PT  - JOURNAL ARTICLE
AU  - Andrei E. Tarkhov
AU  - Kirill A. Denisov
AU  - Peter O. Fedichev
TI  - Aging clocks, entropy, and the limits of age-reversal
AID  - 10.1101/2022.02.06.479300
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.02.06.479300
4099  - http://biorxiv.org/content/early/2022/02/09/2022.02.06.479300.short
4100  - http://biorxiv.org/content/early/2022/02/09/2022.02.06.479300.full
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.