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Rapamycin retards epigenetic aging of keratinocytes

The age-retarding effects of rapamycin--previously demonstrated in animal models--has been replicated in cultured human cells, according to findings published in Aging (May 26, 2019;11(10):3238-3249).

Dr. Steve Horvath at UCLA in tandem with Dr. Ken Raj of Public Health England generated an algorithm called the skin and blood clock, which is applicable to cultured cells as well as those in the body. By using this epigenetic clock, the doctors demonstrate that rapamycin's retardation of aging extends to human cells.

Though the research has been conducted on human cells, and not the body, the finding is consistent with the independent observation that a variant of the MLST8 gene, which encodes part of the target of rapamycin, is linked with increased rate of epigenetic aging in humans.

The convergence between observations from the bench using cultured cells, and genome-wide association studies with human tissues, highlight the fidelity of this system, which has been derived and validated in humans, to test the effects of compounds on human aging.

Also of note is the fact that rapamycin has been well-documented to prevent arrested cells from becoming senescent - a process known as gero-conversion, which Drs. Raj and Horvath have previously demonstrated to be distinct from epigenetic aging.

"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 and epigenetic aging, with the possibility of augmentation of cellular proliferative potential," The Raj research team concluded.

It appears that rapamycin possesses the ability to inhibit not one, but two-independent pathways of aging. This two-for-one type finding is rare in biology.

However, the researchers say it is important to understand that the effect of rapamycin has yet to be widely tested on other cells types. Despite the caveat, Drs. Horvath and Raj believe this finding and the available tools and methods can encourage the search for even better compounds that may help in promoting healthy human aging.

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