Evidence gaps in the effects of exercise on SASP-Related biomarkers in older adults: a systematic review and meta-analysis of randomized controlled trials

Cellular senescence is a hallmark of aging, characterized by the secretion of proinflammatory factors known as the senescence-associated secretory phenotype (SASP). While physical exercise is proposed as a potential modulator of cellular aging, its effect on specific senescence biomarkers in older adults remains unclear. We conducted a systematic review and meta-analysis following PRISMA guidelines (PROSPERO: CRD42024623676). Randomized controlled trials (RCTs) involving participants aged ≥ 60 years were included if they compared structured exercise interventions with control conditions and reported biomarkers of cellular senescence. A Bayesian meta-analysis was performed, and the risk of bias was assessed using the Cochrane RoB 2.0 tool. Three RCTs (n = 1447; age range 66–79; 64.2% female) met the inclusion criteria. Two were eligible for meta-analysis, focusing on SASP-related cytokines (CCL2, IL-6, IL-8, TNF-α). No statistically significant differences were observed between the exercise and control groups. One excluded study reported increased SIRT levels following resistance training, but these are not standard senescence markers. Notably, none of the included RCTs evaluated key upstream markers such as p16^INK4a^ or p21, highlighting a critical gap in current research. This review found no conclusive evidence that exercise training affects canonical markers of cellular senescence in older adults. The biomarkers analyzed were limited to SASP-related cytokines, which reflect downstream inflammation rather than primary senescence regulation. Future studies should use standardized protocols to evaluate upstream markers such as p16^INK4a^ and p21 to better understand the impact of physical activity on cellular aging.