Effects of exercise and physical activity on circulating inflammaging- and immunosenescence-related biomarkers in older adults and adults with chronic diseases: an umbrella review

BACKGROUND: Chronic low-grade inflammation and immunosenescence accompany ageing and chronic disease. Exercise and physical activity are proposed to modify circulating inflammatory biomarkers, but review-level evidence is dispersed across populations and conditions. METHODS: We searched PubMed, Web of Science, Embase, Cochrane Library, Scopus, and SPORTDiscus through 1 March 2026 for systematic reviews, meta-analyses, and overviews on exercise or physical activity and circulating inflammaging- or immunosenescence-related biomarkers in older adults and adults with chronic diseases. We reported the review in accordance with PRISMA 2020 and PRIOR. Methodological quality was appraised with A MeaSurement Tool to Assess systematic Reviews, version 2 (AMSTAR-2), primary-study overlap with the corrected covered area, and certainty with GRADE. We performed no de novo meta-analysis or meta-regression; this umbrella review is a structured narrative synthesis of quantitative review-level estimates rather than a quantitative reanalysis. RESULTS: Twenty-one reviews were included: 14 core-eligible (full Population, Intervention, Comparator, Outcomes, and Study design [PICOS] match, contributing to the primary synthesis and conclusions) and seven evidence-map-only (partial PICOS match, used only for mapping and background). Among core-eligible reviews reporting standardised mean differences, exercise was associated with small reductions in tumour necrosis factor-alpha (TNF-alpha; point estimates - 1.42 to - 0.05, two of five confidence intervals excluding the null) and C-reactive protein (CRP; - 0.65 to - 0.47, two of three excluding the null), whereas interleukin-6 (IL-6) estimates were inconsistent (- 0.81 to + 0.09, two of five excluding the null). Heterogeneity was frequently high (I ² up to 94%). Overall primary-study overlap was slight (corrected covered area [CCA] = 0.0091), but very high within the multiple sclerosis cluster (CCA = 0.4048). AMSTAR-2 confidence was critically low in 11 reviews, low in nine, and moderate in one; GRADE certainty was very low for every biomarker construct. A post hoc restricted descriptive sensitivity analysis excluding critically low reviews attenuated the apparent signal. CONCLUSION: Exercise and physical activity may produce small reductions in some circulating inflammatory biomarkers, most consistently TNF-alpha and CRP, but effects on IL-6 are inconsistent, and certainty is very low. Effects on immunosenescence and cellular-senescence markers remain an evidence gap. This biomarker evidence alone is insufficient to justify prescribing exercise specifically to lower inflammatory biomarkers and does not alter broader physical-activity recommendations based on clinical and functional outcomes.PROSPERO: CRD420261410061.