Reversal of epigenetic aging and immunosenescent trends in humans

• Published in: Aging cell Vol. 18; no. 6; pp. e13028 - n/a
• Main Authors: Fahy, Gregory M., Brooke, Robert T., Watson, James P., Good, Zinaida, Vasanawala, Shreyas S., Maecker, Holden, Leipold, Michael D., Lin, David T. S., Kobor, Michael S., Horvath, Steve
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.12.2019; John Wiley and Sons Inc
• Subjects: Age; Aged; Aging; Aging - genetics; c-reactive protein; Epigenesis, Genetic - genetics; Epigenetic inheritance; Epigenetics; Healthy Volunteers; Humans; Immunosenescence; Life span; Longevity; lymphocyte‐to‐monocyte ratio; Male; Middle Aged; Morbidity; naive T cells; Original; PD‐1; PSA; thymic regeneration; naive T cells; thymic regeneration; PD-1; lymphocyte-to-monocyte ratio; c-reactive protein; PSA
• ISSN: 1474-9718; 1474-9726
• DOI: 10.1111/acel.13028

Epigenetic “clocks” can now surpass chronological age in accuracy for estimating biological age. Here, we use four such age estimators to show that epigenetic aging can be reversed in humans. Using a protocol intended to regenerate the thymus, we observed protective immunological changes, improved risk indices for many age‐related diseases, and a mean epigenetic age approximately 1.5 years less than baseline after 1 year of treatment (−2.5‐year change compared to no treatment at the end of the study). The rate of epigenetic aging reversal relative to chronological age accelerated from −1.6 year/year from 0–9 month to −6.5 year/year from 9–12 month. The GrimAge predictor of human morbidity and mortality showed a 2‐year decrease in epigenetic vs. chronological age that persisted six months after discontinuing treatment. This is to our knowledge the first report of an increase, based on an epigenetic age estimator, in predicted human lifespan by means of a currently accessible aging intervention. Epigenetic aging—an accurate measure of biological aging in humans—can run in reverse. A thymus regeneration protocol has enabled estimated biological age to decrease in healthy 51‐ to 65‐year‐old men by 1.5 years after 1 year of treatment (or by 2.5 years compared to chronological age). This significantly exceeds the heretofore theoretical concept of “longevity escape velocity,” wherein biological age is reduced by 1 year for every 1 year of chronological age.