Exercise Prevents Diet-induced Cellular Senescence in Adipose Tissue

Considerable evidence implicates cellular senescence in the biology of aging and chronic disease. Diet and exercise are determinants of healthy aging; however, the extent to which they affect the behavior and accretion of senescent cells within distinct tissues is not clear. Here we tested the hypothesis that exercise prevents premature senescent cell accumulation and systemic metabolic dysfunction induced by a fast food diet (FFD). Using transgenic mice that express enhanced green fluorescent protein (EGFP) in response to activation of the senescence-associated p16INK4a promoter, we demonstrate that FFD consumption causes deleterious changes in body weight and composition, as well as measures of physical, cardiac, and metabolic health. The harmful effects of the FFD were associated with dramatic increases in several markers of senescence, including p16, EGFP, senescence-associated β-galactosidase, and the senescence-associated secretory phenotype (SASP), specifically in visceral adipose tissue. We show that exercise prevents both the accumulation of senescent cells and the expression of the SASP, while nullifying the damaging effects of the FFD on parameters of health. We also demonstrate that exercise initiated following long-term FFD-feeding reduces senescent phenotype makers in visceral adipose while attenuating physical impairments, suggesting that exercise may provide restorative benefit by mitigating accrued senescent burden. These findings highlight a novel mechanism by which exercise mediates its beneficial effects and reinforce the impact of modifiable lifestyle choices on healthspan.