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Proceedings from Longevity Science Conferences 2021

Ending Age-Related Diseases 2021

This post is in-progress!  The conference just ended on Aug. 22;  as I clean up my notes, I'll post them here.  Please come back for future updates...

Link to conference


 (Notes and screenshots taken - and sometimes annotated - by me.  I will later contact the presenters to offer them the option to review them for accuracy...)

Science at SENS Research Foundation 2021

Talk by Alexandra Stolzing, Professor for Biogerontological Engineering, VP of Research at SENS Research Foundation ("Strategies for Engineered Negligible Senescence".)

This overview talk immediately emphasizes that the aging process involves multiple broad fundamental categories of physiological change.  Those are related to what are often referred as "the Hallmarks of Aging", as I detail in my intro post on Longevity Science.  In this talk, 7 of those categories are identified, and given convenient icons (rightmost column) that make it easier to refer to them:

The SENS foundation has both intramural and extramural projects happening, and tries to have at least one project in each of the above broad categories.  (But currently no project in the "OncoSENS" category; submissions are encouraged!)

External projects at SENS include the following:

More info on SENS's external projects; in particular, the above ones:

  1. Target Prioritization of Tissue Crosslinking
  2. Functional Neuron Replacement to Rejuvenate the Neocortex
  3. Therapy to Destroy Cells with Reactivated “Jumping Genes” 
  4. Lipofuscin Degradation by Bacterial Hydrolases

Moving on to intramural projects... if the mitochondrion slackens off, can the nucleus take over its genes?  In-vivo work with a mouse model:

The immune system's decline with age has been tragically underscored during the Covid pandemic...  One strategy being explored is trying to eliminate senescent cells in hope of improving immune function.  

[Side note from me: the elimination of senescent cell, in a different context, has been a goal, though without positive outcome so far, of Google's venture into longevity science, Calico Life SciencesHal Barron, the Chief Scientific Officer and President of R&D at the company where I work, pharma giant GSK, was President of R&D at Calico for 3 years, till 2017]

But how to kill off those pesky senescent cells?  How about recruiting "Natural Killers", aka NK cells, and stimulating their natural proclivity to dispatch senescent cells?  Enhancing Innate Immune Surveillance of Senescent Cells.

Troublesome senescent cells, sadly, tend to "corrupt" other cells and instigate them to enter a senescent state, too.  These "second-generation" senescent cells are different - and another project is to figure out how to get rid of those as well:

The SENS Research Foundation likes to incubate projects, typically foundational and remote from direct practical application; the spinoff companies focus on the latter.  Some of them:

 SENS also has educational programs, in collaboration with various institutes:

Grants proposals are accepted by SENS at any time of the year.  Typical grants are US $50 - 350k , for 1-3 years.

SENS is especially interested in combining potential targets (possibly developed by separate companies) and exploring if they have synergy together.

 

(More talks to be added!  Please come back for future updates...)

 ____________________________________________

One talk from last year, but still relevant:

Ending Age-Related Diseases 2020

Acceleration of human rejuvenation trials: The path from research to application

4 key points:

1. We need to monitor people in trials AND out in the wild more frequently and on a wider amount of biomarkers 2. We need to give access to interventions to people and collect data on more interventions and combos 3. We need to start collaborating and finding ways to allow all data to be leveraged to slow aging 4. We need to learn from any failures and iterate more quickly The 6 presenters:

* Aubrey de Grey, PhD, Chief Science Officer and Co-founder, SENS Research Foundation

* Kevin Perrott, PhD, Adjunct Processor at U. of Alberta / CEO at OpenCures [Note: I used to work there, as CTO and science liaison, prior to my current position at GlaxoSmithKline pharmaceuticals]

* Gregory Fahy, PhD, Chief Scientific Officer, Researcher, Intervene Immune

* Sajad Zalzala, MD , Co-Founder, Chief Medical Officer, AgelessRx

* Steve Horvath, PhD, Professor, University of California, Los Angeles

* Michael Geer, Co-Founder, Humanity.

Detailed bullet points from the talk (taken by me and reviewed by all panelists for accuracy): ___________________________________________________________________________ 1. We need to monitor people in trials AND out in the wild more frequently and on a wider amount of biomarkers
• [Kevin] We don't have enough data from healthy humans to describe normal human biology. Why haven't mass spectrometers, generally regarded as a "research" instrument, not been used to help people monitor their health? With a mass spectrometer, we measure a large number of biomarkers. He founded OpenCures to help ordinary people have access to research tools normally reserved for biotech and academia. • [Michael] His own company, Humanity, is following a similar direct-to-consumer path • We need to measure more biological clocks, including from plasma metabolites
• We need to expand methylation measurements • We should do more un-targeted assays - above and beyond the "standard clinical biomarkers"
• [Steve] It's important to have a variety of biomarkers, across various "omics" data. For example, methylation can be robustly measured, but it is not suitable for all interventions - and has multiple varieties, such as blood methylation , or skin, or fat, etc.
• [Steve] Some "omics" data can be very noisy. Their costs ought to be covered by NIH or other organizations funding basic research. • [Aubrey, Steve, Greg] To do good statistics on intervention treatments, it's critical to do a baseline measurement (or better yet 2+) prior to the treatment • [Greg] Baseline measurements - including the familiar "boring" biomarkers - also have helped some people discover health problems they didn't know about, such as poor renal function, early prostate cancer and pre-diabetes • [Kevin] OpenCures does assays for 85 proteins, including the "boring" standard ones normally prescribed by doctors (such as cholesterol.) • [Kevin] "You don't look at the blueprint of your car, to know how well it works! You take it to the smog check, and they measure it". In particular, not enough focus has been placed on the aging of the peroxisomes and cellular membranes. We haven't been able to measure metabolites easily in the past, but that has changed. • [Michael] We need to add more attention to direct-to-consumer methods to allow users to monitor their rate of aging. This includes digital biomarkers from wearable devices.
• We need more "omics" data - and ways to pool it
• [Kevin] The whole purpose of OpenCures is the creation of a collaborative database of multi-omics data. Anybody who has the ability to generate data that is human-relevant for aging : we should "throw it all into the pot" as much as legally possible. The data can be obscured to protect the subjects' privacy.
2. We need to give access to interventions to people and collect data on more interventions and combos
• [Steve] Cocktails of interventions may succeed where individual treatments don't. He works on biomarkers of aging. What the field really needs is one success story! We need to diversify the field - not just do the interventions that everyone has heard about (such as rapamycin.) Also, we need to experiment with interventions that have initially failed, but perhaps could succeed by combining them: "cocktails" could make all the difference. His perception of clinical trials is that people give up too early: by contrast, in basic research, if one fails, one just tries something else.
• [Greg] Aging requires a multi-prong approach. We did a trial recently that involved a cocktail, and the results may not have happened if we had just used one of those agents by itself. That are many pathways involved in aging, and you must target more than one, if you want a more comprehensive solution. We use growth hormone, DHEA and metformin. Our aim was to restore immune function. We need to regenerate the thymus; our research showed some promising signs in that direction. Steve's epigenetic clock, and other clocks - such as computing age from blood plasma metabolites - are all valuable. With InterveneImmune, he's collaborating with Steve. • [Sajad] Using telemedicine and other approaches so that people won't have to jump through too many hoops to try interventions, such as getting prescriptions for rapamycin. Now making the process easier, and also launching a clinical trial for rapamycin at various doses, and compared to placebo.
• [Michael] RWE (Real world evidence) and actually giving people the superpower of monitoring themselves and the effects of interventions will be a major new way of finding ways to slow aging.
• [Greg] Involved in the Health Span Initiative: an open observational clinical trial in the aging space. Help researchers run clinical trials.
3. We need to start collaborating and finding ways to allow all data to be leveraged to slow aging • Expand GenBank to pinpoint new biomarkers
• [Kevin] We need a multi-dimensional version of GenBank that can describe human health. Can we identify more biomarkers, not just the "standard" ones? How about all the rest - the undiscovered biomarkers, the "dark matter" of the field? We need to develop high-volume un-targeted assays to create a data resource, which we could then open to the world. Data data-sharing standards are especially important to that end. We need a way to submit data and have it validated. • Deal with issues sharing data : strategy & methods for new repositories • [Steve] NIH ought to lean on recipients of grants to urge them to make their data public. Open-access to data is NOT a new idea... and is required by many journals... but more could be done; sometime, it takes months to get the data, especially from government-funded agencies. NIH ought to deny grants to any groups that aren't forthcoming about sharing their data; there are some professors who don't want to share their data.
• [Kevin] Working with FASEB (the Federation of American Societies for Biology), working on developing common data standards for data sharing • [Michael] The use of federated learning and differential privacy can allow for privacy preservation of all data and still leverage it to save lives.
4. We need to learn from any failures and iterate more quickly • Investors need a long-term outlook : initial failure are to be expected. Every clinical trial is just an experiment. • For example, a strength of Silicon Valley is to embrace failures • Investors need risk diversification
• [Steve] The data from negative trial results ought to be made widely available as well.
• Clinical trials tend to "give up too quickly" whenever they encounter negative result #longevity #aging #healthspan #LifeExtension #conferences #medicine

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