Aging of the Immune System: Focus on Natural Killer Cells Phenotype and Functions

We are proud to announce the recent publication by the ApoptoSENS team led by Dr. Amit Sharma in the journal Cells describing the role and controversies involving the aging of Natural Killer (NK) cells and age-related NK cell dysfunction.

NK cell dysfunction is implicated in the increasing burden of infection, malignancy, inflammatory disorders, and senescent cells with age.

This review focuses on recent advances and open questions in understanding the interplay between systemic inflammation, senescence burden, and NK cell dysfunction in the context of aging and potential therapies for age-related diseases.

Authors: Ashley Brauning, Michael Rae, Gina Zhu, Elena Fulton, Dr. Tesfahun Dessale Admasu, Prof. Alexandra Stolzing, Dr. Amit Sharma contributed to this publication.

DOI: 10.3390/cells11061017

Categories SRF

New Peer-Reviewed Paper from SENS Research Foundation Reports a Better Method to Study How Immune Cells Seek and Destroy Senescent Cells

Senolytics — drugs that selectively destroy senescent cells (senolytics) — have been shown to powerfully rejuvenate mice and to reverse multiple diseases of aging in animals, from atherosclerosis, to kidney disease, to osteoporosis, to Parkinson’s disease — and beyond. But because these drugs target pathways that are necessary for normal cell function, they can come with side-effects — the most notable being the crash in platelets (and resulting risk of fatal bleeds or strokes) that can accompany the experimental senolytic navitoclax.

But our bodies are actually equipped with an inborn army of immune cells that selectively identify and destroy senescent cells. To date, the most important of these “immunosenolytic” cells soldiers have seemed to be Natural Killer cells (NK cells) — though we will have an announcement to make on this front in the coming months. But if the body already has this defensive force, how do senescent cells still manage to accumulate in our tissues with age and wreak havoc on our health?

As part of SENS Research Foundation’s work to eradicate dysfunctional cells driving aging (ApoptoSENS), Dr. Amit Sharma and his team at SRF are developing ways to either rejuvenate our own NK cells’ ability to detect and destroy senescent cells in aging tissues, or to augment that capacity with NK cells engineered to be more lethal senescent cell hunters. To reach those goals, they realized they needed a more efficient way to enrich NK cells from mixed white blood cells isolated from human blood. In new peer-reviewed scientific paper, they show how they did it.

Their main innovation might seem to be an obvious one: to actually isolate NK cells and activate them to better mimic the situation in vivo. Previous studies have mostly used mixed populations of blood cells, sometimes removing T-cells or other specific cell types but never ensuring that they had isolated NK cells exclusively. Dr. Sharma used an existing kit to make sure that what they were seeing came from the NK cells and not from other cell types.

They also saw that the way that previous researchers had studied NK cells’ ability to destroy senescent cells was quite different from the conditions NK cells actually confront as they patrol for NK cells in the body, potentially leading scientists to chase after interventions that work well in a Petri dish but have no effect or are unsafe when carried out in living, breathing humans. This is probably because most scientists conducting these studies don’t have a specialized background in immunology: instead, they design their experiments based on a general background in the biology of aging or cancer biology, or as specialists in senescence per se, but

The biggest problem the SRF group corrected is that previous studies have cultured low numbers of senescent cells together with very high numbers of NK cells, creating a situation where NK cells are effectively shooting zombie fish in a barrel. Dr. Sharma’s team tested more realistic conditions in which one NK cell encounters one senescent cell, or no more than three, instead of ratios as high as one senescent cell target to 20 or even 80 NK cells.

Conversely, having given NK cells so many senescent cell targets that they can hardly fail to kill some, most previous studies have only set NK cells loose for a few hours, when NK cells have a half-life in the body of ten hours. So the ApoptoSENS team led by Dr. Sharma gave NK cells more time to engage their enemies, which better reflects how long they actually hang out in tissues, with experiments running from 16 hours to four days. This also gives the NK cells the ability to reveal their full range of powers, since some of their cell-killing weapons only engage over extended time periods.

Finally, previous studies on NK cells’ immune surveillance of senescent cells have cultured them in very high levels of interleukin-2 (IL-2), an immune-signaling molecule that triggers NK cells to create more of themselves and makes them more aggressive. At SRF, Dr. Sharma used levels that reflect levels in the body.

The first set of discoveries revealed by this new system: even when the ratio between NK and their potential targets is quite low, introducing more NK cells into the mix tends to kill more senescent cells, but at the expense of killing more and more healthy bystander cells.

All around, the new paper sets up the SRF ApoptoSENS team — and other scientists who can now read the findings for themselves — on a better path to identify ways to rejuvenate or reinforce senescent cell immune surveillance, reinvigorating NK cells to make them battle-ready once again.

Reference

Kim K, Admasu TD, Stolzing A, Sharma A. Enhanced co-culture and enrichment of human natural killer cells for the selective clearance of senescent cells. Aging (Albany NY). 2022 Mar 4;14(5):2131-2147. doi: 10.18632/aging.203931. Epub 2022 Mar 4. PMID: 35245208; PMCID: PMC8954966.

We are thrilled to announce the expansion of our Research Center

We are thrilled to announce the expansion of our Research Center to over 11,000 sq. feet with the addition of new lab and office space. This is more than doubling our current facility in Mountain View California that is home to SRF’s global operations. 

Thank you to all the donors who made this expansion possible. We are grateful beyond words for your ongoing support, as it has enabled us to rapidly expand not just our lab space, but our internal research programs, as well as the equipment and other resources needed to accelerate the defeat of age-related disease.

We will host a Grand Re-Opening early this summer to which everyone will be invited – watch your inbox and stay tuned for details.

SRF Celebrates Women’s History Month

Throughout history, women interested in science and engineering have broken barriers to make important discoveries, conduct game-changing research, and pursue careers in science, technology, engineering, and math (STEM).

Rosalind Franklin’s x-ray crystallography work was critical to the discovery of DNA’s double-helix structure. Although she received recognition for her discoveries on coal and viruses, her contributions to the structure of DNA were largely unrecognized in her lifetime. Therefore, she is often referred to as the “dark lady of DNA” and the “Sylvia Plath of molecular biology.” Franklin led pioneering work at Birkbeck College on the molecular structures of viruses. She passed away the day before her structure was to be unveiled. Her continued research eventually won the Nobel Prize in Chemistry in 1982.

Margaret Dayhoff founded the field of bioinformatics. Dayhoff dedicated her career to applying the evolving computational technologies to support advances in biology and medicine. She is best known for the creation of protein and nucleic acid databases and tools to disrupt the databases. She also developed one of the first one-letter codes (PAM) used for amino acids, which reflected an attempt to reduce the size of the data files used to describe amino acid sequences. Dayhoff was the first woman to hold office in the Biophysical Society and the first person to serve both as secretary and eventually president.

Esther Lederberg discovered the lambda phage, an important tool for studying gene regulation and recombination. Lederberg also invented the replica plating technique, which is used to isolate and analyse bacterial mutants and track antibiotic resistance. Prior to Esther’s invention scientists had been largely unsuccessful with their techniques, including the use of blotting paper, metal brushes with small prongs and even toothpicks in their experimentation. Lederberg’s work with geneticists at Stanford University greatly assisted their winning of the Nobel Prize in 1958 for discovering the role of genes in regulating biochemical events in cells.

Marie Maynard Daly performed foundational work in histone chemistry, protein synthesis, and the health impacts of cholesterol and hypertension. For seven years, she worked on the composition and metabolism of components of the cell nucleus at the Rockefeller Institute in New York. Daly was the first African American woman to obtain a PhD in chemistry in the United States, at Columbia University. Overcoming the dual hurdles of racial and gender bias, Daly was committed to developing programs to increase the enrollment of minority students in medical school and graduate science programs.

Dr. Kizzmekia Corbett is a viral immunologist known for being the scientific lead of the VRC’s COVID-19 Team, with research aimed at COVID-19 vaccines. Anthony Fauci wrote in a Time’s profile that Corbett has “been central to the development of the Moderna mRNA vaccine and the Eli Lilly therapeutic monoclonal antibody that were first to enter clinical trials in the U.S.” and that “her work will have a substantial impact on ending the worst respiratory-disease pandemic in more than 100 years.” In December 2021, Corbett was assigned to Boston’s COVID-19 advisory committee by mayor Wu.

Encouraging girls to see themselves as future scientists through the unveiling of the role women have played in STEM is important, ongoing work for science educators. SRF encourages the development and support of women in longevity research, both as scientists and as administrators and support personnel. Our Education program teaches the next generation of young women to follow their dreams and make new discoveries to drive our field forward.

We are proud to present the many women of SENS Research Foundation, including our researchers, executive, and administrative teams. SRF is currently 100% female-led internally, with an all-women Senior Staff Team and Chairperson on the Board of Directors. While it does take the entire community of SRF staff and supporters to move our mission forward, this month we are thrilled to highlight the women who continue to drive our progress in longevity research.

Please visit the Team section of our website to learn more about the amazing women of SRF.

Categories SRF

SENS Research Foundation & Underdog Pharmaceuticals jointly awarded $252,000 NIA research grant

The National Institute on Aging (NIA) division of the National Institutes of Health (NIH) has awarded a grant to advance research on Engineered Cyclodextrins targeting toxic oxidized cholesterol to eradicate atherosclerosis — the cause of most heart attacks and strokes.

Former SRF V.P. of Research and current Underdog Co-founder Matthew O’Connor, Ph.D. and current SRF V.P. of Research Alexandra Stolzing, Ph.D., are the Principal Investigators.

Underdog Pharmaceuticals’ research has combined computational and synthetic chemistry programs to custom-engineer cyclodextrins to capture, and remove from cells, oxidized cholesterol derivatives such as 7-ketocholesterol.

Their technology removes the arterial plaque by clearing the non-degradable cholesterol that accumulates within cells in the arterial walls. The grant also supports exploring the use of Underdog’s technology to target oxidized cholesterol in the Alzheimer’s disease brain.

Their long-term goal is to deliver a simple and affordable preventive therapy for the world.

The novel therapeutic approach was born from one of SRF’s flagship research programs designed to understand and repair the underlying causes of cardiovascular disease. SENS Research Foundation and Underdog Pharmaceuticals are very proud to receive this important peer-reviewed NIH grant.

We are excited about how this collaboration will contribute to the advancement of our mission to develop, promote, and ensure widespread access to therapies that cure and prevent the diseases and disabilities of aging.

SRF’s researchers presenting our work at Indian biosciences conferences

Our VP of Research Dr. Alex Stolzing and Senescence Immunology Research Group Lead Dr. Amit Sharma will be presenting at conferences in India

Dr. Stolzing will be presenting a talk on “Aging Interventions – an update” at the 35th Annual Conference of Aging Interventions, organized by the Society of Neurochemistry, India (SNCI), running from December 2nd-4th, 2021.

Dr. Sharma will also presenting a talk titled “ ‘Engineering Natural Killer cells: Improving immune surveillance of senescent cells in aging and age-related diseases’” at the Conference. 

The conference will have attendees at University of Hyderabad, Gachibowli, as well as remote attendees via video conferencing.

Dr. Stolzing will also be a panelist at the Darwin International Conference, also hosted in India, and will be discussing: “Aging: a curable disease or an inevitable process?”. The Darwin International Conference is a virtual conference running from December 2-5, 2021.

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

At the end of the Sacrifice phase, you will receive a notice via email confirming:

  • your donation,
  • the USD value that it was liquidated at, and
  • the ETH address to be sent to Richard Heart.

If this information is correct, please do not respond to the notice. If it is incorrect, please contact [email protected] to correct the information.

It is important to note that Richard Heart has requested that the USD value of your donation be listed at the value it was liquidated, not received. We guarantee liquidation of all non-fiat donations within 12 hours of receipt, however we will strive for within an hour of receipt. Please note that prices of cryptocurrencies vary widely and we will do our best (for you and for us) to liquidate your donation as quickly as possible to minimize any value discrepancy.

Tax Considerations

United States Citizens:
SRF can provide a donation receipt to any donor. All donors will receive a donation receipt for tax purposes, however you may want to include your full name so that we can include that on your donation receipt. Please note that only US tax payers can use this donation receipt for their taxes. The donation value for tax purposes is the USD value of donation at the time of donation.


United Kingdom Citizens:
SENS Foundation Europe is a registered charity in the UK and is accepting donations for the Airdrop initiative. They accept bank transfers, wires, checks, and cryptocurrencies. Email our Airdrop address if you need further information.


European Citizens:
SENS Foundation Europe partners with Transnational Giving Europe (TGE) to provide tax benefits to European citizens in their country of residence. Please go to this link to see if there is an affiliated charity in your country. You will need to contact the charity in your country to see what donations they accept and to direct your donation to SENS Foundation Europe. Please email if you have any issues.


Canadian Citizens:
Tax-deductible receipts for donations made to the Canadian Charity, Aging Research Network (http://www.agenet.org) (ARN) will be accepted for the Airdrop Initiative. Please contact us for more information on donating to ARN. This will provide Canadian citizens with a tax benefit, but can only accept fiat currency at this time. Please email for further information and instructions.

SRF Publication on Mitochondrial Genome in Aging and Disease and the Future of Mitochondrial Therapeutics

Dr. Amutha Boominathan and the MitoSENS team continue to make progress in developing rejuvenation biotechnologies to prevent, reverse, or remove mutant mitochondria from aging cells. The center of their work continues to be allotopic expression: Dr. Aubrey de Grey’s proposal to place “backup copies” of the mitochondrial DNA into the nucleus, which would supply the proteins that mutation-bearing mitochondria can no longer produce for themselves, and thus keep them (and our cells) functioning normally over time.

The MitoSENS team’s  2016 breakthrough  with allotopic expression of the mitochondrial genes ATP8 and ATP6 marked an important milestone. Since then, they’ve continued to work to advance the field, including showing how the distinct way that mitochondria encode genetic instructions into their DNA can be better “translated” for use in the nuclear genome, resulting in robust but transient protein production for all of the 13 genes. The team is now working on creating stable expression for these proteins and in achieving functional relevance. They also developed a new, easier, and cheaper way to isolate mitochondria from cells for scientific investigation, taking some of the cost and friction out of their own work and that of other mitochondrial engineers.

Schematic for Allotopic Expression. The various steps involved in the successful implementation of the allotopic expression strategy are depicted, beginning with design of the optimal DNA expression construct and ending with incorporation of the exogenous protein into the correct RC complex. HR: homologous region, UTR: untranslated region, MTS: mitochondrial targeting sequence, IMS: intermembrane space, IM: inner membrane, RC: respiratory chain.

Saravanan S, Lewis CJ, Dixit B, O’Connor MS, Stolzing A, Boominathan A. The Mitochondrial Genome in Aging and Disease and the Future of Mitochondrial Therapeutics. Biomedicines. 2022; 10(2):490. https://doi.org/10.3390/biomedicines10020490

In a new peer-reviewed scientific paper, the MitoSENS team gives an overview of where the field is at and the obstacles that are holding us back. They first highlight some of the drugs, supplements and stem cell treatments that have been tried and failed (or only had modest effects) to treat inherited mitochondrial diseases. But then they get to the heart of the matter: the challenges that now need to be overcome in order to move allotopic expression towards the clinic. These include mastering the targeting of allotopically-expressed proteins to the right place in the mitochondria; modifying either the protein products themselves or the way we deliver them to prevent these proteins being incorrectly assembled in places other than their intended location; and controlling the level of protein production and its regulation by the cell (since too little protein production wouldn’t have a therapeutic effect, and too much might be harmful).

Another hurdle that is slowing down progress toward working MitoSENS therapies is the lack of good animal models for testing allotopic expression. Testing the potential of allotopic expression will also require safe and stable gene therapy with broad tissue coverage that can deliver much larger payloads than have been required for most human gene therapies to date.

Despite all of these challenges, there have nonetheless been proofs-of-concept reports for allotopic expression in laboratory animals. However, only one such attempt has advanced to any therapeutic benefit, namely, allotopic expression of the ND4 gene to treat LHON (Leber’s Hereditary Optic Neuropathy). A critical study along the way to the emergence of this therapy was one funded by the Methuselah Foundation (from which SENS Research Foundation spun out) almost fifteen years ago. The French scientists responsible for this study followed it up with a more thorough and convincing follow-on study, which allowed the scientists and their industry partner GenSight to ultimately move it into a successful initial human clinical trial to rescue function although only at the organ level (the eye). Their recent REFLECT Phase III clinical trial confirmed that their mitochondrial gene therapy product for patients with LHON had long-term sustained effects in improving visual acuity in patients.

The basic- and translational-science barriers identified in this paper are extensive and long-standing challenges. Innovations in gene editing and gene therapy technologies and advances by the MitoSENS group and other researchers around the world give promise to find meaningful therapies for such diseases going forward.

Categories SRF

MitoMouse Project

Work supported by the 2015 MitoSENS crowdfunding initiative demonstrated that our strategy to neutralise mitochondrial mutations works in cell culture. Now, our new MitoMouse project aims to prove that the same technique can work in live mice. Can you help us raise the $50,000 we need?

Categories SRF

Rejuvenation Now!

The Forever Healthy Foundation has launched a new “Rejuvenation Now” initiative, designed to identify rejuvenation therapies that are available right now and evaluate their risks and benefits. Analyses of NAD+ Restoration Therapy and Fisetin Senolytic Therapy are now available to read.

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