Exercise-induced changes in circulatory aging-related biomarkers among older adults: longitudinal analysis of a multi-stage randomized clinical trial

Long-term trials evaluating exercise’s impact on systemic aging biomarker profiles in older populations remain limited, particularly regarding multi-component exercise (MCE)-the modality prioritized in the WHO’s 2020 physical activity guidelines. The original study prospectively enrolled well-functioning old adults aged 65 to 85 years. Participants were randomly assigned to a center-based MCE intervention group or a control group. Serum samples were collected at baseline, year 1, year 2, and year 3. Circulatory aging-related biomarkers were measured using a 48-plex cytokine screening technique and enzyme-linked immunosorbent assays. A total of 161 participants were included (87 MCE, 74 control), with mean ages of 73.48 ± 4.56 and 73.24 ± 4.11 years, respectively. At the 1-year follow-up, the MCE group showed greater improvement in physical function, demonstrated by a larger reduction in five-times sit-to-stand test time (-1.27 ± 1.65 vs. -0.56 ± 1.89 s, p = 0.012). Compared to the control group, the decrease of SDF-1α and SCGF-β was attenuated in the MCE group (mean relative increase: 0.09, p = 0.004; mean relative increase: 0.13, p = 0.048, respectively). Whereas, the MCE group showed a greater decrease of G-CSF and a smaller increase of IL-9 than controls (mean relative decrease: −0.19, p = 0.017; mean relative decrease: −0.17, p = 0.005, respectively). Linear regression modeling over a 3-year follow-up identified SDF-1α, TNF-β, SCGF-β, GRO-α, PDGF-BB, and IL-16 as MCE biomarkers with significantly positive trajectories (all p < 0.005), while IL-9 was highlighted as a negatively altered MCE biomarker (p < 0.005). Within the MCE group, the levels of TNF-β, SDF-1α, SCGF-β, IL-12, and IL-2Rα were consistently and positively correlated with exercise frequency, whereas IL-9 levels were negatively associated. Long-term MCE preserved age-related declines in SDF-1α and SCGF-β while attenuating elevations of IL-9 in older adults.