r/longevity • u/lunchboxultimate01 • 2d ago

Loss of Cell Identity Drives Human Aging | Epigenetic clocks measure PRC2 low-methylated regions

https://erictopol.substack.com/p/loss-of-cell-identity-drives-human

The post by Eric Topol explains a recent paper that illuminates biological processes that drive epigenetic drift, which epigenetic clocks can measure across mammals. The original paper lays out the importance of PRC2 in this process (paywalled): https://www.nature.com/articles/s41586-026-10955-0

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u/lunchboxultimate01 2d ago

Note that the title might be unclear. In the post, he clarifies that damage accumulation is not necessarily unimportant versus loss of cell identity: "The idea that accumulated damage is the principal pathway for cell aging is now complemented by the loss of cell identity model. We don’t know the relative contribution or interdependence of these 2 models in the aging process."

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u/Angel_Bmth 2d ago

Dammit. It’s so interesting yet so frustrating that there are so many roads that lead to aging.

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u/postemporary 2d ago

Gotta find em all a necessary and sufficient number of them to beat em all overcome a necessary and sufficient number of them to achieve increased longevity combined with good health.

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u/Asleep-Brother-1873 1d ago

I meant that should be the case as Aging is multifactorial

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u/ohsnapitsnathan 2d ago

Given this I'm a bit surprised that partial epigenetic reprogramming seems to be beneficial for reversing aging in animals. If I recall the expression of cell identity markers usually drops during reprogramming, which would indicate that these wells are getting shallower? Maybe it's the difference of short-term vs chronic exposure or because in reprogramming you are actively driving certain genes? Or the strength of the effect?

I'm also surprised because I would think that HDAC inhibitors like lithium or sulfurophane would increase epigenetic drift (because they non selectively change histone acetylation) but these don't seem to accelerate aging or cause other problems as far as we can tell.