$54,000
$15,970

Progress in SENS Rejuvenation Research Over the Past 15 Years

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.

2002

2003

  • 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.

2004

  • 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.

2005

2006

2008

  • 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.

2009

  • 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.

2010

  • 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.

2011

  • 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.

2012

  • 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.

2013

  • 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.

2014

  • 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.

2015

  • 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.

2016

2017, so far...

Comments

Great summary. Thanks, Reason!

Posted by: Antonio at July 1st, 2017 2:54 AM

Good stuff.

Posted by: Steve Hill at July 1st, 2017 4:55 AM

Very useful timeline which helps getting a grasp of the progress, thank you for compiling these events Reason.

Posted by: Spede at July 1st, 2017 6:49 AM

I've always been a person that have taken value in all sorts of history and value people who study their family tree and takes notes during their lives. And I takes notes of most things in my life including things like this that I value, but taking these historical notes as they happened I had forgotten or hadn't capacity to. So Im glad someone else has done.

Posted by: Norse at July 1st, 2017 11:10 AM

That antibody that clears AB in 2016 also exhibits dose dependant ARIA and so actually looks like a bust. Some company needs to pick up catabolic IgM antibody research. Perhaps the Methuselah Fund should invest in Sundhir Paul's company Covalent Biosciences? The payoff could be huge. Or would this require more cash than the MF has?

Posted by: Jim at July 1st, 2017 8:22 PM

@Jim That doesn't necessarily mean aducanumab is a bust. It just means the treatment needs to start early and the dose needs to be low. Also from what I remember it seems like ARIA was affecting people with the APOE4 gene specifically.

One problem with anti-aging therapies and therapies for age related conditions is the strange and quite honestly completely unrealistic expectation of perfect drugs being developed in the near future. You should know enough about medicine at this point Jim, to know that is not realistic or rational.

If Aducanumab works well enough and slows down the progression of AD, it should be approved. We could throw it in the bin with the rest of the AD drugs developed so far, but the next one that works might not come for 10 or 20 years, I don't think that is a valid option if you consider how many people's lives and health could have been extended in the meantime, maybe even allowing them to live until the next viable drug is developed - a slim chance but better than no chance.

Posted by: Anonymoose at July 2nd, 2017 9:29 PM

@Matthias F: Thanks for finding that; it should be in there, and I've added it.

Posted by: Reason at July 3rd, 2017 7:37 AM

Hello there,

It's an incredible progress so far! However, there may be people interested in funding someone who is looking to fight aging and cannot understand much of this report.
What I would suggest is to create a simplified summary of what you have achieved so far, regarding for example how far is a drug to become a reality, the possible effects of these possible drugs on diseases, how would an anti aging treatment work (injections, pills, ...?), how would it work on a person already aged, etc, etc...

Thank you!

Pedro

Posted by: Pedro Gomes at August 29th, 2017 3:00 PM

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