The Effect of longevity interventions on epigenetic clocks (BioRxiv)

This is is interesting… why would rapamycin, the best longevity agent out there, not show an impact?

From David Sinclair’s twitter feed - a series of posts: x.com

DNA methylation (DNAme) age reductions. Red asterisks represent statistical significance

  • P<0.05; ** 0.01; *** 0.001

Blood biomarkers that serve as proxies for DNAme age and diets:

CystatinC - kidney function
HBA1c - glucose / diabetes
CRP - inflammation/ heart disease
ALK - liver / bone health
Triglycerides - serum fat / heart disease

Open Access Preprint Paper:

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Ah - perhaps we have an answer:

Source: x.com

And some other thoughts by Kamil Pabis, Geroscience researcher a the University of Singapore:

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So I should start Remicade and kidney dialysis? My brother has Crohns and is on Remicade. That stuff is expensive, he somehow got it through insurance.

I don’t know my epigenetic age. I wonder how many people on here do?

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think that one is statically increasing epi age?

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Oops, thanks. I should have looked a little longer.

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A transplant is in the improvement list which is probably true for people who need it. What would be interesting is to know the results from no intervention

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My father, who is one of the healthiest people I know, took the Tally Health Epigenetic Age test, and it came back much higher than his age. The same happened to me with an epigenetic test. I don’t think these tests are useful or accurate at this point. (Although Rapamycin did take 7 years off my epigenetic age.) OTOH, the Levine calculator consistently says I’m 10 years younger than my age. Which is better science? Epigenetics or Biomarkers? In my case, these two tell vastly different stories.

I think I’ll trust the biomarkers.

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All of the systems have their problems. I think a mixture of krebs metabolites and pH in serum might give some ideas, but I would need to get a good subset of data and work on those. These things are not readily available.

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@John_Hemming Are there ways people can participate / volunteer in some of the things you are studying to speed your learnings up?

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I welcome anyone who wishes to get involved. I am putting together a team for the XPRIZE which will be part of this, but if people are interested in running the same sort of testing even outside the XPRIZE I would welcome that.

One problem with the sort of things I do is that the testing can be quite expensive. Full panel blood draws twice a week is not cheap.

To get somewhere with the above testing is a bit difficult because I first need to find a lab capable of doing the tests.

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Feedback from David Barzilai on this new preprint paper:

and comments from Max Unfried, longevity researcher at National University of Singapore:

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DeStrider : I think I’ll trust the biomarkers.

Me too. I’ll choose biomarkers and functional physical and mental tests over methylation clocks any time. Even the “third-generation” clocks may be dubious. I did Dunedin Pace, measuring the rate of aging, twice not far apart. The differences were too big to be trustworthy.

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A scientific showdown seeks the biological ‘clock’ that best tracks aging

A contest with $300,000 in prize money aims to improve molecular assays needed to test aging treatments

Some people like to say that age is just a number. Many scientists increasingly agree, arguing that DNA, protein, or other molecular measurements can tell a truer story about a person’s “biological” age than what’s on their birth certificate. Hundreds of so-called aging clocks developed in recent years reflect this idea, and clinical trials have started to use them to assess patients’ responses to putative antiaging treatments. Numerous wellness clinics now claim they can—for a steep price—deduce a person’s actual age, and multiple companies offer biological age testing for worried patients—and even for their dogs.

But scientists don’t agree on which aging clocks work best or how to verify their results. “We need to systematically evaluate them,” says bioinformatician Mahdi Moqri of Harvard Medical School. That’s the motivation for an unprecedented contest, funded by nonprofits and philanthropies and run by an organization called the Biomarkers of Aging Consortium, that is pitting hundreds of the clocks against one another for scientific honors—and some $300,000 in prize money.

Drawing on anonymized data and health information for 500 people, the competitors are vying to produce the most accurate predictions of chronological age, age at death, and “health span”—the time until onset of multiple age-related diseases. “The competition is put up or shut up” for clockmakers, says biogerontologist Steve Horvath of the cell rejuvenation firm Altos Labs, who developed a DNA-based aging assay that kick-started the field more than a decade ago.

https://www.science.org/content/article/scientific-showdown-seeks-biological-clock-best-tracks-aging

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their category of IF/CR seems poorly defined. Calorie restriction, without going too far, is the most sure way to increase maximum lifespan.

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What are people’s thoughts on HBOT?

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  • exercise - while it clearly improves healthspan and health state and probably decreases mortality, does not generally have support in the literature extending lifespan or longevity, so that one might actually be as we’d expect based on other geoscience literature

@Neo I think HBOT is a double edged sword. Extra oxygen sounds helpful when there is poor blood / oxygen circulation and a persistent infection or a poorly healing wound. But extra oxygen for the heck of it sounds dangerous from an oxidation point of view. What good could come of it? I’d rather go for low oxygen training.

Am I missing something?

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@Joseph_Lavelle Yeah, I’ve been wary about it, but it keeps coming up in many contexts, so thought might be worth some discussion with any people who have been thinking about it.

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Its interesting, but most of the longevity / telomerase research and HBOT seems to be coming out of a single lab in Israel, where they also commercialize it (so not exactly unbiased in their research). We’ve discussed it in the past a bit here: Hyperbaric Oxygen Therapy

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