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[Mind]

LongeCity was happy to sponsor EARD 2023 in New York and have a representative attend on its behalf.

 

Attached is a review and report about the conference from Dr. John Furber

Attached Files

•  EARD2023-Report John Furber.pdf   556.46KB   134 downloads

[JohnFurber]

Ending Age Related Diseases:  Longevity+DeSci Summit NYC

organized by the Lifespan Extension Advocacy Foundation, which is also called "LEAF" or "Lifespan.io".

New York City, 10 - 11 August 2023

Additional comments by John D. Furber

There was a variety of backgrounds among the speakers and the panelists, as well as among the audience. There were scientists and professors who study and teach the biology of aging, rejuvenation, and pharmaceutical development. There were entrepreneurs with business backgrounds. There were venture capitalists. 

Some of the speakers and attendees are regulars at longevity conferences around the globe. It is good to see them in person, and to get updates on their recent progress.
The organizers kept the sessions on schedule. At times, I found it difficult to decide between a session in the main auditorium, and a panel in the smaller upstairs hall.
Even at the end of each day, conversations continued on the front steps of the building.
You might see some familiar faces among the photos at https://www.lifespan...iseases-photos/

I asked Vadim Gladyshev about the hypothesis that transposons might be a cause of increasing damage to the genome with increasing age. He replied that that this is a hypothesis worth further study. He suggested talking about this with John Sedivy and Vera Gorbunova.

Although not a speaker, Dr. Callahan from the FDA was in the audience. I asked him about what would be required to bring to market a drug candidate that had been developed more than 20 years ago by a company that has since gone out of business. The patent has expired.
He explained that if a new company brings back a drug with an expired patent, and qualifies it for a new indication, the new company can have 5 years of exclusive marketing of that drug.
He suggested some information resources online:
inxight drugs     
drugs.ncats.io   
ncats.io   NIH National Center for Advancing Translational Sciences
"At NCATS, we tackle ongoing challenges in research so that new treatments can reach people faster. We focus on what is common across diseases and develop solutions that reduce, remove or bypass bottlenecks in the translational process. Our vision is more treatments for all people more quickly. Learn more about the Center below or visit our fact sheets page for more details about Center activities."

 

 

[JohnFurber]

Ending Age Related Diseases:  Longevity+DeSci Summit NYC

organized by the Lifespan Extension Advocacy Foundation, which is also called "LEAF" or "Lifespan.io".

New York City, 10 - 11 August 2023

 

Additional comments #2 by John D. Furber

 

I re-watched the video recording of Dr. Brian Kennedy's Keynote. Here are my extended notes which update the notes on page 10 of the PDF report that is posted above:

 

Keynote:   An International Perspective on Human Longevity Trials, Aging, and DeSci.

Brian Kennedy PhD,

National University of Singapore - Director of the Centre for Healthy Longevity

Dr. Brian Kennedy discusses progress in human longevity trials and gives an international perspective to the fight against age-related disease.
The NUS Medical School has long had the slogan "First, Do no harm." But Brian tells them that “doing nothing” is harmful. (applause).
Interventions are important. But also, we need to learn the fundamental biology of healthy longevity.
 
We need Biomarkers so we can assess what is working.
We also need interventions. Actually, there are quite a few interventions that have been reported to modify aging in animal models.
https://genomics.sen...nce.info/drugs/
Can we extend human healthspan and maximum lifespan?
In our lab, we are conducting animal tests on:
 alpha Keto-butyrate, alpha Keto-Glutarate, Ergothioneine, Fisetin, Gemfibrozil, Glycine, NR/NMN, NSAIDs, Rapamycin, Spermidine, Urolithin A, Vitamin A, and Vitamin D.
From the list above, the following have produced promising results in our lab:
αKeto-Glutarate, Gemfibrozil, Glycine, Rapamycin, Spermidine, Urolithin A, Vitamin A, and Vitamin D.
 We are especially interested in αKeto-Glutarate and in Gemfibrozil.
Taurine (Velagapudi, Ali, Yadav 2012) (Singh, Kennedy, Yadiv, et.al. Science 2023) can alter lifespan in mice.
Human levels of Taurine in their blood serum decline with age. We plan to collaborate with the Yadiv lab on some studies in the near future.  Taurine interacts with cysteine to beneficially affect stem cells, autophagy, DNA damage, epigenetic changes, and other things.
 
The phrases "Hallmarks of Aging" and "Pillars of Aging" can be misleading. Those written about are often downstream of the actual primary causes of aging.
We want to find the actual targets of the small molecules that are yielding results.
 
Mouse biomarkers: We are doing 8 month studies on mice with measurements every 2 months between 20 and 28 months of age: Frailty, complete blood count (CBC), Senescence, fluorescence activated cell sorting (FACS), grip strength, rotarod time, treadmill endurance, Barnes maze performance.
Males and Females age differently.
For any experimental therapy, we need to test a variety of doses.
Gemfibrozil: (Lopid.  off-patent) In old mice, it reduces amino acid uptake, and reduced frailty by about 45%. Its target is NOT PPARα (which others had previously reported).  Chong He has studied this at the Buck Institute.
They used a Thermal Shift Assay to find what it binds to. The target of Gemfibrozil seems to be PEPT1, which takes amino acids from the small intestine into the body.
It reduces amino acid absorption, similar to dietary restriction.
We note that restricting amino acids is effective for increasing lifespan, perhaps related to reducing mTOR signaling.
Gemfibrozil has 2 other target involved in lipid metabolism.
Urolithin A is also reducing frailty in old mice.
They are starting a company "to make old drugs young again." Now that they have found a correct target, they can make better derivative molecules that affect these targets.  Maybe 20% of all drugs on the market have mis-identified their target.
 
Ponce de Leon Health company (PDL) is selling sustained-release calcium-alpha-keto-glutarate (Ca-αKG). 
(Shahmirzadi, et.al. Cell Metabolism 2020, 32:447-456)
People taking it for 7 months had a 7 year reduction in their epigenetic age, as reported by the TruAge company.
(Demidenko, et al, Aging 2021, In press)
We noticed that people that were biologically younger than their chronologic age have very little response, but people who were biologically older than their chronologic age, had a robust response, and got biologically younger.
At NUS, they are accepting human trial subjects for Ca-αKG intervention who are older than their biologic age. They are accepting people in their 40s, 50s, and 60s that are reasonably healthy, but not people that dramatically biologically younger.
Kennedy suggests that an older subject, seeking to reverse muscle loss, would take 1 gram/day of sustained-release Ca-αKG, in addition to increasing resistance exercise.
How do we combine interventions? We don't really know.
Which aging clocks are best?
They have a weekly series of online lectures on aging research, which anyone can watch for free. (Weds 7pm Singapore time)
Their NUS talks are all available for viewing live from NUS, or later as recordings on their Youtube channel.
Urolithin-A (from pomegranate juice) reduces frailty in male mice. It extends the lifespan of killifish.
 
Q (John Furber): When I go online, looking for Ca-αKG, I find Arg-αKG for 1/10 the cost. Is there a market or technical reason for this?
A (Kennedy): The Ca-αKG by PDL is a time-release formulation. We think that it is important to affect the gut in a time-release manner because αKG strengthens the mucosal layer of the large intestine. So the time-release formulation is more likely to make it through digestive system all the way to the large intestine. But actually, we have not tested Arg-αKG, so we don't know how well it compares with Ca-αKG.
 
[Furber calculates that, based upon their different molecular weights, 1 gram of Ca-αKG contains 785 mg of αKG. This much αKG is contained in 1.72 grams of Arg-αKG. Perhaps taking several divided doses throughout the day might give results similar to a sustained-release formulation, but maybe not. If divided into 4 doses, that would be 430 mg Arg-αKG per dose, 4 times per day.]