Researchers here suggest that exercise interventions affect the turnover rate of senescent cells in older people, mostly likely by both reducing the pace at which cells become senescent, and improving the pace of clearance by the immune system. The size of the effect is modest, as one might expect, given that exercise cannot hold a candle to the benefits produced by senolytic drugs when it comes to reversing measures of aging in mice. This and other recent evidence increasingly suggests that individual senescent cells do not linger for very long in the body in later life. The observed accumulation with age is instead the outcome of a progressively growing imbalance between mechanisms of creation and mechanisms of destruction.
Cellular senescence has emerged as a significant and potentially tractable mechanism of aging and multiple aging-related conditions. Biomarkers of senescent cell burden, including molecular signals in circulating immune cells and the abundance of circulating senescence-related proteins, have been associated with chronological age and clinical parameters of biological age in humans. The extent to which senescence biomarkers are affected by interventions that enhance health and function has not yet been examined.
Here, we report that a 12-week structured exercise program drives significant improvements in several performance-based and self-reported measures of physical function in older adults. Impressively, the expression of key markers of the senescence program, including p16, p21, cGAS, and TNFα, were significantly lowered in CD3+ T cells in response to the intervention, as were the circulating concentrations of multiple senescence-related proteins. Moreover, partial least squares discriminant analysis showed levels of senescence-related proteins at baseline were predictive of changes in physical function in response to the exercise intervention.
Our study provides first-in-human evidence that biomarkers of senescent cell burden are significantly lowered by a structured exercise program and predictive of the adaptive response to exercise.