Exercise Counters the Age-related Accumulation of Senescent Cells

Xu Zhang; Davis A. Englund; Zaira Aversa; Sarah K. Jachim; Thomas A. White; Nathan K. LeBrasseur


Exerc Sport Sci Rev. 2022;50(4):213-221. 

In This Article

Abstract and Introduction


We propose the beneficial effects of exercise are in part mediated through the prevention and elimination of senescent cells. Exercise counters multiple forms of age-related molecular damage that initiate the senescence program and activates immune cells responsible for senescent cell clearance. Preclinical and clinical evidence for exercise as a senescence-targeting therapy and areas needing further investigation are discussed.


Aging has long been appreciated as the major risk factor for conditions and diseases affecting the cardiovascular, musculoskeletal, central nervous, immune, pulmonary, and other systems. However, until recently, targeting aging to thwart chronic disease, multimorbidity, or geriatric syndromes was viewed as science fiction. Fundamental advances in understanding the biology of aging and proof-of-concept studies in preclinical models have radically changed this perspective and provided a foundation for the new and rapidly expanding field of geroscience.

The geroscience hypothesis posits that interventions that target key hallmarks of aging potentially can prevent, delay, or even reverse age-related conditions as a group.[1] If successful, the impact on human health would be transformative, in terms of both sociomedical costs and quality of life, through extending healthspan, the number of healthy and active years of life, and compressing the period of morbidity to the very end.

The promise of geroscience has resulted in extraordinary public and private investment into pharmacological approaches to counter the effects of aging. Although exhilarating, the profound effects of lifestyle factors on healthy aging should not be overlooked. Exercise, in particular, is a highly effective means to counter the onset and progression of the most prevalent and disabling aging-related conditions, including heart disease, diabetes, Alzheimer disease, osteoporosis, sarcopenia, cancer, and frailty. The effects of exercise on the fundamental mechanisms of aging warrant investigation and may yield new insights into behavioral strategies, pharmacological approaches, and combinations thereof to optimize health and function over the life course.

Over the past decade, mounting evidence highlights cellular senescence, a cell fate in response to diverse forms of molecular and cellular damage, as a driver of aging and aging-related conditions. Moreover, candidate drugs (senotherapeutics) that impact the abundance (senolytics) or behavior (senomorphics) of senescent cells have been shown to counter multiple conditions across multiple physiological systems in mouse models of aging and disease.[2] Herein, we discuss the current evidence supporting that exercise, in part, acts as a senotherapeutic and discuss the future work necessary to gain a fundamental understanding for how exercise directly exerts senotherapeutic effects.