Announcing the new Chairman of the SRF Board of Directors

SRF is pleased to announce that Bill Liao has been appointed Chairman of the Board of Directors.

He’s been serving as a Director and Board Secretary since the beginning of SRF. Bill Liao is a Chinese-Australian-Irish entrepreneur, investor, former diplomat, business mentor, author, passionate leader and speaker, with a distinguished record in business development and community activism. He is co-founder of the CoderDojo movement which teaches children worldwide how to code, and of Weforest, which has a stated goal of planting a hundred million trees around the equator. He has been a member of official delegations to the COP climate change summits. His career in tech and business encompasses two unicorn companies and launching the world’s first bio-tech accelerator. He has participated as an investor and volunteer for The Hunger Project in Uganda, New York, and Mexico. He is a general partner of SOSV, a venture capital fund of over $1B, and founder of the SOSV Momentum Pre-accelerator program. Bill’s current focus is Quantum Software.

Barbara Logan who is stepping down as Chair, has been serving as a Director since the founding days of the organization and we are profoundly grateful for her leadership, guidance and support during all these years, and recently through some of the most difficult times the organization had to face. She remains a Board member.

The members of our Board are dedicated and esteemed persons who bring extensive, diverse experience and commitment to guiding SRF.

We are excited to keep harnessing their knowledge and energy into furthering our mission.

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.

Announcement from the SRF Board of Directors

March 25, 2022

Over the past two years, SRF’s volunteer Board members have devoted unprecedented selflessness – including countless hours and great emotional energy – to their duties as the foundation’s unpaid fiduciaries.

We want to extend our deepest gratitude to our colleagues who, as of March 23, have stepped down from the Board to focus more on their professional endeavors and personal lives.

Michael Boocher
Jonathan Cain
Mike Kope
Frank Schuler

As always, the remaining Directors, together with our remarkable SRF staff, will stay sharply focused on our original mission of curing the disease of aging.

The SENS Research Foundation Board of Directors

 

Announcement from the SRF Board of Directors

In August 2021, the SENS Research Foundation Board of Trustees separated from Dr. Aubrey de Grey, our Co-Founder and then-Chief Science Officer. This was a difficult decision, but, as we said at the time, a necessary one.

In doing so, we wholeheartedly acknowledged that we are an organization that is, and always will be, shaped by Dr. de Grey’s vision for transformation within the longevity field. In that spirit, in December 2021, we began a cautious, but important process of re-unifying with Dr. de Grey – a process aimed at helping both Dr. de Grey and the Board move forward from a difficult and contentious period and refocus our collective efforts on bolstering research that can permanently cure the effects of aging. Dr. de Grey would rejoin the Foundation as a consultant with a pathway toward a full and proper re-integration. Such an arrangement was to be made cautiously, with an eye toward our shared mission, and free from public spectacle.

We regret to report that, effective immediately, Dr. de Grey will no longer be consulting with SRF.

It’s important to note that, as with our previous separation, this is not related to the findings of last year’s independent investigation. While those investigations did substantiate instances of poor judgment and boundary-crossing behaviors, Dr. de Grey is not a sexual predator. Rather, the termination of Dr. de Grey’s consultancy with the Foundation is entirely due to his unwillingness to comply with even the most basic conditions of the agreements he signed with advice from his counsel. In the spirit of transparency, you can access the signed contract here: LINK

The SRF staff is talented, positive, and dedicated to our cause. We want to ensure they can advance their work free from distraction. As a Board, this will become both our sole focus and our promise. Every one of our Directors has worked exhaustively to preserve this Foundation during an unprecedented, challenging time in our history. A number of our members need to move on to other endeavors, but we will be looking to expand the Board and further the cause in the near future. We are grateful for every member’s service and commitment to the longevity field, as well as their strength in making these difficult but necessary decisions.

It is SRF’s intention that we and Dr. de Grey can continue to work in a way that is aligned toward a common purpose: to cure the disease of aging. Until such time, we will do all we can to assure you we are navigating this situation in a manner that honors our mission and fiduciary duties while respecting the legacy of our founding.

Sincerely,

The SENS Research Foundation Board of Directors

Michael Rae and Dr. Robert Rodgers discuss Parkinson’s and aging

Parkinson’s disease, like all the so-called diseases of aging, is what happens when the particular metabolic demands on specific cell and tissue types inflict enough damage on themselves to render them unable to do their jobs. As more and more of those cells and tissues become dysfunctional over time, the functional reserve of those tissues is slowly drained, until core function can no longer be sustained and the symptoms of that widespread cellular and molecular injury erupt.

In this interview with the Parkinson’s Recovery radio program, SENS Research Foundation’s science writer Michael Rae discusses “The coming rejuvenation biotechnology revolution for Parkinson’s disease.” In it, they discussed how the cellular and molecular damage of aging most closely involved in Parkinson’s can be removed, replaced, or repaired using rejuvenation biotechnologies, and research underway to make it happen. Here is some of what they talked about.

New Cells for Old …

The most prominent kind of aging damage driving Parkinson’s is the loss of specialized neurons producing the molecular messenger dopamine in a defined area of the brain. Signaling from these neurons suppresses the unregulated firing of neurons controlling motion in the brain, so as these neurons are lost to aging and additional insults, the ability to suppress this unwanted firing declines. Eventually, this becomes manifest as the “motor symptoms” of Parkinson’s: the tremors of the hands, shaking of the head, and problems with walking balance.

The rejuvenation biotechnology solution to this problem is repleniSENS: replacing the lost dopamine-producing neurons with fresh young ones. Early human clinical trials using cells derived from aborted fetuses had mixed results, but a small percentage of the patients who received the cells experienced such spectacular results scientists spent the next several decades working out the cell types, transplant sites, and other details to optimize the procedure so that all people suffering PD  (and eventually, all of us) could benefit.

In addition to what we learned through the ensuing decades of painstaking progress, we now have Shinya Yamanaka’s Nobel-prizewinning biotechnological breakthrough: the ability to take common differentiated cells (such as deep-layer skin cells) and reprogram them into  induced pluripotent stem cells (iPSC), which have the full developmental potential of embryonic stem cells and can be nudged to become any cell type we like — including dopamine-producing neurons for cell replacement.  Today, BlueRock Therapeutics, a stem cell company now owned by Bayer (yes, the aspirin people) is running a clinical trial grafting replacement neurons into the brains of patients with PD. Unlike others, BlueRock is not starting the process off with a patient’s own cells, but is using healthy donor cells from the general public, from which it then uses proprietary bioprocessing to create stable master cell banks of what they call “universal iPSCs” that they have found to be compatible with any patient. It is these cells that are then turned into dopaminergic neurons for transplant into the brain of PD patients — or, in the future, heart muscle cells for people with heart failure, and other medical use-cases.

Other groups are taking the patient-identical route. These include Dr. Jun Takahashi of Kyoto University in Japan, whose small ongoing trial recruited just 7 subjects and administered cells to its first patient in November of 2018, and Aspen Biotechnologies, which is led by Dr. Jeanne Loring at the Scripps Institute, a good friend of SENS Research Foundation. Additionally, it was only just revealed last year that a dramatic self-funded experiment by a wealthy PD sufferer resulted in millions of his own reprogrammed cells being transplanted into his brain as early as September 2017. And we’re even still learning things about grafting fetal neurons, because of a revamped European trial with curtailed ambitions known as Transeuro.

… And Out with the Old!

Meanwhile, we’ve learned about the evidence supporting a causal role for senescent cells in PD — and the potential of apoptoSENS (destruction of dysfunctional cells) to help keep these “zombie” cells from destroying some of those dopamine-producing neurons in the first place. People with PD have more senescent cells in their brains than do aging people not diagnosed with a specific neurological disease — specifically, senescent astrocytes, which help maintain the integrity of the crucial barrier that protects the brain from toxins in the circulation, and that also act as a kind of support cell for the neurons, providing them with nutrients and maintaining the balance of ionic flows. Scientists led by Julie Anderson and Judith Campisi at the Buck institute showed in animal models and cell culture that when astrocytes turn senescent, betray the very neurons they exist to protect and support, killing them.

But purging senescent astrocytes from the brains of mice with a model of PD prevented the loss of dopamine-producing neurons and enabling the generation of new neurons to begin again. This meant that after senolytic treatment, the PD mice were still able to move like non-PD mice. With ongoing trials of senolytic drugs and a host of startups in the space, the potential to bring this experiment to life in aging humans is breathtaking.

The Roto-Rooter Route to Rejuvenation

They also talked about the many lysoSENS immunotherapies in clinical trials or in the pipeline to remove aggregated alpha-synuclein from aging neurons and prevent the “nonmotor symptoms” of PD, and the related role of “minor” mutations in a lysosomal enzyme that create a vicious circle with alpha-synuclein — and Aspen Biotechnology’s plans to eliminate the problem.

And much more! Hear the full audio here.

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.

Executive Summary, Final Investigative Report

Dear SENS Research Foundation Community:

Today, we are releasing the Executive Summary concerning the second of two investigations into the conduct of SRF’s Founder and former Chief Science Officer, Dr. Aubrey de Grey. As this report notes, during the course of SRF’s first investigation into Dr. de Grey’s conduct, “witnesses reported Dr. de Grey may have engaged in inappropriate conduct toward others.” In the interest of accountability, we expanded the investigator’s scope to look into these allegations as well. It’s important to note that this investigation was an extension of, rather than a reassessment of, the initial investigation.

As you will see in the enclosed report, the investigator affirms some additional, limited boundary-crossing and unprofessional behaviors had occurred over a 12-year period.  We hope this report helps to bring closure to the individuals who came forward to raise concerns, and also to our larger longevity community.

This investigation and its findings do not have any bearing on the SRF Board of Directors’ unanimous decision to separate from Dr. de Grey in response to his unacceptable interference during the initial phase of the investigation. The SRF Board has not officially deliberated (and will not officially deliberate) on whether either report’s findings might have led to Dr. de Grey’s termination or other disciplinary matters.

This report concludes SRF’s work with its independent investigator, Van Dermyden Makus. We are deeply grateful to the investigators for their guidance, their diligent work and their professionalism during this challenging chapter in the life of the Foundation.

The release of this report also symbolizes a page turning of sorts for SRF – the closure of a difficult and disruptive period in our history. With an eye toward the future and the great work ahead of us, bolstered by strong interim leadership, scientists and staff, we now move forward with a renewed commitment and sharpened focus on our goal of advancing innovation within the longevity field.

Our respect for Dr. de Grey and his work remains deep and unwavering. His accomplishments are singular; he brought this Foundation — this profound scientific moment, truly — into being. While our separation was necessary, we intend to move forward with SRF in a way that honors his legacy.

We remain deeply grateful to the SRF team and our supporters for not losing faith during an unsettling time. In the months and years ahead, we will do all we can to honor your trust.

Onward,

The SENS Research Foundation Board of Directors

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

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