Executive Summary, Investigative Report

To Our SENS Research Foundation Community,

In June 2021, the SENS Research Foundation began an outside investigation into the conduct of our Co-Founder and then-Chief Science Officer Dr. Aubrey de Grey. We initially began the investigation after we learned of allegations of inappropriate conduct concerning Dr. de Grey from two members of the scientific community – allegations we took to heart as a person-centered nonprofit organization. The Foundation appointed an independent investigator, Sue Ann Van Dermyden of Van Dermyden Makus, to look into the allegations. Recently, Ms. Van Dermyden reported to the SENS Board of Directors on her findings.

In the spirit of transparency and accountability, we are making available an Executive Summary report of the investigation’s outcomes, prepared by Ms. Van Dermyden, that substantiates many of the concerns of boundary-crossing behavior initially raised by the complainants. You can access the report by visiting: https://www.sens.org/executive-summary-investigative-report/. Out of respect for the complainants, our investigator has refrained from including their identifiable information in this public-facing report.

Since we first announced the investigation, the scope of Ms. Van Dermyden’s work in this investigation had expanded. In August 2021, we learned of allegations that Dr. de Grey had attempted to exert influence over one of the complainants – an action that ultimately led to Dr. de Grey’s separation from SRF. You will find that Ms. Van Dermyden’s assessment affirms that Dr. de Grey improperly attempted to exert influence over one of his complainants. Also, as Ms. Van Dermyden notes in her report, her firm is continuing to look into allegations brought forward by other women, though it would be premature to speculate on the outcomes of that effort.

At SENS Research Foundation, we expect our colleagues to adhere to the highest levels of integrity, not only in carrying out the organization’s vitally important mission, but in how they conduct themselves in personal interactions as well. The behavior detailed within this report is simply unacceptable. On behalf of the SENS Research Foundation, we, the Foundation’s Directors, extend our heartfelt apologies to the individuals subjected to this behavior, as well as our gratitude for their bravery in coming forward.

We also want to extend our deep gratitude to the Foundation’s employees and partners, who have remained focused on our life-sustaining mission in spite of a recent, regrettable period of disruption and distraction. You are the Foundation’s lifeblood, and we are here to support you and amplify your work.

Success in the fight against aging demands collaboration and partnership. It demands integrity. It demands relationships rooted in mutual respect. As leaders in the field, we take seriously our responsibility to set a tone for the longevity industry. We hope this investigation demonstrates our deep commitment to these values.

Onward,
The SENS Research Foundation Board of Directors

To read the full Executive Summary of Investigative Findings, click this link.

To view the accompanying Exhibits to the Executive Summary, click this link.

Hyperbolic Hyperbaric “Age Reversal”

Lower-quality, clickbait-hungry media outlets love sensationalist claims, but one does expect better from the public relations department of an internationally-respected research university. And it was an easy jump from the already-overstated “In First, Aging Stopped in Humans” and “treatments can reverse two processes associated with aging and its illnesses” to saying that a treatment “can reverse aging process” — and to then land in a mud-pit of self-parody with “Human ageing reversed in ‘Holy Grail’ study, scientists say.”

The actual findings of a recent study on hyperbaric oxygen treatment (HBOT) were much more limited. Despite some intriguing indicators, the actual impact of HBOT on aging based on this study is entirely unclear, quite plausibly negligible, and in any case objectively less impressive than that of (say) regular exercise, which certainly does not “reverse aging.”

Originally developed to treat divers with decompression sickness or dangerous nitrogen bubbles in their blood after surfacing too quickly, HBOT involves administering 100% oxygen to subjects resting in a chamber where the atmospheric pressure is artificially elevated. This enhances the dissolution of oxygen directly into the plasma (normally, it’s almost entirely carried in the red blood cells), and the dissolved oxygen in turn drives out the nitrogen, while delivering more oxygen to the tissues. Later, it was found that repeatedly subjecting people or experimental animals to HBOT can cause an adaptive response that paradoxically resembles being subjected to inadequate oxygen (hypoxia) — a phenomenon referred to as the hyperoxic-hypoxic paradox.

Under the relatively loose 510(k) regulations for medical devices in the United States (standards that were modified over 2019-2020 to still-unclear effect), HBOT devices are also “cleared” (but not approved) for carbon monoxide poisoning and a surprising range of other indications, including treatment of chronic wounds and necrotizing soft tissue infections, burn or crush injuries, and unexplained sudden sensorineural hearing loss. Regulation of medical devices is similarly inadequate internationally. Some clinicians also administer HBOT to patients with post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI), although the evidence base for these uses is weak. Device manufacturers and clinics sometimes push the line even further, advertising their HBOT devices and services for yet more speculative indications, resulting in FDA warnings to consumers and the occasional reprimand to manufacturers, although enforcement is hampered by a trend in the courts to recognize broad commercial freedom of speech rights.

So what about HBOT for aging?

The Study Setup

The study recruited 35 independent-living men in good functional and cognitive condition (granted the effects of aging — they were age 64 and older, with some in their early 80s) and had them complete a baseline assessment. They lost five participants right there — a problem that gets compounded as the study goes along, as we’ll see. The remaining thirty subjects underwent 90-minute HBOT sessions five days a week over the course of three months, for a total of 60 sessions. Whole blood samples were taken at the beginning of the study, at the midway point, and after the last session, followed by one last blood test a week or two after their last HBOT session. When the samples were viable, scientists tested the lengths of the subjects’ blood cell telomeres (the now-famous “shoestring nibs” on the ends of our chromosomes that keep them from unravelling after multiple cell divisions), as well as looking for what they characterize as “senescent” T-cells. This is where the attrition problems started to get worse. After five of the initial recruits failed to complete their baseline survey, only 30 people remained to contribute samples — and of those, the researchers had to throw out four patients’ telomere analyses and ten patients’ “senescent” T-cell analyses, either because the samples contained too few cells to analyze, or because of lab technician errors. As such, the stated findings are based on very few data points indeed. And aside from reducing the statistical power to attribute (or not) any changes observed to random chance, counting only those data points may also have actively skewed the results. People who don’t complete a study or whose biological samples are not measurable could reflect real differences in the people who finish a trial versus those that began it: for instance, participants providing viable samples may have had unusually robust blood cells for their age, while those who completed baseline surveys may have been more conscientious (thus more inclined toward healthy lifestyle practices) than average. Because of this potential source of bias, the accepted way to analyze a human clinical study is a so-called intention-to-treat analysis (ITT), in which you use all of the data from all of the subjects whether they actually finished the study (or gave viable samples) or not. Instead, in this case, they just ignored all the people who didn’t complete their initial assessment (that actually is sometimes acceptable, even in ITT), and also performed their analyses only on the people whose samples were all viable. To put it in fewer words, the researchers only compared people who started to the same people if they finished. Yet those who finished are skewed away from the whole group of those who started the study in the first place. Moreover, with no control group of any kind, we don’t know what would have happened anyway to another group of similarly-situated people who spent time under a kind of “placebo HBOT,” such as subjecting them to only very mild increases in atmospheric pressure, breathing something closer to atmospheric air (as). So, all right: the meal comes with a cartoonishly-large pillar of salt on the side. But with all those caveats, what did they say they found? After completing the protocol plus a two-week recovery period, telomere lengths in viable samples across several populations of immune cells “increased significantly by over 20% following HBOT,” and “There was a significant decrease in the number of senescent T-helpers by -37.30%±33.04 post-HBOT (P<0.0001)” while “T-cytotoxic senescent cell percentages decreased significantly by -10.96%±12.59 (p=0.0004)”. Is that actually what they found? And suppose that they had shown that (and shown it convincingly): would that be enough to justify a claim of having “stopped” or even “reversed aging”?

Tee-Tottering Telomeres

Let’s first look at the reported change in telomere length. It’s true that, when you look at a large population of people, longer blood cell telomeres and slower blood cell telomere shortening tend to correlate with poorer health outcomes. But that doesn’t make blood cell telomere length even a good proxy for current biological age at the individual level — let alone a causal driver of aging..

First, although blood cell telomere lengths do overall shrink over the course of multi-year periods when you look at aggregated data from an entire population of people, individuals’ telomere lengths swing wildly up and down over the course of mere months — that is, over lengths of time that include the entire duration of the HBOT study. So testing individual subjects’ telomere lengths as a measure of their individual biological age, and then testing again just a couple of months later, guarantees results that are corrupted by lot of sheer noise — and remember, just 24 subjects even had results the lab could read in the first place.

In fact, up to a third of individuals tracked show stable or even increased telomere lengths in their blood cells when re-tested as much as a decade later, due to a mixture of what are presumed to be real changes and lab artifacts. Obviously, degenerative aging is not being arrested or even massively reversed in one person in three across the population every ten years: imagine what an exciting breakthrough it would be to make that happen! So we know from that alone that we can’t use individual people’s blood cell telomere lengths as reliable indicators of age-related change, even over the course of a ten-year period. We therefore can’t possibly take a similar claim for HBOT seriously if it’s based on the same measure taken from 24 people over the course of mere months.

Moreover, although blood cell telomere length does correlate with telomere length in some tissues, the correlation is pretty weak, ranging from explaining 2% of the variation in the testes to a maximum of 14% in one peripheral nerve — and it has no correlation at all to the telomere lengths of about one-third of our tissues! Whatever blood cell telomere length tells us about health, in other words, it’s a pretty lousy proxy for whatever role telomere length plays in aging across the body as a whole.

Worse: calendar age itself — the most important determinant of biological age, which is what advocates want to use blood cell telomere length to measure — explained just 3.3% of the person-to-person variability in telomere length when all tissues were taken into account, and such important contributors to accelerating aging such as body mass index (BMI, as a proxy for obesity) and smoking status explained less than 1% of variation. And African Americans’ telomere lengths are longer than those of Americans of European descent in in nearly all tissues — a result consistent with multiple previous studies looking at blood cell telomere lengths. Yet we know that African Americans suffer with a higher burden of age-related disease and shorter life expectancies than white or Asian Americans. If we’re looking for a measure of biological aging, it makes little sense to use a metric that bears so little relationship to key predictors of future ill-health and death.

The weakness of telomere length as a biomarker of aging becomes clearer when you compare it to more robust markers, such as epigenetic aging clocks or algorithmic scores calculated mostly from common blood blood-test markers. In a comparative study, eleven candidate biomarkers of aging were compared to see how closely they would reflect the impact of aging on a group of older people in the domains of physical functioning (measured on tests of things like balance, grip strength, and motor coordination), rate of cognitive decline, and subjective signs of aging such as having an “old” face. One of the composite scores and one of the early iterations of an epigenetic aging clock consistently correlated with these age-related outcomes (albeit quite modestly in both cases), but telomere length failed to correlate with any of them. Similarly, telomere length was not associated with current health status in a cohort of 50-something New Zealanders, as measured on the  SF-36 evaluation of health status.

And those first-generation epigenetic aging clocks are far inferior as predictors of future age-related morbidity and mortality than more recent iterations such as GrimAge and DNAm PhenoAge, as well as non-epigenetic biomarker composites such as the PhenoAge blood test composite score against which DNAmPhenoAge itself was trained up by machine learning. Indeed, a comparison study of aging Swedes found that eight out of nine different biological age scores predicted risk of death over the next twenty years beyond the predictive power of calendar age itself. Telomere length was the odd man out, being the only one that failed to add value to knowing a subject’s calendar age.

So that’s telomere length. What about the reduction in “senescent” T-cells?

There’s “Senescence” … and then there’s Senescence

Anyone who’s been following research on senescent cells and their roles in diseases of aging and age-related ill-health — and on the sweeping rejuvenation effects of triggering those cells to self-destruct with “senolytic” drugs — will be excited by the authors’ conclusion that their “study indicates that HBOT may induce significant senolytic effects” and “suggests a non-pharmacological method, clinically available with well-established safety profile, for senescent cells populations decrease.” But does the study actually support that claim?

The first thing to understand is that despite the fact that it’s standard terminology in the immunology world, “senescent” T-cells aren’t actually “senescent cells” in the sense usually used in the geroscience world. (And no, they aren’t anergic T-cells either, though the two do show some overlap). True senescent cells are in a state of total growth arrest, unable to make new copies of themselves due to an interlocking set of pathways of regulation. By contrast, “senescent” T-cells’ ability to proliferate is reduced, but still fundamentally intact. Additionally, the reasons for “senescent” T-cells’ short telomeres and reduced replicative ability are quite different from those of true senescent cells. T-cells are normally very “trigger-happy” with their telomere-lengthening telomerase enzyme (and possibly use another telomere-lengthening mechanism as well), which allows them to quickly replicate when they encounter a known target and flood the zone with new T-cells. “Senescent” T-cells’ telomere-lengthening activity is sluggish compared to normal T-cells because an energy-sensing pathway tunes down its access to the enzyme. By contrast, true senescent cells actively enforce a state of total growth arrest, using an interlocking set of cellular pathways that are just not active in normal cells, in order to prevent the replication of damaged, often cancer-prone cells.

In short, jumping from post-HBOT reductions in the number of these “senescent” T-cells to potential effects on classical senescent cells is really just a misunderstanding of what kinds of cells are involved in each case.

OK, you say, but still, these so-called senescent T-cells are bad, aren’t they? So getting rid of them must be good — right? Well, maybe (though no one has demonstrated that yet). But did HBOT actually get rid of them in the first place?

The first problem here is that we don’t even know for sure that the researchers were measuring “senescent” T-cells to begin with! T-cells are judged “senescent” based on blunted replicative ability, lack of the marker protein CD28 on their surface, and the abnormal presence of the marker CD57 — but the investigators here were only able to measure CD28, and therefore were judging T-cells “senescent” without actually using the full criteria to test for them. So whether there was even a change in “senescent” T-cells in the first place is quite uncertain. (The same goes, in fact, for natural killer (NK) cells, which are another kind of immune cells. Mature NK cells test negative for the marker CD3 but positive for the marker CD56 — but these investigators tested for cells positive for both markers! Maybe this was just a typo that got repeated throughout the manuscript, but as it stands, it can only further fuel uncertainty around the results as a whole).

Add to that the fact that a mere reduction in the numbers of measured cells doesn’t prove that HBOT destroyed them. Maybe HBOT somehow triggered this group of cells to adopt a different functional status. Or maybe the cells (or a subset of them) retreated back to their reservoirs in the lymph nodes, since the researchers were only sampling them in peripheral blood. Who knows?

What we certainly don’t know is that HBOT treatment destroyed these cells in substantial numbers — and again, even if it did, it would be unclear what the researchers had done, since they didn’t actually fully characterize these as “senescent” T-cells in the first place, and they got the result from just twenty samples (after throwing out ten unusable results) — all in a study with no control group.

“Aging Reversed”?

So in short, the actual details of the study show that even the narrow claims of the study abstract aren’t fully justified. It’s not clear that blood-cell telomeres were lengthened any more than they would have been without HBOT; it’s not clear that “senescent” T-cells were reduced in numbers, let alone actually destroyed; and if “senescent” T-cells had been destroyed, it would not demonstrate a senolytic effect of HBOT, because “those aren’t the ‘senescent’ cells you’re looking for.”

And even if the study had robustly demonstrated that every one of the points above really did occur, it would not constitute “reversing aging” — or even justify the more restrained claims that “blood cells actually grow younger as the treatments progress” or “that the aging process can in fact be reversed at the basic cellular-molecular level.”

Aging Reversed!

The mission of SENS Research Foundation is to accelerate the development of rejuvenation biotechnologies: new therapies that remove, repair, replace, and render harmless the real cellular and molecular damage of aging. Scientific studies have rigorously demonstrated that these proposed therapies can remove or repair members of the various categories of cellular and molecular aging damage in animal models — and in an increasing number of cases, in human clinical trials.

When we say that we aim to “reverse aging,” we actually mean reverse aging: not just that damaged cells and molecules will be removed and replaced, but that health and function will be restored — something the HBOT study did not even attempt to demonstrate. Bona fide rejuvenation can be seen (for example) in aging animals treated with senolytic drugs, and in humans with Parkinson’s disease given even the crude early forms of neuronal replacement therapy (and the first glimpses of its next generation).

Going forward, proof-of-concept studies at our Research Center and in expert labs funded by the Foundation will demonstrate more and more rejuvenation biotechnologies. The emerging rejuvenation biotechnology industry will continue to flourish, advance promising breakthroughs into human trials, and eventually license treatments for clinical use (first in the most at-risk, and increasingly in the otherwise-healthy aging). In a future we can see through a glass darkly, our vision will be revealed: a new humanity, open to an indefinite future free of the specter of decline. That day, we will see aging reversed.

PulseChain Airdrop

PulseChain Airdrop has ended!

The Sacrifice Phase for the Airdrop is officially closed and all final donor information has been sent to the PulseChain team. NO changes or additions can be made at this time.

The PulseChain Airdrop has ended!

The PulseChain Airdrop sacrifice phase has ended. We are extremely grateful to Richard Heart and the over 2,000 donors who supported our mission. 

We will be announcing the total raised as we finish processing the donations.

Please refer to the FAQs below and send us an email at [email protected] if your question was not answered. If you have questions or concerns on how the Airdrop will occur, please contact the Pulse team directly through PulseChain.com and/or any other of their available channels of communication like Twitter: @RichardHeartWinRichard Heart’s YouTube channelPulseChain Telegram Group. SRF’s portion of the Airdrop is completed.

After a very intense (and exciting) month of emails, donations, and data processing, we will now go back to working tirelessly to end the ill-health and suffering of aging! The progress we will make thanks to your generous support is incalculable! From all of us, thank you.

PulseChain Airdrop FAQs:

NO, the Sacrifice Phase has ended and any further donations will not be entered into the Pulsechain Airdrop. However, if you want to donate to SRF because you believe in our mission as much as we do, you can go to www.sens.org/donate to make a donation and receive a tax benefit.

SENS Research Foundation is a separate entity from the PulseChain, we are a scientific nonprofit organization that Richard chose to support through his Airdrop. 

We cannot advise you on anything that has to do with their process and/or Pulse reward. Please contact the Pulse team for more information.

Depending on if you followed the PulseChain process correctly, you should still be participating in the Airdrop. However, because you sent your currency directly to the PulseChain and not to SRF, SRF cannot verify or confirm your ‘sacrifice‘.

Please contact the Pulse team if you require further information.

We go by the day that donations came in as shown by the financial institution used to process them. Our time zone is Pacific Standard Time. We are only sending DATES, not times, of donation for the Airdrop.

To receive a tax exempt receipt from SRF, you must 1) be a resident of the United States of America, and 2) send your full name to SRF for recording. You can send your full name anytime within the next two months to receive your donation receipt as long as you can produce your confirmation email for verification. You can expect your donation receipt, by email, before the end of November.

If you donated to SENS Foundation Europe, you will need to communicate with them at [email protected] for a tax receipt. If you donated to Aging Research Network, please contact them at [email protected].

We are only sending dates, USD values, and wallet addresses to the Pulse team – no names or email addresses will be sent outside of SRF. If you did not provide a full name for a donation receipt, you will be marked as “Anonymous” in our accounting system and no further action needs to be taken.

Most likely, yes. Your donation will be sent to the Pulse team with the date you MADE the donation. If that date is proven to be prior to the end of the Sacrifice stage, you will still qualify for the Airdrop.

If we can verify that your donation was made during the Sacrifice phase, you were allowed 14 extra days from the day the Sacrifice Phase ended to communicate with us and fill out the form.

The 14 day grace period ended on August 16. At this time all final donor information has been sent to the PulseChain team and NO changes or additions can be made.

No, in order for you to get a tax exempt receipt from us while donating from Europe you needed to either have donated to our SENS EU office in the UK, or used a partner from the TGE https://www.transnationalgiving.eu

No, in order for you to get a tax exempt receipt from us while donating from Canada you needed to have donated to our partner Aging Research Network.

These are the original instructions from our PulseChain Airdrop page:

Please do not make your donation until you have read ALL of the instructions below and sent all of the required information. To make this easy, you can click HERE for a form to fill out with the required information – but it is critical that you first read the instructions below.

You can donate to SRF in any currency, including any cryptocurrency that is traded at Coinbase (note that, in particular, this means we cannot accept HEX or XRP). Check our DONATE page for all the methods of donation that we accept: We can only verify crypto donations sent to our wallet addresses listed on our webpage. There is no minimum donation threshold that must be met.

If it’s a crypto currency, it will have to be a coin that we accept – any coin that Coinbase trades – and our addresses are listed on our donation page cited above. To verify that your donation is yours, we are asking that you either send a source address (if it’s from a non-custodial wallet), or (if your wallet is on an exchange) we ask that you create a random 3 digit number that your crypto donation must end in. You will document this number on the form. * WE NEED THIS INFORMATION BEFORE YOU MAKE YOUR DONATION.

You may want to send an email to [email protected] right after you make your donation – this isn’t required but will speed up how fast we can confirm your donation.*

Once your donation is processed, we’ll send you a confirmation email that will include your date of donation, its USD value, and your provided ETH wallet address within 48 hours of your donation. If this is correct, you have no further actions to take. If it is incorrect, you have 24 hours to correct any errors. After that, we will send that exact information to Richard Heart to finalize your entry into the Airdrop. Don’t worry, the actual date of your donation is the date that will be sent to Richard Heart, regardless of when we get the information to him.

Please be aware that the address you send for receipt of reward MUST have a private key associated with the address – i.e. exchanges will not work for acquiring the donation reward, it must be a decentralized or non-custodial wallet. To be clear, DO NOT SEND US YOUR PRIVATE KEY. You simply must have one on your wallet to be able to claim your reward.If you are donating in a fiat currency, we can give you our bank information or you can send a check to our address in Mountain View or use a credit card with Paypal ([email protected]). We also accept stock donations into our TD Ameritrade Account.

If you are a UK citizen and would like a tax benefit, please reach out to [email protected] to arrange your donation with SENS Foundation Europe (SENS EU). They can accept crypto and fiat donations. You’ll need to send your donation receipt from SENS EU and ETH wallet address to [email protected] to enroll in the Airdrop.*

If you are a Canadian citizen and would like a tax benefit, please fill out and follow the instructions on this form to make a donation to Aging Research Network (ARN), a Canadian Charity aligned with SENS Research Foundation that Richard Heart has agreed to accept receipts from for the Pulse Airdrop. After you make your donation and receive your receipt from ARN, forward that receipt and your ether wallet address to [email protected].

Their representative Kevin will be in touch shortly. Be aware that Aging Research Network can only accept fiat donations.

Any donation we cannot verify will not be entered into the Airdrop, so please fill out this form carefully.

Any further details you need regarding the reward phase of the Airdrop, please direct to Richard Heart’s team as we are not involved with that phase.

Thank you for your support! Donors like Richard Heart, and yourself, keep SRF doing the important work to treat and cure diseases of aging. We are immensely grateful.

Live long. Live healthy.

THE SACRIFICE PHASE IS LIVE

We need you to read these instructions first!

Donors have been making costly errors that we cannot fix – please follow these instructions and make sure your donation reaches SRF.

*If you are having difficulty emailing us at [email protected], please email us at [email protected].

Please do not make your donation until you have read ALL of the instructions below and sent all of the required information. To make this easy, you can click HERE for a form to fill out with the required information – but it is critical that you first read the instructions below.

You can donate to SRF in any currency, including any cryptocurrency that is traded at Coinbase (note that, in particular, this means we cannot accept HEX or XRP). Check our DONATE page for all the methods of donation that we accept: We can only verify crypto donations sent to our wallet addresses listed on our webpage. There is no minimum donation threshold that must be met.

If it’s a crypto currency, it will have to be a coin that we accept – any coin that Coinbase trades – and our addresses are listed on our donation page cited above. To verify that your donation is yours, we are asking that you either send a source address (if it’s from a non-custodial wallet), or (if your wallet is on an exchange) we ask that you create a random 3 digit number that your crypto donation must end in. You will document this number on the form. * WE NEED THIS INFORMATION BEFORE YOU MAKE YOUR DONATION.

You may want to send an email to [email protected] right after you make your donation – this isn’t required but will speed up how fast we can confirm your donation.*

Once your donation is processed, we’ll send you a confirmation email that will include your date of donation, its USD value, and your provided ETH wallet address within 48 hours of your donation. If this is correct, you have no further actions to take. If it is incorrect, you have 24 hours to correct any errors. After that, we will send that exact information to Richard Heart to finalize your entry into the Airdrop. Don’t worry, the actual date of your donation is the date that will be sent to Richard Heart, regardless of when we get the information to him.

Please be aware that the address you send for receipt of reward MUST have a private key associated with the address – i.e. exchanges will not work for acquiring the donation reward, it must be a decentralized or non-custodial wallet. To be clear, DO NOT SEND US YOUR PRIVATE KEY. You simply must have one on your wallet to be able to claim your reward.If you are donating in a fiat currency, we can give you our bank information or you can send a check to our address in Mountain View or use a credit card with Paypal ([email protected]). We also accept stock donations into our TD Ameritrade Account.

If you are a UK citizen and would like a tax benefit, please reach out to [email protected] to arrange your donation with SENS Foundation Europe (SENS EU). They can accept crypto and fiat donations. You’ll need to send your donation receipt from SENS EU and ETH wallet address to [email protected] to enroll in the Airdrop.*

If you are a Canadian citizen and would like a tax benefit, please fill out and follow the instructions on this form to make a donation to Aging Research Network (ARN), a Canadian Charity aligned with SENS Research Foundation that Richard Heart has agreed to accept receipts from for the Pulse Airdrop. After you make your donation and receive your receipt from ARN, forward that receipt and your ether wallet address to [email protected].

Their representative Kevin will be in touch shortly. Be aware that Aging Research Network can only accept fiat donations.

Any donation we cannot verify will not be entered into the Airdrop, so please fill out this form carefully.

Any further details you need regarding the reward phase of the Airdrop, please direct to Richard Heart’s team as we are not involved with that phase.

Thank you for your support! Donors like Richard Heart, and yourself, keep SRF doing the important work to treat and cure diseases of aging. We are immensely grateful.

Live long. Live healthy.

What is the Pulse Chain Airdrop?
Cryptocurrency HEX founder Richard Heart is creating a new currency, Pulse. Prior to the launch of this new cryptocurrency, Richard is doing an Airdrop – giving away some Pulse.

How is SRF involved?
Richard is a long-time supporter of SRF and is asking that people “sacrifice”, or make a donation, to SRF during the sacrifice phase. Making a donation to SRF will enter you into the Airdrop and a chance to earn Pulse when it launches, free of charge. Note that you should NOT make the donation until we notify you that the sacrifice phase has begun, but you should notify us of your intent to donate (see below).

Does the donation have to be in cryptocurrency?
No! That’s the best part. You can donate ANY currency: crypto, credit, stock, fiat. We will liquidate it for its USD value and communicate that donation value to Richard along with the Ethereum wallet address you provide to us.

Is this donation still tax deductible?
SRF is a 501(c)(3) non-profit in the United States, so any donation made to SRF should be tax deductible in America and you will receive a tax receipt for your donation – but please consult with your tax advisor. If you are in the UK, Canada, or some countries in mainland Europe, your donation can also be tax deductible. Please see below for further instructions.

Still interested?
Below are the guidelines for participating in the Airdrop. Please make sure you read through all of the instructions prior to participation.

General Rules

Prior to donation, please send your Ethereum wallet address to [email protected] along with any details you can share regarding your donation. If you have already done this, you are all set! No need to send another email.

You may want to tell us:

  • What currency you are donating in
  • How much of that currency
  • When you will be sending the donation
  • Your full name (optional, but possibly required for a donation receipt – check with your tax advisor)
  • Any of the verification information required below

You can donate to SRF in any currency. Check the Donate page for the methods of donation that we accept. There is no minimum donation threshold that must be met. Every dollar counts.

If you are donating a cryptocurrency, it will have to be a coin that we accept – any coin that Coinbase trades – and our addresses are listed on our donation page cited above.

For verification purposes:

  • If the wallet that is SENDING crypto is decentralized (such as a MetaMask or Trust wallet) and therefore NOT on an exchange, please send the wallet address.
  • If the wallet that is SENDING crypto IS on an exchange (such as Coinbase or Binance) we must give you a random number that your crypto donation must contain as you will not be able to send a source address.

The Ethereum wallet address you send for receipt of reward must have a private key – i.e. exchanges will not work for acquiring the donation reward. To be clear, do NOT send us your private key. You simply must have one on your wallet to be able to claim your reward.

Richard Heart suggests MetaMask – which is a phone-friendly and easy to use decentralized crypto wallet.

If you are donating in a fiat currency, we can give you bank information, or you can:

  • use a credit card with Paypal,
  • send stock or bonds to our TD Ameritrade account, or
  • mail a check to our Research Center at the address below:

SENS Research Foundation, Inc.
ATTN: Airdrop
110 Pioneer Way, Ste. J
Mountain View, CA 94041
USA

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Lipofuscin Degradation by Bacterial Hydrolases

German Institute of Human Nutrition

Principal Investigator: Tilman Grune
Research Team: Annett Braune, Annika Höhn, Tim Baldesperger

Prof. Grune is the Scientific Director of the German Institute of Human Nutrition and has been working on protein degradation of damaged proteins and aging.

Lipofuscin (LF) is a strongly oxidized material composed of covalently cross-linked proteins, lipids, and carbohydrates. Cellular LF increases with age and negatively correlates with the remaining life span of cells. Lipofuscin accumulation is especially pronounced in postmitotic cells (including cardiomyocytes and neurons) as these cells are unable to “dilute” their lipofuscin via cell division. LF by itself impairs cardiomyocyte function by declining its contractility. Importantly, no known mammalian enzyme degrades lipofuscin, therefore LF accumulates within the cell, mostly within the lysosomes.

Microorganisms, particularly bacteria, possess a wide array of enzymes that allow the degradation of any conceivable molecule formed in nature. The project, therefore, aims at identifying bacterial enzymes able to degrade LF. The project includes the following tasks:

  • isolation of human LF and identification of its components,
  • identification of microbial hydrolases able to degrade LF, and
  • testing the effect of identified hydrolases and their products in living cardiomyocytes.

Research Highlights:

Prof. Grune has previously studied the role of lipofuscin in proteasomal inhibition in human cell culture models using artificial lipofuscin. Later, he worked with isolated lipofuscin from human retinal epithelial cells and described the effects of this material on microglial cells. After securing a reliable source of human hearts, the Grune team began isolating real tissue lipofuscin. They are presently working to analyze composition and quantify degradation of LF.  In recent years, the team has also worked with “artificial” lipofuscin and shown in a preliminary experiment that degradation by bacterial enzymes is possible. Upgrades to primary human material will allow optimization of the process of identifying bacterial enzymes with the ability to degrade the material.

Catalyzing Degradation of Tau Aggregates

  • Research Info
  • Team Members
  • Publications
  • Photos
  • Funding
  • Research Info
  • Team Members
  • Publications
  • Photos
  • Funding

Tau is the major microtubule-associated protein (MAP) in mature neurons in the central nervous system. The MAPT (microtubule-associated protein tau) gene encodes for six splice variants that are highly soluble; their main function is interacting and stabilizing microtubules, along with other MAPs. The ability of tau to stabilize the microtubule is aided by its phosphorylation.

Hyperphosphorylation of tau depresses its biological activity and can lead to destabilization of microtubules. Also, hyperphosphorylation of tau proteins can cause it to aggregate into oligomers, which in turn assemble into helical and straight insoluble filaments and ultimately mature into neurofibrillary tangles (NFTs).

In Alzheimer’s disease brain, tau is three to four-fold more hyperphosphorylated than in the normal adult brain, leading to a pathological buildup of NFTs. The accumulation of NFTs comprising hyperphosphorylated tau is also observed in normal aging (PMID: 24548606).

Various other neurodegenerative diseases, collectively called tauopathies – including Pick’s disease, corticobasal degeneration, progressive supranuclear palsy, frontotemporal lobar dementia with Parkinsonism linked to chromosome 17 (FTDP-17), and dementia pugilistica – are also caused by tau aggregation.

In consultation with SRF-supported biotech company Covalent Bioscience, SENS Research Foundation has initiated a project to develop a novel way to remove abnormally aggregated tau as a therapeutic intervention with potential relevance to mitigating normal age-dependent cognitive decline, as well as for tauopathies like Alzheimer’s disease and related dementias.

Covalent Bioscience have previously demonstrated the therapeutic potential of catabodies in a recent publication targeting Transthyretin (TTR) that forms misfolded b-sheet aggregates responsible for age-associated amyloidosis. In this paper they have described catabodies from healthy humans without amyloidosis that degraded misfolded TTR (misTTR) without reactivity to the physiological tetrameric TTR (phyTTR) (PMID: 24648510).

Team Members

We’re Hiring!

Please visit the Work With Us page to learn about available positions.

Principal Investigator

Dr. Amit Sharma

Dr. Amit Sharma

Dr. Amit Sharma was awarded a Master’s degree in Biomedical Sciences from Delhi University, India.  He received his PhD in 2009 in Biotechnology from University of Pune for his work demonstrating microRNA regulation of cytokines involved in allergic inflammation in mice model. Dr. Sharma’s postdoctoral research at the Buck Institute, Novato California involved investigating novel molecular regulatory pathways involved in genotoxic stress and cellular senescence in invertebrate and mammalian models.

Dr. Sharma has recently joined SENS Research Foundation as Group Lead in the Senescence Immunology Research Group. His research focus involves studying how aging and senescence affects the immune system and his research group will also investigate strategies to harness the immune system in mitigating deleterious effects of senescent cells with translational focus.

Publications

Previous Publications by Dr. Sharma

Sharma A, Kumar M, Aich J, Hariharan M, Brahmachari S.K, Agrawal A and Ghosh B. Post-Transcriptional Regulation of Interleukin-10 Expression by hsa-miR-106a. Proc Natl Acad Sci U S A. 2009; 106: 5761-6. PMC 2659714

Sharma A, Kumar M, Ahmad T, Mabalirajan U, Aich J, Agrawal A and Ghosh B. Antagonism of mmu- mir-106a attenuates asthma features in allergic murine model. JAP, 2012.

Kumar M, Ahmad T, Sharma A, Mabalirajan U, Kulshreshtha A, Agrawal A, Ghosh B. Let-7 microRNA- mediated regulation of IL-13 and allergic airway inflammation. J Allergy Clin Immunol. 2011. PMID 21616524 

Kumar S, Sharma A and Madan B, Singhal V and Ghosh B. Isoliquiritigenin inhibits IkappaB kinase activity 
and ROS generation to block TNF-alpha induced expression of cell adhesion molecules on human 
endothelial cells. Biochem Pharmacol. 2007; 73:1602-12. 


Tanveer A, Mabalirajan U, Sharma A, Ghosh B, Agrawal A. Simvastatin Improves Epithelial Dysfunction 
and Airway Hyperresponsiveness: From ADMA to Asthma. Am J Respir Cell Mol Biol. 2011 Apr;44 (4):531- 
9. PMID 2055877

Ghosh B, Kumar S, Balwani S, Sharma A. Cell adhesion molecules: therapeutic targets for developing 
novel anti-inflammatory drugs. Advanced Biotech. 2005; 4:13-20. 


Sharma S, Sharma A, Kumar S, Sharma S.K. and Ghosh B. Association of TNF haplotypes with Asthma, 
Serum IgE levels and correlation with serum TNF-α levels. Am J Respir Cell Mol Biol. 2006; 35: 488-95.

Sharma A, Joseph Wu. MicroRNA Expression Profiling of Human Induced Pluripotent and Embryonic Stem Cells. Methods in molecular biology, a part in Springer Science. PMC 3638037

Sharma A, Diecke S, Zhang WY, Lan F, He C, Mordwinkin NM, Chua KF, Wu JC. The role of SIRT6 protein in aging and reprogramming of human induced pluripotent stem cells. J Biol Chem. 2013. PMID 23653361.

Lang S, Bose N, Wilson K, Brackman D, Hilsabeck T, Watson M, Beck J, Sharma A, Chen L, Killlilea D, Ho S, Kahn A, Giacomini K, Stoller M, Chi T, Kapahi P. A conserved role of the insulin-like signaling pathway in uric acid pathologies revealed in Drosophila melanogaster. bioRxiv 387779

Akagi K, Wilson K, Katewa SD, Ortega M, Simmons J, Kapuria S, Sharma A, Jasper H, Kapahi P. Dietary restriction improves intestinal cellular fitness to enhance gut barrier function and lifespan in D. melanogaster. PloS Genet. 2018 Nov 1; 14(11):e1007777. PMC6233930.

Sharma A, Akagi K, Pattavina B, Wilson KA, Nelson C, Watson M, Maksoud E, Ortega M, Brem R, Kapahi P. Musashi expression in intestinal stem cells attenuates radiation-induced decline in intestinal homeostasis and survival in Drosophila. Sci Reports. 2020 Nov 5;10(1):19080.

Full list of published work as found in My Bibliography:

https://www.ncbi.nlm.nih.gov/sites/myncbi/amit.sharma.2/bibliography/55316754/public/?sort=date&direction=ascending

Photos

Resources

Funding

To support our work please consider making a donation to SENS Research Foundation!

Thanks to our existing funders:

Engineering New Mitochondrial Genes to Restore Mitochondrial Function (MitoSENS)

  • Research Info
  • Team Members
  • Publications
  • Photos
  • Funding
  • Research Info
  • Team Members
  • Publications
  • Photos
  • Funding

Mitochondria perform and support several vital functions in a cell, and the alternate genome, mtDNA, plays a critical role in organelle maintenance. There is increasing evidence that mitochondrial function declines with age, and that dysfunctional mitochondria adversely contribute to several metabolic and neuromuscular diseases. Our goal is to address age-acquired and inborn errors of mutation in the mtDNA using a gene therapy approach. We are exploring:

  1. allotopic expression (expressing mtDNA genes from the nucleus), and
  2. whole-organelle replacement

as strategies to revitalize mitochondrial function. Our multidisciplinary approach employs cell culture and mouse models to achieve our objectives.

Allotopic Expression of Proteins Encoded in the Mitochondrial DNA

Mitochondria are the ‘power plants’ in every mammalian cell responsible for the efficient conversion of nutrients to energy. Impaired mitochondrial function and mutations in mtDNA contribute to several age-related illnesses, including Alzheimer’s Disease, Parkinson’s disease, and sarcopenia. Point mutations in any of the 13 protein-coding regions, as well as micro- and macro- deletions in the mtDNA, lead to several monogenic and organelle-specific diseases (MELAS, MEERF, LHON, Leigh’s disease to name a few). However, alterations in the OriH / OriL regions in the mtDNA can lead to global impairment in the transcription and translation of the mitochondrial genome. The mitochondrial proteome, however, consists of ~1400 proteins of which all except for the 13 polypeptides translated on the mitochondrial genome originate from the host’ nucleus. Over the course of evolution, mitochondria have developed sophisticated mechanisms to import these nuclear mitochondrial proteins. These mechanisms employ intricate translocases and signals, which are directed to different regions within the organelle.

The goal of this project is to determine how we might achieve optimal parameters for coding and non-coding regions to efficiently express and target the 13 mtDNA genes to the respiratory chain from the nucleus. Toward this end, we employ molecular biology, biochemistry and computational strategies, and refine and build on our existing knowledge of import conditions for the numerous nuclear mitochondrial proteins already delineated. We use patient-derived cybrids and animal models in assessing the functional utility of our constructs. Ultimately, we aim to express the mtDNA genes individually or in combination to overcome age-related changes to the mtDNA and improve overall organelle fitness. Please see here for recent progress on this project.

Reversing Age-Induced Mitochondrial Damage through Organelle Transplantation

Intercellular mitochondria exchange occurs naturally in the human body between cell types, typically between healthy and damaged cells. Three different transfer mechanisms have been observed:

  1. stem cells release naked mitochondria that are taken up by other cells,
  2. mitochondria are released extracellularly, enclosed in vesicles that are in turn taken up by recipient cells (possibly via endocytosis), or
  3. mitochondria migrate from one cell to another through specialized structures in vivo, such as nanotubes.

The goal of this project is to evaluate the potential of mitochondrial transfer to counteract age-related loss of tissue function. We aim to develop strategies to purify viable mitochondria and deliver them to target regions in the body.

Team Members

We’re Hiring!

Please visit the Work With Us page to learn about available positions.

Principal Investigator

amutha-boominathan

Amutha Boominathan, PhD

Research Staff

BhavnaDixit-1a-o

Bhavna Dixit, MS (Research Associate II)

begelman

David Begelman, BS (Research Associate I)

Carly Truong_headshot

Carly Truong, BS (Research Technician)

Postbaccalaureate Fellows

Summer Scholars

Placeholder-Person-1

Jay-Miguel Fonticella (Class of 2022, Tufts University, BS)

Emily Wallace_headshot

Emily Wallace (Class of 2024, U Mich. BSE)

Lab Alumni

Research Staff

  • Jayanthi Vengalam (2012-2015) – now at Protagonist Therapeutics
  • Shon Vanhoozer (2014-2017)
  • Kathleen Powers (2015-2017) – now at Bristol Myers Squibb
  • Caitlin Lewis (2017-2021) – now at SENS Research Foundation CSO Team

Summer Scholars and Postbaccalaureate Fellows

Publications

Photos

Resources

Funding

To support our work please consider making a donation to SENS Research Foundation!

Thanks to our existing funders:

The Foster Foundation

Enhancing Innate Immune Surveillance of Senescent Cells

  • Research Info
  • Team Members
  • Publications
  • Resources
  • Photos
  • Funding
  • Research Info
  • Team Members
  • Publications
  • Resources
  • Photos
  • Funding

When normal cells lose their ability to replicate, they become senescent cells. Over time, senescent cells accumulate in aging tissues, spewing off a cocktail of inflammatory and growth factors, as well as enzymes that break down surrounding tissue and cause inflammation. This phenomenon is known as the “senescence-associated secretory phenotype” (SASP). Senescent cells – and the downstream impact of the SASP – are now implicated in a remarkable litany of the diseases of aging.

On a more encouraging note, multiple studies have now documented that “senolytic” drugs and gene therapies that destroy senescent cells exert sweeping rejuvenating effects in aging, both in laboratory animals and animal models of multiple diseases of aging. In theory, however, senolytic therapies shouldn’t be necessary. The body’s immune system is on continuous patrol against senescent cells: our natural killer (NK) cells recognize senescent cells as abnormal, bind to them, and release substances that trigger the senescent cells to self-destruct.

An SRF-donor-funded collaboration between Dr. Judith Campisi’s lab at the Buck Institute and the SRF Research Center seeks to discover why senescent cells accumulate with age, and what might we do to enhance immune surveillance and elimination of these cellular saboteurs?

Research Highlights:

The Campisi lab has recently published three papers describing the underlying mechanism of immune evasion by resistant senescent cells (Pereira et al., 2019, Munoz et al., 2019, and Kale et al., 2020). Dr. Campisi has found that a significant proportion of senescent cells manage to evade destruction, even by fresh NK cells. These ‘resistant’ cells escape immunosurveillance and accumulate in aging tissues. Senescent cells moreover shed decoy ligands binding to NK cell receptors; another aim of this work is to screen for more such ligands shed by senescent cells.

The Buck-SRF-RC collaboration is now seeking to drill further into the mechanism of senescent cell accumulation, and test interventions. At the SRF-RC, we are currently perfecting the method of co-culturing NK and senescent cells and controlling the killing process;  next, we will begin testing therapeutic interventions.

The SRF-RC scientists are also working for the first time with NK cells derived directly from aged human donors (rather than long-cultured lines of NK cells, or NK cells artificially “aged” by exposure to oxidative stress or extensive replication in culture, as has been done in the past). Using these cells will allow them to observe any direct effects of aging on NK cell senolytic activity.

Goals:

The primary goal of the laboratory is to find ways to avoid the accumulation with a focus on the immune system:

  • Reversing diminished immune surveillance
  • Use of NK cells to remove senescent cells

Goal 1: Natural killer cells are primary drivers of immune surveillance of senescent cells. This project involves isolation and characterization of age-dependent changes in the phenotypes of Natural Killer cells. This is to investigate if the age of subjects effects the ability of NK cells to eliminate senescent cells in vitro and in vivo.

Goal 2: We have identified several unique antigens expressed on the surface of senescent cells. The goal of this project is the targeted elimination of senescent cells by CAR-NK therapy. We are characterizing the surface an antigen on senescent cells and investigate if targeting this antigen can enhance NK cell-mediated clearance of senescent cells from patient-derived primary endothelial cells and fetal lung fibroblasts. The ultimate goal of the project is to demonstrate that the CAR-NK cells that are capable of eliminating senescent cells in ex vivo and mouse models.

Goal 3: Senescent cells are known to secrete a unique mixture of proinflammatory cytokines, chemokines and matrix modifying proteins called the SASP (Senescence Associated Secretory Phenotype). We have identified several SASP factors that may block immune surveillance by NK cells. Proof of principle experiments are currently being performed to investigate if selective removal of specific SASP factors can enhance immune surveillance of senescent cells. The long-term goal of this project is to develop therapeutic interventions based on removal of these SASP proteins for aging and related diseases.

Team Members

We’re Hiring!

Please visit the Work With Us page to learn about available positions.

Principal Investigator

Dr. Amit Sharma

Dr. Amit Sharma

Dr. Amit Sharma was awarded a Master’s degree in Biomedical Sciences from Delhi University, India.  He received his PhD in 2009 in Biotechnology from University of Pune for his work demonstrating microRNA regulation of cytokines involved in allergic inflammation in mice model. Dr. Sharma’s postdoctoral research at the Buck Institute, Novato California involved investigating novel molecular regulatory pathways involved in genotoxic stress and cellular senescence in invertebrate and mammalian models.

Dr. Sharma has recently joined SENS Research Foundation as Group Lead in the Senescence Immunology Research Group. His research focus involves studying how aging and senescence affects the immune system and his research group will also investigate strategies to harness the immune system in mitigating deleterious effects of senescent cells with translational focus.

Postdoctoral Fellow

Research Associate

Kristie_web

Kristie Kim
Identification and characterization of the surfaceome of senescent cells and development of CAR-NK cells to enhance immune surveillance

Postbaccalaureate Fellow

Gina Zhu (Postbaccalaureate Fellow, 2020-2021)
Identifying Novel Mechanisms to Enhance Natural Killer Cell Mediated Surveillance and Clearance of Senescent Cells

Summer Scholar

Chloe Amber Lindberg (Summer Scholar, 2021)
Investigating the effect of senescence-associated secretory phenotype (SASP) factors on NK cell function

Lab Alumni

Elena Fulton (Postbaccalaureate Fellow, 2019-2020)
Characterization of age dependent changes in peripheral NK cell phenotypes in humans

Mikayla Stabile (Summer Scholar, 2020)
Characterization of age dependent changes in peripheral NK cell phenotypes in humans

Publications

  • Kale A, Sharma A, Stolzing A, Desprez PY, Campisi J. Role of immune cells in the removal of deleterious senescent cells. Immun Ageing 2020 Jun 3;17:16. PubMed: 32518575.

Previous Publications by Dr. Sharma

Sharma A, Kumar M, Aich J, Hariharan M, Brahmachari S.K, Agrawal A and Ghosh B. Post-Transcriptional Regulation of Interleukin-10 Expression by hsa-miR-106a. Proc Natl Acad Sci U S A. 2009; 106: 5761-6. PMC 2659714

Sharma A, Kumar M, Ahmad T, Mabalirajan U, Aich J, Agrawal A and Ghosh B. Antagonism of mmu- mir-106a attenuates asthma features in allergic murine model. JAP, 2012.

Kumar M, Ahmad T, Sharma A, Mabalirajan U, Kulshreshtha A, Agrawal A, Ghosh B. Let-7 microRNA- mediated regulation of IL-13 and allergic airway inflammation. J Allergy Clin Immunol. 2011. PMID 21616524 

Kumar S, Sharma A and Madan B, Singhal V and Ghosh B. Isoliquiritigenin inhibits IkappaB kinase activity 
and ROS generation to block TNF-alpha induced expression of cell adhesion molecules on human 
endothelial cells. Biochem Pharmacol. 2007; 73:1602-12. 


Tanveer A, Mabalirajan U, Sharma A, Ghosh B, Agrawal A. Simvastatin Improves Epithelial Dysfunction 
and Airway Hyperresponsiveness: From ADMA to Asthma. Am J Respir Cell Mol Biol. 2011 Apr;44 (4):531- 
9. PMID 2055877

Ghosh B, Kumar S, Balwani S, Sharma A. Cell adhesion molecules: therapeutic targets for developing 
novel anti-inflammatory drugs. Advanced Biotech. 2005; 4:13-20. 


Sharma S, Sharma A, Kumar S, Sharma S.K. and Ghosh B. Association of TNF haplotypes with Asthma, 
Serum IgE levels and correlation with serum TNF-α levels. Am J Respir Cell Mol Biol. 2006; 35: 488-95.

Sharma A, Joseph Wu. MicroRNA Expression Profiling of Human Induced Pluripotent and Embryonic Stem Cells. Methods in molecular biology, a part in Springer Science. PMC 3638037

Sharma A, Diecke S, Zhang WY, Lan F, He C, Mordwinkin NM, Chua KF, Wu JC. The role of SIRT6 protein in aging and reprogramming of human induced pluripotent stem cells. J Biol Chem. 2013. PMID 23653361.

Lang S, Bose N, Wilson K, Brackman D, Hilsabeck T, Watson M, Beck J, Sharma A, Chen L, Killlilea D, Ho S, Kahn A, Giacomini K, Stoller M, Chi T, Kapahi P. A conserved role of the insulin-like signaling pathway in uric acid pathologies revealed in Drosophila melanogaster. bioRxiv 387779

Akagi K, Wilson K, Katewa SD, Ortega M, Simmons J, Kapuria S, Sharma A, Jasper H, Kapahi P. Dietary restriction improves intestinal cellular fitness to enhance gut barrier function and lifespan in D. melanogaster. PloS Genet. 2018 Nov 1; 14(11):e1007777. PMC6233930.

Sharma A, Akagi K, Pattavina B, Wilson KA, Nelson C, Watson M, Maksoud E, Ortega M, Brem R, Kapahi P. Musashi expression in intestinal stem cells attenuates radiation-induced decline in intestinal homeostasis and survival in Drosophila. Sci Reports. 2020 Nov 5;10(1):19080.

Full list of published work as found in My Bibliography:

https://www.ncbi.nlm.nih.gov/sites/myncbi/amit.sharma.2/bibliography/55316754/public/?sort=date&direction=ascending

Photos

Funding

To support our work please consider making a donation to SENS Research Foundation!

Thanks to our existing funders:

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.

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