Effects of exercise interventions on inflammatory biomarker levels in older adults with frailty and/or sarcopenia: a systematic review and meta-analysis

Abstract

Objective: Excessive secretion of inflammatory biomarkers exerts adverse effects on muscle strength and function, and is associated with the development and progression of sarcopenia and frailty. For the improvement of inflammatory biomarker concentrations, given the remaining limitations of current pharmacological and nutritional therapies, exercise intervention may serve as a potential non-pharmacological intervention. The purpose of this study is to systematically evaluate the effects of exercise interventions on serum inflammatory biomarker levels in older adults with frailty and/or sarcopenia by employing a meta-analysis approach.

Methods: A systematic search was conducted in PubMed, Web of Science, Cochrane Library, EMBASE, and Scopus (from database inception to October 2025) to identify randomized controlled trials (RCTs) investigating the impact of exercise interventions on serum inflammatory biomarker levels in older adults with frailty and/or sarcopenia. Data were analyzed using RevMan 5.4 and Stata 15.1. A random-effects model was employed to calculate standardized mean differences (SMD) and 95% confidence intervals (95% CI). The study protocol was registered with PROSPERO (CRD420251160555).

Results: A total of 21 studies (comprising 26 RCTs) were included, involving 1,297 participants (intervention group: 659; control group: 613) with an age range of 63.6 to 86.7 years.Meta-analysis results revealed that exercise interventions did not significantly improve serum interleukin-6 (IL-6) (SMD = -0.04, 95% CI: -0.17 to 0.09, p = 0.52, I² = 10%) or C-reactive protein (CRP) concentrations (SMD = -0.08, 95% CI: -0.25 to 0.08, p = 0.32, I² = 0%) in older adults with sarcopenia and/or frailty. However, exercise interventions exerted a significant improving effect on tumor necrosis factor-α (TNF-α) (SMD = -0.31, 95% CI: -0.44 to -0.18, p < 0.0001, I² = 37%).

Conclusion: Exercise interventions significantly improve TNF-α concentrations but do not exert a significant improving effect on IL-6 or CRP in older adults with frailty and/or sarcopenia. These findings may provide key evidence-based support for clinical non-pharmacological interventions.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251160555, identifier CRD420251160555.

Keywords: exercise; frailty; inflammatory biomarker; meta-analysis; sarcopenia.