Data Sheet 1_Effects of exercise and physical activity on circulating inflammaging- and immunosenescence-related biomarkers in older adults and adults with chronic diseases: an umbrella review.docx

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 (I² 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.</p>Conclusion<p>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</p>