Reforming and rebuilding an entire field of medical research and development isn't an easy task, and sadly nor is it something that can be achieved overnight. A comprehensive reformation of the aging research community is nonetheless the goal of the SENS initiative, the Strategies for Engineered Negligible Senescence - a way to build rejuvenation therapies that work by repairing forms of cell and tissue damage that cause aging. SENS came into being precisely because aging research was not heading in the right direction: researchers were not attempting to treat aging as a medical condition, influential figures were in fact actively suppressing any sort of impetus in that direction, and where there were glimmerings of hope in the form of a few scientists interested in intervening in the aging process, these individuals were focused on strategies that could not possibly do more than slightly slow down age-related degeneration.
Over the past fifteen years SENS has progressed from a position statement and a vision for the end of aging, a set of ideas and supporting evidence only, to a modestly sized set of research programs that are now producing results, several non-profit foundations, a web of relationships with a outsized influence on the research community, and the clinical development of the first rejuvenation therapies. SENS has come a long way from the first meetings of a few like-minded researchers and advocates, just after the turn of the century. Now many researchers are openly talking about the causes of aging and the construction of therapies to meaningfully treat aging. The old suppression of this topic has crumbled entirely. It remains the case that most researchers are still stubbornly pursuing approaches that cannot have a large effect on human health and life span, but the initial battle to change the direction of the research community has been fought and won. Now it is just an increasingly vocal and public debate over how best to proceed, and here SENS will win in time as therapies that repair age-related molecular damage are proven to be far cheaper, more effective, and more reliable than other efforts.
We have come a long way, but one of the necessary parts of advocacy that I think that our community does poorly is the presentation of this growth and success of past years. There is so much we can point to, and show where and how we came together to make a difference, to change the course of research, to fund and build new advances, to change minds and gather allies. We don't do a good job when it comes to clearly showing the progression from (1) initial idea to (2) non-profit scientific foundations to (3) philanthropic support of research to (4) broader research community participation to (5) proof of concept technology demonstrations to (6) founding of biotechnology companies to (7) venture fundraising to (8) clinical trials of rejuvenation therapies. That long chain now exists nearly end to end for senescent cell clearance as a rejuvenation treatment, and all of the other potential branches of SENS research are underway in some form.
So with that in mind, the following timeline references some of the important developments and advances in rejuvenation biotechnology since the origin of the SENS program, from the slow and incremental start to the present more rapid pace. It is by design a high-level and sparse overview, as I wanted to capture the bigger picture without getting dragged down into the details. Watching early stage progress in research from year to year can be a frustrating process, but as senescent cell clearance demonstrates, once a field reaches the tipping point of viability and support, things then move very rapidly. Further, given that this all started with a few ideas and a little persuasion, it is certainly the case that mountains have been moved over the years, even if it feels all too slow on a day to day basis. There is much more to be done ahead, but all who have participated in the past should feel rightfully proud of what has been accomplished, and what continues to be accomplished today.
- The first of Aubrey de Grey's collaborative papers, describing SENS as a goal-driven approach to the treatment of aging as a medical condition, is published in the Annals of the New York Academy of Sciences.
- The Methuselah Foundation is created, and the founders launch the Mprize for longevity science, a research prize aiming to spur greater interest in extending healthy life spans.
- The first SENS-focused academic conference is held in the UK under the auspices of the International Association of Biomedical Gerontology.
- The Methuselah Foundation begins to assemble the 300, a core group of donors who go on to be influential in the course of advocacy and development of rejuvenation biotechnology. Their funds power the early work of the foundation, and some start their own initiatives in later years.
- An individual whose identity remains a mystery to this day makes a $1 million donation to the Methuselah Foundation to expand the Mprize purse.
- The Methuselah Foundation begins funding (a) LysoSENS research, searching for enzymes in soil bacteria capable of consuming age-related metabolic waste, and (b) allotopic expression of mitochondrial genes, aiming to remove the consequences of mitochondrial damage in aging.
- The Methuselah Foundation sponsors the Supercentenarian Research Foundation, supporting a program of autopsies of supercentenarians. Over the next few years this demonstrates transthyretin amyloidosis to be the majority cause of death.
- Peter Thiel publicly supports SENS research with a $3.5M grant.
- Researchers first demonstrate the creation of induced pluripotent stem cells, a foundation for much of the future of regenerative medicine to replace cells lost to aging.
- The Methuselah Foundation expands allotopic expression funding to support a French research group that will go on to establish Gensight Biologics on the strength of this work. The foundation also announces the commencement of research initiatives for most of the other SENS programs: clearing senescent cells, removing metabolic waste such as amyloid and cross-links, and investigation of alternative lengthening of telomeres (ALT) in the context of cancer.
- The first US SENS conference is held at UCLA.
- The SENS Research Foundation spins off from the Methuselah Foundation to focus entirely on SENS rejuvenation research.
- GSK and Pentraxin Therapeutics begin a collaboration to develop a therapy capable of clearing transthyretin amyloid.
- The Methuselah Foundation makes its first outside investment in the Organovo tissue printing startup.
- The SENS Research Foundation's yearly budget reaches $1 million. The foundation sets up a laboratory facility in Mountain View, California for ongoing intramural research projects.
- Jason Hope pledges $500,000 to the SENS Research Foundation to start a research program aimed at developing a viable cross-link breaker for glucosepane in humans.
- Researchers find that transplanting a young thymus into an old mouse restores immune function and extends life.
- Aubrey de Grey devotes the majority of his $16.5M net worth to funding SENS research.
- The SENS Research Foundation is funding either in-house or external research projects in all of the seven strands of SENS rejuvenation research. Some are very early stage, focused on building tools or discovery, while others are building the basis for therapies.
- The first demonstration of targeted senescent cell clearance is carried out by an independent research group, producing benefits in mice with an accelerated aging condition.
- The Methuselah Foundation launches the New Organ tissue engineering initiative.
- Gensight Biologics is founded to commercialize allotopic expression of mitochondrial gene ND4, based on the research program supported initially by the Methuselah Foundation, and later the SENS Research Foundation.
- The SENS Research Foundation demonstrates bacterial enzymes that can break down 7-ketocholesterol in cell culture.
- Methuselah Foundation supported tissue printing company Organovo becomes publicly traded on NASDAQ.
- Covalent Bioscience is founded to advance work on catalytic antibodies (or catabodies) to clear the amyloid associated with Alzheimer's disease.
- Gensight Biologics raises a $32M series A round.
- The Methuselah Foundation announces a $1 million research prize for liver tissue engineering as a part of the New Organ initiative. This year the foundation also sponsors organ banking initiatives at the Organ Preservation Alliance.
- The important Hallmarks of Aging position paper is published, the authors taking a cue from the SENS rejuvenation research proposals, but carving out their own view on damage and repair.
- Google Ventures launches Calico, adding a great deal of support to aging research with the size and publicity of the investment. Unfortunately Calico goes on to focus on areas of aging research unrelated to rejuvenation.
- Cenexys is founded to work on the creation of means to selectively destroy senescent cells in aged tissues.
- The Methuselah Foundation and SENS Research Foundation provide seed funding to launch Oisin Biotechnologies, to develop a method of targeted clearance of senescent cells.
- The SENS Research Foundation begins the Rejuvenation Biotechnology conference series, bringing together industry and academia to smooth the path for development of rejuvenation therapies.
- Following the Hallmarks of Aging, leading researchers publish their Seven Pillars of Aging position, again echoing the long-standing SENS view of aging and its treatment.
- The SENS Research Foundation funds development of catabodies to break down transthyretin amyloid, and the work shows considerable promise.
- Human Rejuvenation Technologies is founded to commercialize a treatment for atherosclerosis based on SENS Research Foundation LysoSENS program approaches to clearing metabolic waste compounds.
- The SENS Research Foundation's yearly budget reaches $5 million.
- The Spiegel Lab at Yale announces a method of creating glucosepane, a vital and to this point missing tool needed to develop glucosepane cross-link breaker drugs. This work was funded by the SENS Research Foundation.
- A research team demonstrates the first senolytic drug candidates capable of selectively destroying senescent cells. The number of candidate drugs increases quite quickly after this point.
- Pentraxin Therapeutics announces positive results in a trial of targeted clearance of transthyretin amyloid. Meanwhile, evidence continues to emerge from other groups for transthyretin amyloid to have more of an impact in age-related disease that previously thought.
- SENS Research Foundation work on sabotaging ALT to suppress cancer receives more attention. Meanwhile progress is reported on the other half of telomere extension blockade, interfering in the operation of telomerase, an area in which a number of groups are participating.
- The Methuselah Foundation makes a founding investment in Leucadia Therapeutics in order to pursue a novel approach to the effective treatment of Alzheimer's disease.
- The research program producing catabodies capable of breaking down transthyretin amyloid is transferred to Covalent Bioscience for clinical development.
- Ichor Therapeutics begins commercial development of a method of clearing metabolic waste from the retina, based on technology developed in the SENS Research Foundation LysoSENS program.
- Gensight Biologics demonstrates success in a trial of mitochondrial allotopic expression of ND4 as a way to treat inherited mutations of that gene. The underlying technology is proven. SENS Research Foundation scientists, meanwhile, successfully demonstrate allotopic expression of ATP6 and ATP8.
- After more than a decade of high profile failures, amyloid-β is finally cleared from the brain in a small human study using an immunotherapy approach.
- The SENS Research Foundation crowdfunds a drug discovery program to find candidates that can interfere in ALT, and thus suppress the telomere elongation that cancer depends upon.
- Cenexys is reformed as Unity Biotechnology with a focus on senolytic drugs. The researchers involved show that clearance of senescent cells in normal mice produces 25% extension of median life span. Later in 2016, the company raises $116M in venture funding.
- Other work on removal of senescent cells across the year shows restoration of function in aged lung tissue, and improved vascular health. New evidence reinforces the role of senescent cells in osteoarthritis, as well as in atherosclerosis, immunosenescence, and diabetic retinopathy
- The Methuselah Foundation launches a $500,000 research prize for tissue engineering in collaboration with NASA.
- Michael Greve pledges $10M to fund SENS research and startup biotechnology companies that emerge from that research.
2017, so far...
- There are now nearing ten different senolytic drug candidates with openly published evidence, and more in the pipeline.
- Oisin Biotechnologies announces that their senescent cell clearance technology can also be applied to cancerous cells, reporting successful animal studies for tumor ablation.
- Methuselah Foundation launches the Methuselah Fund to shepherd more rejuvenation-related biotechnology startups towards success.