A Blueprint For Radically Open, Citizen Science Approach To Aging Research

Leonid Peshkin, Ph.D., is an unconventional man working at an Ivy League research university in a field he believes is rightfully viewed with “great skepticism” by mainstream biologists. …

The Russian-born Peshkin, who lectures in systems biology at Harvard, wants to make clear he is “not a rotten socialist,” but he does think commercialization in the aging field is killing the science. The great temptation is to form companies that become slave to investors and start hiding the negatives and inflating the positives, he says.

Evidence to date points to two possible ways to extend lifespan and only one of them—the once-obscure immunosuppressive agent rapamycin (sirolimus)—is a pharmaceutical, he says. The other, seemingly more effective remedy is calorie restriction. …

He says he particularly likes one theory, which has yet to be adequately investigated, that rapamycin works by turning on autophagy—the body’s way of cleaning out damaged cells. It’s the same process that gets triggered by intermittent fasting.

Peshkin points to an initiative called the Intervention Testing Program (ITP), a multi-institutional program of the National Institute on Aging for evaluating agents (mostly drugs or nutraceuticals) on the aging process in mice. The program launched in 2004, … is the only study out of the hundreds producing lifespan results that is well designed and properly run, he says.

Peshkin doesn’t believe any one drug is ever going to be a cure-all for healthy aging. Rather, he favors the approach of piecing together clues across many different drugs about the important mechanisms behind slowing the aging process.

Drugs As Questions

In addition to ITP, Peshkin credits Longevica with another laudable if oddball initiative that a decade ago put mice on 1,000 different pharmacological compounds to test the effects, if any, on their lifespan. As announced by the company last year, it plans to launch supplements based on its research suggesting five substances significantly increase longevity—inulin, pentetic acid, clofibrate, Proscillaridin A, and D-Valine—by between 16% and 22%.

Read the full story at the link below:

Related Stories on Leonid Peshkin’s Work:

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Thanks for the list, great article.
Inulin is the only one I’m currently using, feeds my gut buddies and they make it into short chain fatty acids.
Looks like pentetic acid is a chelating agent and can be used to take out heavy metals including iron.
Clofibrate is a lipid lowering agent.
Proscillaridin A is a promising agent to treat glioblastoma. Huh?
D-Valine improves insulin resistance and increases HSC’s.

Is anybody taking D-Valine? How much?

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Yes - the Longevica compounds listed are interesting and I’m generally not very familiar with them. But, yes, I also take Inulin fiber for the short chain fatty acids (SCFA). Here is the product I purchase and use in my smoothies:

Here are some links to get more info on those specific compounds:

Under the leadership of Ryazanov, Longevica says it used 20,000 long-lived female mice and 1,033 drugs representing compounds from 62 pharmacological classes to find five substances that statistically significantly increased longevity by 16-22%: Inulin, Pentetic Acid, Clofibrate, Proscillaridin A, D-Valine.

From this story: Longevity startup Longevica plans to launch supplements based on long-term research

The company website: https://www.longevica.com

The Company filed patent in this area:
Methods and compositions for extending lifespan, Patent Application 20200254006

Inulin

Pentetic acid

https://www.drugs.com/pro/pentetic-acid.html

Clofibrate

Included in this list:

Proscillaridin A

https://www.nature.com/articles/s41467-017-02332-3

D-Valine

Evidence that Intake of L-valine May Affect the Lifespan-specific Local Gene Network Pattern in Caenorhabditis Elegans - PDF file for direct download

From the patent filed;

"This invention also provides a dietary supplement or food or beverage product comprising:

(a) Inulin; and

(b) Lemon or lime extract, DTPA, EDTA, St. John’s wort extract, Hyperforin, Ginkgo bilogoba extract, Ginkgolide A or B, vitamin C, Ascorbic acid 6-palmitate, Pantothenic acid (vitamin B-5), Niacinamide, Allicin (garlic), Lactobionate, Melatonin, Metformin, L-Dopa, extract Mucuna beans (Mucuna Dopa), L-Histidine, Quercetin, Curcumin, L-Glutamic acid, succinic acid, N-Acetil Cysteine, Green tea extract, Epigallocatechin-3-gallaye, Glutathione, Aspirin, Salicylate, Glycine, Resveratrol, Genistein, Garnosine, Rapamycin, Lipoic acid, or Taurine."

Metformin and Rapamycin included.

What is wrong with this picture?

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It seems they are thinking very long term… when rapamycin becomes an “over the counter” drug, or a supplement. :grinning:

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Is that like when the Singapore Government ask Nir Barzilai about putting metformin in the water supply?

From a Nir Barzilai interview.

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The Blueprint link, this one has always boggled my mind.

Cleansing Process

One seemingly “idiotic” question, Peshkin says, illustrates his approach to finding life-extending therapies: “Why are babies born young?” The egg and sperm producing new life have both been around for some time, even if both parents are 20 years old, and mixing them mysteriously undoes the damage of age in the germline. (my bold…Like how does that happen??)

People have been discussing this “germ-line reset” in the context of the “germ-plasm theory” of August Weismann for over 100 years, he adds, but—once again—nobody has ever properly investigated the idea. So, in addition to more rigorously testing anti-aging interventions, Peshkin wants to learn what might be happening very early in the process of oocyte separation and early development to make all the cellular garbage suddenly disappear.

To that end, a new dataset is being produced by mass spectrometry showing what happens to frog oocytes that Peshkin will analyze in search of measurable evidence of a cleansing process that is comparable to what happens during human ovulation. Specifically, he’ll be looking for protein aggregates in the eggs and, if he finds them, see if they disappear during oocyte maturation.

If so, he says, it might shed light on a pre-existing program in the genome that could be activated in adult cells to undo some of the damage of aging in various body tissues.

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