Rapamycin retards epigenetic ageing
This is very good news.
The advent of epigenetic clocks has prompted questions about the place of epigenetic ageing within the current understanding of ageing biology. It was hitherto unclear whether epigenetic ageing represents a distinct mode of ageing or a manifestation of a known characteristic of ageing. We report here that epigenetic ageing is not affected by replicative senescence, telomere length, somatic cell differentiation, cellular proliferation rate or frequency. It is instead retarded by rapamycin, the potent inhibitor of the mTOR complex which governs many pathways relating to cellular metabolism. Rapamycin, however, is also an effective inhibitor of cellular senescence. Hence cellular metabolism underlies two independent arms of ageing – cellular senescence and epigenetic ageing. The demonstration that a compound that targets metabolism can slow epigenetic ageing provides a long-awaited point-of-entry into elucidating the molecular pathways that underpin the latter. Lastly, we report here an in vitro assay, validated in humans, that recapitulates human epigenetic ageing that can be used to investigate and identify potential interventions that can inhibit or retard it.
In summary, the observations above represent the first biological connection between epigenetic ageing and rapamycin. These results for human cells add to the evidence that extension of life, at least by rapamycin, is indeed accompanied by retardation of ageing. These observations also suggest that the life-extending property of rapamycin may be a resultant of its multiple actions which include, but not necessarily limited to suppression of cellular senescence [36–38,48] and epigenetic aging, with the possibility of augmentation of cellular proliferative potential.