Antonov Foundation donates $1M to SRF’s End of Year Campaign

At the end of each year, SRF launches our final fundraising campaign – the aptly named End of Year Campaign – to encourage our donors to donate during the most giving time of year. Most years we have good success in meeting our goal, in large part due to the multitude of donors who believe in our mission to end age-related disease.

2020 was a particularly difficult year for everyone. With the COVID-19 pandemic hitting across the globe, jobs being lost or postponed, families being separated, and loved ones dying, our foundation also took a hit. We struggled to find safe and effective ways to continue our life-saving research, both internally and externally. Our Education program suddenly had to find ways to host the students, or else close the program for this year. The enormously successful Undoing Aging Conference was postponed, then postponed again, as restrictions from various countries became more severe to battle the rise in infections.

This year, more than ever, our End of Year Campaign was vital to the survival of SENS Research Foundation and the work that we do to combat all causes of age-related disease and disability. This includes COVID-19, as the greatest predictor of death from this virus is age.

Despite all the challenges, a long-time supporter of ours came forward with a generous donation and a challenge to our base. 

Michael Antonov

The Michael Antonov Foundation was founded with a vision of extending average human lifespan to over 120 and enabling people to better understand the world and become masters of their own destiny. The foundation makes grants and gifts to 501(c)(3) organizations that perform human longevity-centered research and collaborates with industry players in order to maximize the impact of longevity-centered projects. Michael Antonov, the founder of the foundation, is a serial entrepreneur and philanthropist passionate about taking on a challenge to extend human lifespan and make them more meaningful. In addition to the foundation, Michael Antonov is the founder of Formic Ventures, an early stage longevity-focused venture capital firm and was previously the co-founder and Chief Software Architect at Oculus, where he helped revive the virtual reality industry.

Michael Antonov donated $400,000.00 to SRF outright at the beginning of our campaign, then set up a matching grant of up to $600,000.00 for our supporters to match. His generosity and vision for our cause encouraged eleven other supporters of SRF to turn his offer of doubling donations into a triple donation. The first $525,000.00 of support we received was tripled, and we are thrilled to announce that the full $600,000.00 of the original match was met. SRF raised a total of $2,335,443.46 in this year’s campaign.

Thank you, from all of us at SRF, for your ongoing support. It takes all of us strongly united as a community, to tackle the issues that we at SRF strive to solve. We would not be able to make the progress we do without the support of benefactors like Michael Antonov, and the dedication and generosity of every single donor, particularly during such trying times as we find ourselves currently.

Thank you again. SRF lives another day to #UnlockLongevity.

Catalysing ApoptoSENS

We are pleased to announce that the ApoptoSENS team led by Dr. Amit Sharma at the SRF Research Center has recently been granted a Catalyst award, courtesy of the Healthy Longevity Global Competition, to continue and expand their critical work on the interactions between senescent cells and natural killer (NK) cells.

The Healthy Longevity Global Competition, administered by the U.S. National Academy of Medicine (NAM) with support from Johnson & Johnson Innovation, will issue up to 24 Catalyst Awards per year between 2020 and 2022. Each Catalyst Award includes a $50,000 cash prize and travel costs to attend an annual Innovator Summit, beginning in summer 2021. The American Federation for Aging Research (AFAR) will collaborate with the NAM on the application and scientific review process.

The major consequence of unresolved DNA damage is a state of growth arrest termed cellular senescence. Although senescence can prevent mutated cells from transforming into cancer, it can also contribute to age-related disease – largely because senescent cells secrete pro-inflammatory factors, collectively known as the Senescence Associated Secretory Phenotype (SASP).

Strong correlations between the accumulation of senescent cells with increasing age and various negative outcomes, as well as the improvements in healthspan observed in several animal models upon their removal, have made senescent cells attractive targets for rejuvenation therapies. The ApoptoSENS strand of the SENS platform is dedicated to the development of those treatments.

Natural Killer (NK) cells are innate immune cells that surveil the body for precancerous cells and cells infected with viruses and other intracellular pathogens. Once the NK cells recognize a target (based on its display of activating and inhibitory receptors), they release cytotoxic proteins such as perforin and granzymes, which induce programmed death – apoptosis – in the target cells.

Recent reports indicate that NK cells can also selectively eliminate senescent cells in cell culture and animal models, opening up a new avenue to develop therapeutic interventions.

This field of research is still in its infancy, and there are several unanswered questions, such as:

  1. can senescent cells escape immune clearance by secreting or presenting decoy receptors, and
  2. how does immune senescence (NK cell aging) impact the cytotoxic potential of NK cells towards senescent cells?

Supported by the Catalyst Award, the ApoptoSENS team will now investigate whether the age-related loss of cytotoxic potential of NK cells toward senescent cells is reversible and, if so, whether and how this may provide routes for therapeutic intervention. If successful, this work will clear a major hurdle to realizing NK cell-based treatments for senescent cell elimination.

Tracking Down Glucosepane

Figure from Generation and Characterization of Anti-Glucosepane Antibodies Enabling Direct Detection of Glucosepane in Retinal Tissue.

The loss of physical function seen in aging tissues is partly due to the formation of irreversible crosslinks between proteins. A new paper in ACS Chemical Biology reports SRF-funded work in the lab of Yale’s Prof. David Spiegel on an antibody that specifically labels the major crosslink glucosepane – a crucial step towards its removal.

SRF launched the biotechnology company Revel Pharmaceuticals based on this work and previously published research on the synthesis of glucosepane.

Abstract

Although there is ample evidence that the advanced glycation end-product (AGE) glucosepane contributes to age-related morbidities and diabetic complications, the impact of glucosepane modifications on proteins has not been extensively explored due to the lack of sufficient analytical tools. Here, we report the development of the first polyclonal anti-glucosepane antibodies using a synthetic immunogen that contains the core bicyclic ring structure of glucosepane. We investigate the recognition properties of these antibodies through ELISAs involving an array of synthetic AGE derivatives and determine them to be both high-affinity and selective in binding glucosepane. We then employ these antibodies to image glucosepane in aging mouse retinae via immunohistochemistry. Our studies demonstrate for the first time accumulation of glucosepane within the retinal pigment epithelium, Bruch’s membrane, and choroid: all regions of the eye impacted by age-related macular degeneration. Co-localization studies further suggest that glucosepane colocalizes with lipofuscin, which has previously been associated with lysosomal dysfunction and has been implicated in the development of age-related macular degeneration, among other diseases. We believe that the anti-glucosepane antibodies described in this study will prove highly useful for examining the role of glycation in human health and disease.

Double Your Impact

A message from Herbie Hancock

Double your impact: donate for tomorrow - and today!

If you’ve been waiting for the right time to make a charitable donation to help end the diseases of aging, we’re here to tell you that now is that time!

Pandemic or no pandemic, degenerative aging relentlessly damages our bodies and those of our loved ones. But the terrible and selective toll of COVID-19 on older people has put the crippling effects of the aging process into stark relief, even for many who normally avoid thinking about aging or dreaming that something could be done about it.

COVID-19 mercilessly targets the vulnerabilities of the aging body. The disease exploits the waning power of the immune system to keep the virus from establishing a foothold and eliminate the infection if it starts. It continues on to ravage the aging body’s structural weaknesses (so-called “comorbidities”), lack of resilience, and loss of metabolic flexibility. Rejuvenating the body can not only thwart the chronic diseases that are driven by degenerative aging – it is the ultimate defense against future plagues as well.

Evidence to date suggests that rejuvenation biotechnologies targeting senescent cells can both protect the body against SARS-CoV-2 infection, and restore the youthful resilience of the body’s organs and tissues against COVID-19 if the virus takes hold. While most research to date has focused on senolytic drugs, our team at SENS Research Foundation are now working to restore and augment the aging immune system’s ability to eliminate senescent cells more physiologically. Natural killer cells (NK cells) are the main cell type involved in recognizing and extirpating senescent cells from our bodies. Dr. Amit Sharma and Elena Fulton have collected preliminary data at our Research Center showing that the proportion of NK cells that exhibit markers of strong cell-killing ability declines sharply with age. To confirm this preliminary finding, they will look for an age-related reduction in NK cells’ ability to kill senescent cells, using NK cells freshly isolated from young adult, middle-aged, and older people. They will run parallel tests on NK cells from the spleens of young (6 months) and old (24 months) mice.

Schematic: the age-dependent accumulation of senescent cells is in part due to impaired clearance of senescent cells by NK cells with age. Evidence suggests two factors are involved.

First, the fraction of NK cells with highly potent cell-killing function declines with age. Second, over time senescent cells lose the ligands that activate NK cells’ killing function, and begin to express ligands that signal to the NK cells that they are normal cells and should be left alone.

Developing interventions that target these two problems will allow us to enhance and rejuvenate our intrinsic senescent cell-killing ability, mitigating aging and age-associated diseases.

Moving from basic research to anti-aging intervention, the team is developing strategies to enhance senescent-cell-killing ability in old NK cells. They will test rejuvenation strategies including adoptive transfer of young human and mouse NK cells into aging mice, and agents that strip away the protective shielding that senescent cells throw up to defend themselves against NK cells. If transferring young NK cells works as a proof of concept, the team will move forward by adapting CAR-NK cell technology — a cutting-edge immune transfer biotechnology that is currently promising to revolutionize immunotherapy for some cancers at MD Anderson and elsewhere — to instead selectively target senescent cells.

By restoring and augmenting the body’s youthful ability to purge itself of dysfunctional senescent cells, these cells can be targeted without incurring the side-effects of destroying senescent cells when they’re playing their useful physiological roles in wound healing and regeneration, or the other potential toxicities of senolytic drugs (such as dangerous hits on platelets with Navitoclax).

So there is a double incentive to make a generous donation today: the potential to help end the diseases of aging, and the urgent object lesson of a global pandemic, which shows the potential of our research to make a difference against this or future plagues that will seek us out mercilessly if we continue to age as usual.

We urge you to support of SENS Research Foundation and the future of rejuvenation biotechnology by making a donation HERE!

Dr. Aubrey de Grey Awarded the 2020 Bacon Prize

We’re delighted to announce that SRF’s Chief Science Officer Dr. Aubrey de Grey has been awarded the 2020 Bacon Prize for Thought Leadership in Super Longevity at this year’s RAADfest.

The award was presented by James Strole Director of the Coalition for Radical Life Extension and glowing remarks about Aubrey’s career and life were made by Peter Diamandis, founder of the XPrize Foundation and cofounder of the Singularity University.

The Bacon Prize is awarded annually by the Coalition for Radical Life Extension to an individual in recognition of their excellence in work focused on curing aging, involving communication with both scientific and general audiences, and whose contributions have been documented and backed by peer review.

But Why "Bacon"?

The Bacon Prize is named for both Roger Bacon and Sir Francis Bacon (no relation!). Though they lived centuries apart, both men made pioneering contributions to addressing aging as a tractable medical problem.

Roger Bacon, a Franciscan friar born in the 13th century, was one of the earliest European proponents of the modern scientific method. His conviction in the value of experimental study – revolutionary at a time when much of natural philosophy relied on appeals to the presumed authority of Biblical or Classical sources – was inspired by his experience applying the empirical method of the Arabic polymath Ibn al-Haytham to observations and theories in texts attributed to Aristotle. Bacon found that many of his results differed from those that would have been predicted by the Greek philosopher, and so became an staunch advocate of the importance of gathering adequate data before drawing conclusions.

Roger Bacon’s statue in the Oxford University Museum of Natural History.
(Photo by Michael Reeve)

625px-Somer_Francis_Bacon

Portrait of Francis Bacon by Paul van Somer I.

Three centuries later the statesman Francis Bacon took those same concepts further, arguing that scientific knowledge could only reliably be acquired through logical reasoning based on the observation of natural phenomena. Most importantly, he emphasised the need for scientists to adopt a sceptical world view: accepting the truth of a hypothesis only once confident that any plausible alternative explanations were disproven. This attitude of caution – a crucial antidote to the innate tendency of humans to favour certain ideas for any of a host of irrational reasons – remains a cornerstone of scientific best practice into the present day.

The Bacons’ contributions to the fundamental process of scientific discovery certainly underpinned the development of modern science, and thus medicine – but of course, many other thinkers played roles in that paradigm shift. To understand why these two men in particular were selected to lend their name to a prize for research in averting the decline of aging requires a little more investigation of their work.

Aging as a Preventable Disease

Roger Bacon was one of the first thinkers to identify aging itself as a disease – and one whose course could be improved through health care. In his manuscript “The Cure of Old Age and Preservation of Youth,” he wrote that;

… you perhaps will maintain, that the whole have no need of a Physician, but they that are sick: But I may rejoin to the Saying, That your Health, I doubt, is in a Pharisaical condition; and when you have read this Book, I doubt not, but you will abate your Opinion. For, beside that Aptitude and Inclination to some Disease, which (though latent to you, yet manifest to a Physician) may be in you, from the very moment of your Nativity, you make every day a considerable step toward Old Age, which is itself a Disease…

I am persuaded, were men as careful in preserving their Health, as they are solicitous for the recovery of it, they might often multiply the Sum of their Years, and live the Product without a Disease. And I count it a Piece of Skill in a Physician far surpassing the most admirable Cures, to preserve a Man from all Diseases.

Repairing the Damage

Francis Bacon similarly advocated for healthy longevity, and indeed presaged the modern concept of rejuvenation through the repair of age-related damage for which Dr. de Grey has become so well-known, in his work “The Historie of Life and Death (With Observations Natural and Experimental for the Prolonging of Life.)

Ancient is the saying and complaint, that Life is short, and Art long. Therefore our labours intending to perfect Arts, should… consider by what means the Life of man may be prolonged. For long life… should not be despised, because it affords longer opportunity of doing good Works. … the happiness of long life is naturally desired, although the means to attain it, through false opinions and vain reports be hard to find…

That which admits reparation, remaining whole and sound in Essence, may be eternally preserved… for young living creatures being all over and wholly repaired, do by their increasing in quantity, and growing better in quality, show that if the measure and manner of repairing decayed not, the matter of repairing might be eternal.

A Letter to the Economist

To the Editors:

Your special report highlighted the growing number of people suffering dementia as one of the many terrible effects of an aging world. It did not consider the potential of medical intervention into aging itself to mitigate that future. Like all forms of age-related ill-health, dementia is caused by the accumulation of cellular and molecular damage in our tissues with age. We at SENS Research Foundation develop therapies to remove and repair this damage, so as to postpone (eventually indefinitely) age-related disease and debility, including neurodegenerative aging diseases such as Alzheimer’s disease (AD).

One such therapy is maintenance of the brain’s neurons. A key subpopulation of these cells is selectively lost in AD, and a strategy to replace these and other neurons lost to aging processes is essential to maintaining cognitive function.

Only recently have scientists established methods to reliably transplant neuronal precursor cells into the brain in ways that allow them to integrate into and function within existing synaptic networks. Unfortunately, the transplant procedures are laborious and invasive and cannot scale to reach all the affected areas of the brain.

We sponsor work in this area by Dr. Jean Hébert of Albert Einstein College of Medicine. Dr. Hébert has developed a new strategy to overcome this problem using microglia, a non-neuronal brain cell type capable of dispersing extensively throughout the brain upon implantation if a favorable space is made. By engineering microglia to transform into neurons upon administration of a drug, and using another drug strategy to create favorable space for them across the brain, Dr. Hébert proposes to deliver working neurons all across the aging brain, allowing the continuing replacement of neurons lost to AD, to trauma, and to other aging processes.

Jim O’Neill, CEO

Mask Competition

The SRF Design-a-Mask Competition!

Mask Up With SRF

Throughout the COVID-19 pandemic, SENS Research Foundation’s team at our Research Center in Mountain View have continued to work as intensively as local regulations permit. Of course, that includes the mandatory use of face coverings.

We invited all our supporters to submit designs for an official SRF mask. As well as being worn by our staff, these masks will be available in limited supply to anyone who’d like to  support our work to end age-related disease and disability.

At the close of the competition, we’ll select the best three entries and run a poll on SRF’s Facebook Page to allow our supporters to vote for their favourite design.

The Importance of Masks

It’s widely agreed that wearing a mask reduces your chances of transmitting SARS-CoV-2 to others, even during the critical period of “silent spread,” when you have no symptoms and are most likely to transmit the virus to your friends and neighbors.

There’s now a growing body of evidence that wearing a mask also protects you from becoming infected, as well as evidence (reviewed in a recent article from the New England Journal of Medicine) that individuals who are infected despite wearing a mask are still several times less likely to develop severe illness. This may be because face coverings significantly reduce the initial dose of the virus received, giving the body more time to mount a response before things get out of hand.

Competition Rules

  1. The competition has now ended. Please see below for pre-ordering an SRF mask.
  2. All entries must comply with the following specifications:
    • Entries must be final designs and printable.
    • Use the design template to ensure proper sizing.
    • Vector graphics are strongly preferred.
    • Any raster graphics must be 300 dpi or higher.
    • Files should be in PDF, TIFF, PSD, IDML, EPS, or AI format.
    • Files should be submitted HERE.
  3. The design submitted must be relevant to SENS and/or rejuvenation biotechnology.
  4. All submitted work must be the original work of the entrant(s) and must not include, be based on, or derived from any pre-existing or third-party designs, trademarks, or copyrighted images.
  5. All entries will become the property of SENS Foundation, Inc. By submitting an entry, each entrant agrees that any and all intellectual property rights in the logo design are deemed assigned to SENS Foundation, Inc.
  6. Selection criteria:
    1. Relevance.
    2. Originality.

For questions, please contact [email protected].

Mask Availability

Our masks will be produced shortly after the selection of the winning design, and will be available through the end of 2020 – while supplies last.

If you’d like to secure an official SRF mask for yourself, you can pre-order by making a donation through the PayPal links below at any time before the final winner is announced.

Revel Strengthens Boards

SRF spin-off Revel Pharmaceuticals, a privately held biotechnology company creating therapeutics to reverse and repair damage that results from aging – particularly extracellular crosslinks – has announced recent additions to its Board of Directors and Scientific Advisory Board.

Joining as a member of the Board of Directors is Jennifer Cochran, Ph.D. and joining as a member of the Scientific Advisory Board is Vincent Monnier, Ph.D. “We are thrilled to attract stellar leadership that matches the level of promise of Revel’s mission of attacking diseases of aging,” said Aaron Cravens, Revel co-founder and CEO.

For more information, read the full announcement on Revel’s site.

Defatting the Streaks

Image from "Affinity-Driven Design of Cargo-Switching Nanoparticles to Leverage a Cholesterol-Rich Microenvironment for Atherosclerosis Therapy"

The removal of damaged material from within atherosclerotic plaques (“fatty streaks”) to restore cardiovascular health is a key component of SENS, now being developed for the clinic by SRF ally Underdog Pharmaceuticals. Exciting new preclinical results from another group using this strategy have recently been published in ACS Nano.

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