RT Journal Article
SR Electronic
T1 Reversing age: dual species measurement of epigenetic age with a single clock
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.07.082917
DO 10.1101/2020.05.07.082917
A1 Steve Horvath
A1 Kavita Singh
A1 Ken Raj
A1 Shraddha Khairnar
A1 Akshay Sanghavi
A1 Agnivesh Shrivastava
A1 Joseph A. Zoller
A1 Caesar Z. Li
A1 Claudia B. Herenu
A1 Martina Canatelli-Mallat
A1 Marianne Lehmann
A1 Leah C. Solberg Woods
A1 Angel Garcia Martinez
A1 Tengfei Wang
A1 Priscila Chiavellini
A1 Andrew J. Levine
A1 Hao Chen
A1 Rodolfo G. Goya
A1 Harold L. Katcher
YR 2020
UL http://biorxiv.org/content/early/2020/05/08/2020.05.07.082917.abstract
AB Young blood plasma is known to confer beneficial effects on various organs in mice. However, it was not known whether young plasma rejuvenates cells and tissues at the epigenetic level; whether it alters the epigenetic clock, which is a highly-accurate molecular biomarker of aging. To address this question, we developed and validated six different epigenetic clocks for rat tissues that are based on DNA methylation values derived from n=593 tissue samples. As indicated by their respective names, the rat pan-tissue clock can be applied to DNA methylation profiles from all rat tissues, while the rat brain-, liver-, and blood clocks apply to the corresponding tissue types. We also developed two epigenetic clocks that apply to both human and rat tissues by adding n=850 human tissue samples to the training data. We employed these six clocks to investigate the rejuvenation effects of a plasma fraction treatment in different rat tissues. The treatment more than halved the epigenetic ages of blood, heart, and liver tissue. A less pronounced, but statistically significant, rejuvenation effect could be observed in the hypothalamus. The treatment was accompanied by progressive improvement in the function of these organs as ascertained through numerous biochemical/physiological biomarkers and behavioral responses to assess cognitive functions. Cellular senescence, which is not associated with epigenetic aging, was also considerably reduced in vital organs. Overall, this study demonstrates that a plasma-derived treatment markedly reverses aging according to epigenetic clocks and benchmark biomarkers of aging.Competing Interest StatementSeveral authors are founders, owners, employees (Harold Katcher and Akshay Sanghavi) or consultants of Nugenics Research (Steve Horvath and Agnivesh Shrivastava) which plans to commercialize the "Elixir" treatment. Other authors (Kavita Singh, Shraddha Khairnar) received financial support from Nugenics Research. The other authors do not have conflict of interest.