Biological age is increased by stress and restored upon recovery

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 pos-sibility of age reversal. Here, we report that biological age is fluid and exhibits rapid changes in both direc-tions. At epigenetic, transcriptomic, and metabolomic levels, we find that the biological age of young mice is increased by heterochronic parabiosis and restored following surgical detachment. We also identify tran-sient 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. The elevation of biological age by stress may be a quantifiable and actionable target for future interventions.

Automated summary

Aging is traditionally seen as a steady process of accumulating damage and loss of function, but recent studies have suggested the possibility of age reversal. This study found that biological age can change rapidly in response to different stressors, including surgery, pregnancy, and severe COVID-19. The elevation of biological age by stress is reversible, indicating that it is a dynamic process. Understanding the dynamics of aging can inform future interventions targeted at reducing stress-induced aging.