Moderate-vigorous physical activity attenuates premature senescence of immune cells in sedentary adults with obesity: a pilot randomized controlled trial

Despite the well-known senolytic effects of physical exercise on immune cells in older adults, the effect of physical activity (PA) on premature immune senescence in sedentary adults with obesity remains largely unknown. This pilot study aimed to investigate the role of objectively measured physical behaviors and Fitbit watch-based free-living PA intervention in premature senescence of immune cells in sedentary adults with obesity. Forty-five participants were recruited in the cross-sectional analysis, and forty of them further participated in the randomized controlled trial. We found that objectively measured moderate-vigorous PA was independently and inversely correlated with the expression of p16(INK4a) and p21(Cip1) in the peripheral blood mononuclear cell (PBMCs) of adults with obesity; however, chronological age, body mass index, body fat, maximal oxygen consumption, light PA, sedentary behaviors, and sleep duration were not. More importantly, the 12-week PA intervention mitigated the elevated p16(INK4a) levels in PBMCs, though it showed no effect on p21(Cip1) and senescence-associated secretory phenotypes. Taken together, physical inactivity is an independent determinant of premature senescence in immune cells, while the 12-week PA intervention is a promising strategy to alleviate premature immune senescence in adults with obesity.