Current Aging Clocks are Arguably Too Sensitive to Transient Stresses
Numerous clocks to assess biological age have been constructed based on comparisons of epigenetic, transcriptomic, proteomic, and other data that changes with age. When measured using white blood cells from a blood sample, one might argue that these clocks are overly influenced by the state of the immune system, changing in response to circumstances. With that in mind, researchers here report on the tendency of measured biological age to transiently increase during stressful circumstances. Aging clocks exhibit a range of other quirks, such as the noted insensitivity to physical fitness in early epigenetic clocks, and there is clearly a great deal more work to be accomplished if clocks are to become trusted enough to be used to assess the potential of new approaches to rejuvenation, and thereby guide the direction of research and development.
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.
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 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. The elevation of biological age by stress may be a quantifiable and actionable target for future interventions.