Biological age is increased by stress and restored upon recovery

Jesse R. Poganik; Bohan Zhang; Gurpreet Singh Baht; Alexander Tyshkovskiy; Amy Deik; Csaba Kerepesi; Sun Hee Yim; Ake Tzu-Hui Lu; Amin Haghani; Tong Gong; Anna M. Hedman; Ellika G. Andolf; Göran Pershagen; Catarina Almqvist; Clary B. Clish; Steve Horvath; James P. White; Vadim N. Gladyshev

doi:10.1016/j.cmet.2023.03.015

Systems BiologyCell MetabolismApr 21, 2023

Peer-reviewed journal article

Biological age is increased by stress and restored upon recovery

Jesse R. Poganik iD, Bohan Zhang iD, Gurpreet Singh Baht iD, Alexander Tyshkovskiy iD, Amy Deik iD, Csaba Kerepesi iD, Sun Hee Yim iD, Ake Tzu-Hui Lu iD, Amin Haghani iD, Tong Gong iD, Anna M. Hedman iD, Ellika G. Andolf iD, Göran Pershagen iD, Catarina Almqvist iD, Clary B. Clish iD, Steve Horvath iD, James P. White iD, Vadim N. Gladyshev iD

Abstract

Aging is classically conceptualized as an ever-increasing trajectory of damage accumulation and loss of function, leading to increases in morbidity and mortality. However, recent in vitro studies have raised the possibility of age reversal. Here, we report that biological age is fluid and exhibits rapid changes in both directions. By applying advanced epigenetic aging clocks, we find that the biological age of young mice is increased by heterochronic parabiosis and restored following surgical detachment of animals. We also identify transient changes in biological age during major surgery, pregnancy, and severe COVID-19 in humans and/or mice. Together, these data show that biological age undergoes a rapid increase in response to diverse forms of stress, which is reversed following recovery from stress. Our study uncovers a new layer of aging dynamics that should be considered in future studies. Elevation of biological age by stress may be a quantifiable and actionable target for future interventions.

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