Longevity Nigeria group.

In Romania, a conference will be held at Äna Aslan National Institute of Gerontology and Geriatrics, in Bucharest, toward the end of October, with earlier promotions.

In Vietnam, Hanoi, the Vietnam Public Health Association will hold a conference on the Mental Health of the Elderly, emphasizing biomedical research on neurodegenerative diseases.

In Singapore, a seminar on biology of aging will be organized at the National University of Singapore. This will precede a large Biology of Aging Conference organized by the Singapore Immunology Network (A*Star) – not “officially” a part of the “Longevity Day” events, but perhaps of the “Longevity Month.”

At about the same time, the 10th Asia / Oceania Congress of Gerontology and Geriatrics 2015 for “Healthy Aging Beyond Frontiers” will take place in Chiangmai, Thailand, including sections on biology of aging.

In Paris, France, a seminar will be organized at the Biopark Cancer Campus, University Paris Sud.

In South Korea, the Korean Branch of Solutions for the Future will organize a meetup in Seoul.

In Switzerland, Zurich, the Swiss Longevity Alliance will have a presentation on longevity research. This will shortly follow a large international symposium on geroprotectors in Basel.

In Poland, the Warsaw University Students Association will support the organization of a discussion on life extension science.

In Canada, at Huntington University, an event will be held by the Canadian Institute for Studies in Aging (CISA). In Alberta University, Canada, a special discussion on Technology and the Future of Medicine will be dedicated to that day.

In Iran, a study group will be conducted in Tehran on behalf of the Iran Longevity Alliance: http://www.iranlongevity.com/.

Yet another study group will be held in Cairo, Egypt, by the Egypt Longevity Alliance: http://www.egyptplus.org/.

And yet another free discussion of longevity science will take place in Tirana, Albania – the first longevity research activism event in the country.

In Bulgaria, events toward the International Longevity Day will start earlier in September with a conference in Ravda, organized by the University for National and World Economy, Department of Management and BASAGA – Bulgarian Academic Simulation and Gaming Association, including a section on Futurism, Transhumanism and Longevity, and continuing up to the date itself with more live and online discussions and publications and a special appeal in honor of that day.

In Tokyo, Japan, Exponential Technologies Institute will hold a meetup on longevity science in the framework of Tokyo-Singularity-Meetup.

A meeting will be held in the National Library in Tbilisi, Georgia, by activists of the Georgian Longevity Alliance, including presentations on the development of longevity science in Georgia and the world, and debates.

More events and expressions of support are expected to be initiated in the very near time in different countries.

Please add your support and more events and publications for this initiative! If you would like to get involved, please let know!

You are also welcome to promote this initiative on social media:

https://www.facebook.com/events/1017229998296364/

https://www.facebook.com/LongevityDay

Preparations for the next year’s International Longevity Day – October 1 – already started as well. The next global conference of the International Society on Aging and Disease (ISOAD) will take place in Stanford on October 1-2, 2016. The topics will range from interventions for longevity through stem cell research, genetics and systems biology of aging, to public support for aging research. The submission of abstracts and proposals is already started and welcome. And a conference is being planned in Brussels, for September 29-October 1, 2016, by the European Healthy Life Extension Society – Heales.

Hopefully, thanks to these and many other events, in this year and in the years to come, the importance of biological aging and longevity research will gradually become a strong theme of the international healthcare agenda, for the elderly and for the entire population.

Ilia Stambler, PhD.

Outreach coordinator. International Society on Aging and Disease (ISOAD)

http://isoad.org/

ilia.stambler@gmail.com

Thank you!

Ilia Stambler, Ph.D. is an IEET Affiliate Scholar, researcher at Bar-Ilan University, Israel, and activist at the International Longevity Alliance. He is author of A History of Life-Extensionism in the Twentieth Century.
 
He studied biomedical engineering at the Moscow Polytechnical Institute, biology at the Technion, Israel Institute of Technology, and earned his MA in English literature from Bar-Ilan University. He earned his Ph.D. at the Department of Science, Technology, and Society, at Bar-Ilan University. His thesis subject, and his main interest, is the History of Life-Extensionism in the Twentieth Century.
 
In addition, Ilia authored Life extension — a conservative enterprise? Some fin-de-siècle and early twentieth-century precursors of transhumanism, Demonstration for Radical Life Extension in Tel Aviv, and Heroic Power in Thomas Carlyle and Leo Tolstoy, and coauthored Breast cancer detection by Michaelis–Menten constants via linear programming, and Comparative analysis of cell parameter groups for breast cancer detection. Read the full list of his publications!
 
He speaks Hebrew, English, Russian, German, and Yiddish. He is active in the Israeli chapter of Humanity Plus, the Israeli Society for the Biology of Aging, and the International Longevity Alliance.
 
Watch Demonstration for Radical Life Extension in Tel Aviv 5: Ilia Stambler. Read 10 Answers by Ilia Stambler. Visit his Facebook page. Read his Google+ profile and his LinkedIn profile. Read his blog Singularity | Life Extension | Transhumanism (Hebrew).

Protein Modification as a Biomarker of Aging – Article by Reason

Protein Modification as a Biomarker of Aging – Article by Reason

The New Renaissance Hat
Reason
April 19, 2015
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The development of fairly consistent, accurate means to measure biological age – as opposed to chronological age – from a tissue sample is an important thread in aging research. Aging is a process of damage accumulation, and rejuvenation would be achieved through damage repair. Research and development aimed at significant extension of healthy life span can only become cost-effective given good ways to measure damage, however. There must be some reliable means to quickly assess the results of a treatment that claims a degree of rejuvenation through the partial repair of a specific form of cellular or molecular damage. In some cases this might seem easy. Take senescent cell clearance, for example: you run the therapy in mice, and compare a range of measures known to scale by senescent cell count in tissue samples before and after the treatment regimen. However, all that really tells you is how well the therapy clears senescent cells. All aspects of biology interact with one another, and age is a global phenomenon. To determine how aged an individual is and how effective a treatment might be when it comes to the practical outcome of additional healthy life span added there is presently little to be done other than wait and see.

The biggest challenge in the development of life-extending therapies is funding and cost. On the one hand there is far too little funding directed towards finding ways to treat aging. On the other hand effectively evaluating an alleged means of treating aging currently requires lifespan studies, and even in mice that takes far too long and costs far too much to be done casually. If there were standardized, quick and easy markers of physiological age that could be assessed before and after a treatment, then this research and development might be able to proceed ten times as rapidly, and evaluation of possible therapies would be open to far more research groups. There are many, many more laboratories with the capacity and funding to carry out a speculative $100,000 study versus a speculative $1,000,000 study.

All of this is to explain why there is considerable interest in developing a cheap biomarker of aging that can reliably assess physiological age from a tissue sample. No-one wants to run a five-year mouse study if there is a ten-minute alternative that produces an answer of about the same accuracy. That ten-minute alternative doesn’t yet exist, but some lines of research seem promising, such as work on DNA methylation patterns that appear to be fairly consistent among individuals over the course of aging. There is also the suggestion that the approach should be to measure the fundamental forms of damage thought to cause aging – but all of them, not just the one being treated by the therapy under consideration. At the present time that might be more onerous than finding a good set of secondary consequences that are reactions to damage, such as epigenetic changes.

The open-access paper linked below covers a fairly wide range of topics. The structures of our cells and tissues are built of proteins, and these proteins are constantly damaged and replaced. Many varied mechanisms toil constantly to remove proteins and cellular components as soon as they show damage or dysfunction. Nonetheless the difference between young tissue and old tissue is that old tissues have far more damage: misfolded proteins, malfunctioning structures inside cells, metabolic waste products such as advanced glycation endproducts (AGEs) gumming together structures in between cells, and so on and so forth. The damage leaks through, and even damage repair mechanisms are not invulnerable; they falter with age due to much the same set of issues as causes dysfunction elsewhere. In the future repair technologies, such as those outlined in the SENS proposals, will bring about rejuvenation by reversing these forms of damage. Since these issues are a part of full set of causes of aging, they are also potential markers of aging.

Protein modification and maintenance systems as biomarkers of ageing

Changes in the abundance and post-translational modification of proteins and accumulation of some modified proteins have been proposed to represent hallmarks of biological ageing. Non-enzymatic protein glycation is a common post-translational modification of proteins in vivo, resulting from reactions between glucose or its metabolites and amino groups on proteins, this process is termed “Maillard reaction” and leads to the formation of advanced glycation endproducts (AGEs). During normal ageing, there is accumulation of AGEs of long-lived proteins such as collagens and several cartilage proteins. AGEs, either directly or through interactions with their receptors, are involved in the pathophysiology of numerous age-related diseases, such as cardiovascular and renal diseases and neurodegeneration.
 ***
Beside protein glycation, it is also well known that levels of oxidised proteins increase with age, due to increased protein damage induced by reactive oxygen species (ROS), decreased elimination of oxidized protein (i.e. repair and degradation), or a combination of both. Since the proteasome is in charge of both general protein turnover and removal of oxidized protein, its fate during ageing has received considerable attention, and evidence has been provided for impairment of the proteasome function with age in different cellular systems. Thus, these protein maintenance systems may also be viewed as potential biomarkers of ageing.
  ***
It is expected that a combination of several biomarkers will provide a much better tool to measure biological age than any single biomarker in isolation. For the most part, the markers based on proteins and their modifications that have been chosen are directly related with mechanistic aspects of the ageing process. Indeed, they are relevant to such important physiological features such as protein homeostasis and glycoprotein secretion that have been previously documented as being altered with age. Therefore, it is expected that they may be less influenced by other factors not necessarily related with ageing.
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.

Tomorrow Will Be Different From Today – Article by Reason

Tomorrow Will Be Different From Today – Article by Reason

The New Renaissance Hat
Reason
April 16, 2015
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We live in an era of very rapid change driven by technological progress. Today’s world is enormously different from that of three or four decades past: consider the pervasive effects of the revolution in communications and computing technologies that has taken place over that time. Yet, human nature being what it is, most of the people who lived through this profound shift in capabilities and culture are nonetheless very skeptical of claims that the future will look radically different from today in any important aspect. It is strange.

In particular the concept of actuarial escape velocity leading to thousand-year life spans is a very hard sell. People look at the large number that is very different from today’s maximum life span and immediately reject it out of hand, no matter the reasonable argument behind it. Any medical technology that produces some rejuvenation in old patients buys extra time to develop better means of rejuvenation. At some point the first pass at rejuvenation treatments will improve such that remaining healthy life expectancy grows at more than a year with each passing year. At that point life spans will become indefinite, limited only by accident or rare medical conditions not yet solved.

It doesn’t help that most of the public has very little knowledge of the present state of medical research in any field, never mind the specific details of how aging might be treated and brought under medical control. The only solution to that issue is to keep on talking: educate, advocate, and spread the word.

Quote:

It is likely the first person who will live to be 1,000 years old is already alive today. This is according to a growing regiment of researchers who believe a biological revolution enabling humans to experience everlasting youthfulness is just around the corner. At the epicentre of the research is Aubrey de Grey, co-founder or the California-based Strategies for Engineered Negligible Senescence (SENS) Research Foundation.

“The first thing I want to do is get rid of the use of this word immortality, because it’s enormously damaging, it is not just wrong, it is damaging. It means zero risk of death from any cause – whereas I just work on one particular cause of death, namely ageing.” de Grey said his research aims to undo the damage done by the wear and tear of life, as opposed to stopping the ageing process altogether. “If we ask the question: ‘Has the person been born who will be able to escape the ill health of old age indefinitely?’ Then I would say the chances of that are very high. Probably about 80 per cent.”

“The therapies that we are working on at the moment are not going to be perfect. These therapies are going to be good enough to take middle age people, say people aged 60, and rejuvenate them thoroughly enough so they won’t be biologically 60 again until they are chronologically 90. That means we have essentially bought 30 years of time to figure out how to re-rejuvenate them when they are chronologically 90 so they won’t be biologically 60 for a third time until they are 120 or 150. I believe that 30 years is going to be very easily enough time to do that.”

Link: http://www.news.com.au/technology/science/researchers-believe-a-biological-revolution-enabling-hu

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.

The 2014 Fight Aging! Fundraiser Starts Now: We’ll Match Your Research Donations with $2 for Every $1 Given – Article by Reason

The 2014 Fight Aging! Fundraiser Starts Now: We’ll Match Your Research Donations with $2 for Every $1 Given – Article by Reason

The New Renaissance Hat
Reason
October 4, 2014
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Note from the Editor: The Rational Argumentator strongly supports this matching fundraiser and encourages all readers to donate any sums of money to the SENS Research Foundation, in order to accelerate the basic research into and the development of cures for the debilitating diseases of old age. I personally made a donation of $100 on October 4, 2014, knowing that its impact will be tripled through a 2-for-1 additional contribution by the generous donors who established the matching fund. This is the time to leverage our resources and ensure that this literally vital research gets done as soon as possible. I am grateful to Reason of FightAging.org for his tireless efforts in advocating for life-extension research and spearheading campaigns to attract the funding that this area of science urgently needs.

~ Gennady Stolyarov II, Editor-in-Chief, The Rational Argumentator, October 4, 2014

***

It is that time again, and our 2014 matching fundraiser started October 1st 2014. From now until the end of the year, December 31st 2014, we will match the first $50,000 donated to the SENS Research Foundation with $2 for every $1 given. These funds will help to speed progress in ongoing scientific programs conducted in US and European research centers, their ultimate aim being to repair and reverse the causes of frailty and age-related disease.

The SENS Research Foundation is a 501(c)(3) charity and all US donations are tax-deductible. Donations from most European Union countries are also tax-deductible, though the details vary by location. Please contact the SENS Research Foundation to find out more.

The Matching Fund Founders Ask You to Join Us

Who are we? We are Christophe and Dominique Cornuejols, David Gobel of the Methuselah Foundation, Dennis Towne, Håkon Karlsen, philanthropist Jason Hope, Michael Achey, Michael Cooper, and Reason of Fight Aging! We are all long-time supporters of SENS research aimed at rejuvenation through repair of the known root causes of aging. The few types of cellular and molecular damage that accumulate in all of our tissues cause progressive dysfunction and eventual death for everyone – unless something is done to stop it. This cause is important enough for everyone to do their part, and for us that means putting up a $100,000 matching fund we want you to help draw down: for every dollar you donate, we will match it with two of our own.

Even Small Donations Make a Meaningful Difference

Early stage medical biotechnology research of the sort carried out at the SENS Research Foundation costs little nowadays in comparison to the recent past. The cost of tools and techniques in biotechnology has plummeted in the past decade, even while capabilities have greatly increased. A graduate student with $20,000 can accomplish in a few months what would have required a full laboratory, years, and tens of millions of dollars in the 1990s. All of the much-lamented great expense in modern medicine lies in clinical translation, the long and drawn out process of trials, retrials, marketing, and manufacturing that is required to bring a laboratory proof of concept into clinics as a widely available therapy.

The SENS Research Foundation is focused on early stage research, following a plan that leads to technology demonstrations in the laboratory. With a proof of concept rejuvenation therapy the world will beat a path to their doorstep in order to fund clinical translation. The real challenge is here and now, raising the funds to get to that step. A few tens of thousands of dollars means the difference between a significant project delayed indefinitely or that project completed.

To pick one example, last year the community raised $20,000 to fund cutting edge work in allotopic expression of mitochondrial genes, a potential cure for the issue of mitochondrial damage in aging. That was enough to have a skilled young researcher work on the process for two of the thirteen genes of interest over a period of months. It really is that cheap given an existing group like the SENS Research Foundation with diverse connections and access to established laboratories.

Your donations make a real difference.

Spread the Word, Tell Your Friends

Don’t forget to tell your friends about this fundraiser. Talk to your community, online and offline. Consider running local events to help meet our goal of raising $50,000 from a grassroots community of supporters. The more people who know about the prospects for near future therapies resulting from rejuvenation research of the sort carried out by the SENS Research Foundation, the easier it becomes to raise funds and obtain institutional support for these research programs in the future.

Launched at /r/Futurology and in Conjunction with Longevity Day

Take a look at the generous spirit displayed at /r/Futurology, the futurist Reddit community, when given the chance to help. Scores of people there have already donated modest sums to the cause in response to our fundraiser: many thanks to you all!

The 1st of October marks the launch of this fundraiser, but it is also the International Day of Older Persons, and the International Longevity Alliance would like this to become an official Longevity Day. This year, just like last year, groups of futurists around the world will be holding events to mark the occasion, and this includes the scientists and advocates present at the 2014 Eurosymposium on Healthy Aging.

Download the 2014 Fundraiser Posters

The full size graphics here are large enough for 24 x 36 inch posters, but are also suitable for page-sized fliers. The original Photoshop files are available on request, but are a little large to put up here. Make as much use of these as you like – please help to spread the word and help this fundraiser to meet its target.

Color design, 3600 x 5600 pixels suitable for 24 x 36 inch posters, 11.3MB
Color design, 2400 x 3600 pixels suitable for letter size, 6.3MB

Blue design, 7200 x 10800 pixels suitable for 24 x 36 inch posters, 13.1MB
Blue design, 2400 x 3600 pixels suitable for letter size, 3.8MB

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.

ALS, SENS, and Ice Buckets (or Lack Thereof) – Video by Gennady Stolyarov II and Wendy Stolyarov

ALS, SENS, and Ice Buckets (or Lack Thereof) – Video by Gennady Stolyarov II and Wendy Stolyarov

The New Renaissance Hat
G. Stolyarov II and Wendy Stolyarov
August 28, 2014
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Gennady Stolyarov II and Wendy Stolyarov, author and illustrator of Death is Wrong, respond to the ALS Ice Bucket Challenge.

References

Evidence of Donation to ALS Association
Evidence of Donation to SENS Research Foundation
ALS Association
SENS Research Foundation
Eternal Life Fan Club Website
Eternal Life Fan Club on Facebook
Death is Wrong Official Home Page