RT Journal Article
SR Electronic
T1 Aging clocks, entropy, and the limits of age-reversal
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.02.06.479300
DO 10.1101/2022.02.06.479300
A1 Andrei E. Tarkhov
A1 Kirill A. Denisov
A1 Peter O. Fedichev
YR 2022
UL http://biorxiv.org/content/early/2022/02/09/2022.02.06.479300.abstract
AB We analyze aging signatures in the DNA-methylation and Electronic Medical Records from the UK Biobank datasets and observe that aging is driven by a large number of individually rare and independent transitions between metastable states in a vast configuration space. The compound effect of the configuration changes can be captured by a single stochastic variable, the thermodynamic biological age (tBA), tracking the entropy produced and hence the information lost in the aging process. We show that tBA increases with age, causes the linear aging drift of physiological state variables, reduces resilience, and drives the exponential acceleration of the risks of chronic diseases and death. The entropic character of the aging drift sets limits on possibilities of age-reversal. However, the universal features of configuration transitions suggest practical ways of controlling the rate of aging and thus promising the strongest possible life-extension effects.Competing Interest StatementP.O.F. is a shareholder of Gero PTE. A.E.T., K.A.D., and P.O.F. were employed by Gero PTE during the work on the manuscript. The study was funded by Gero PTE.