BACKGROUND AND OBJECTIVES: Physical exercise is widely recognized as an effective non-pharmacological intervention that improves not only functional capacity, but also cognition and quality of life in older adults. However, the molecular pathways through which it influences aging-related processes remain incompletely understood. This systematic review and meta-analysis aimed to synthesize current evidence on the effects of structured physical exercise intervention on molecular biomarkers associated with inflammation and oxidative stress in older adults. RESEARCH DESIGN AND METHODS: Randomized controlled trials which included participants ≥65 years old were identified through searches of PubMed, Scopus, Web of Science, CINAHL, and the Cochrane Library. RESULTS: A total of 50 reports (4,379 participants) were included in the qualitative synthesis, and 38 of them in the different meta-analyses performed. Exercise interventions ranged from 8 weeks to 12 months and included aerobic, resistance, and multicomponent training. Pooled analyses indicated modest but significant reductions in C-Reactive Protein (CRP) and high-sensitivity CRP, as well as increases in IL-10. Effects on other pro-inflammatory cytokines, including IL-6 and TNF-α, were inconsistent across studies. Evidence from a limited number of trials (n = 6) also suggested improvements in redox balance. DISCUSSION AND IMPLICATIONS: Overall, structured physical exercise demonstrates a moderate immunomodulatory and antioxidant effect in older adults, although bias was moderate to high. PROSPERO registry: CRD420251006248.
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