Biomarkers of Cellular Senescence Predict the Onset of Mobility Disability and are Reduced by Physical Activity in Older Adults.

Studies in mice and cross-sectional studies in humans support the premise that cellular senescence is a contributing mechanism to age-associated deficits in physical function. We tested the hypotheses that circulating proteins secreted by senescent cells are i) associated with the incidence of major mobility disability (MMD), the development of persistent mobility disability (PMMD), and decrements in physical functioning in older adults, and ii) influenced by physical activity. Using samples and data obtained longitudinally from the Lifestyle Interventions for Elders (LIFE) Study clinical trial, we measured a panel of 27 proteins secreted by senescent cells. Among 1,377 women and men randomized to either a structured physical activity intervention (PA) or a healthy aging intervention (HA), we observed significant associations between several senescence biomarkers, most distinctly VEGFA, TNFR1, and MMP7, and the onset of both MMD and PMMD. Moreover, VEGFA, GDF15, osteopontin, and other senescence biomarkers were associated with reductions in short physical performance battery scores. The change in senescence biomarkers did not differ between PA and HA participants. In the whole cohort, higher levels of physical activity were associated with significantly greater reductions in 10 senescence-related proteins at 12 and/or 24 months. These data reinforce cellular senescence as a contributing mechanism of age-associated functional decline and the potential for physical activity to attenuate this hallmark of aging.