Comparative efficacy of aerobic training, resistance training, combined training, and multicomponent exercise on interleukin-6, C-reactive protein, and tumor necrosis factor-α levels in older adults (≥60 years): a systematic review and network meta-analysis

Objective To compare and rank the efficacy of four exercise training modalities—aerobic training (AT), resistance training (RT), combined training (AT+RT), and multicomponent exercise (MCEx)—on serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) in older adults, and to examine whether the optimal modality differs by participants’ health status (healthy vs. chronic disease). Methods Strictly following the PRISMA guidelines, two researchers independently performed literature screening, methodological quality assessment, and data extraction in accordance with pre-established inclusion and exclusion criteria. A three-level meta-analysis was used to address the correlation of effect sizes in multi-arm trials; a frequentist random-effects network meta-analysis was conducted to compare and rank the intervention effects of aerobic training (AT), resistance training (RT), combined training (AT+RT), and multicomponent training (MCEx). The Cochrane Risk of Bias tool was used to assess the risk of bias of the included studies, and the GRADE framework was used to evaluate the certainty of evidence. The main effect size was the standardized mean difference (SMD) and its 95% confidence interval (95%CI), and the total I² statistic (I²_total) was used to quantify heterogeneity. In addition, double subgroup analysis was carried out based on different exercise intervention methods and different physical states of the elderly. Results A total of 82 studies were included, involving 6493 participants, of which 3125 were in the control group and 3368 were in the experimental group, with a mean age of 71.04 years. Multilevel meta-analysis showed that exercise intervention could significantly reduce the levels of IL-6 (SMD = -0.31), CRP (SMD = -0.44), and TNF-α (SMD = -0.40) in the elderly. Subgroup analysis showed that AT+RT had the best improvement effect on IL-6, RT on CRP, and AT on TNF-α. Double subgroup analysis suggested that for the elderly with chronic diseases, RT and AT+RT could effectively improve their IL-6 and CRP levels; for healthy elderly, AT was an effective method to reduce their TNF-α levels. Network meta-analysis showed that AT ranked the best in reducing IL-6 (SUCRA = 84.6%) and TNF-α (SUCRA = 97.5%), while RT ranked the best in reducing CRP (SUCRA = 89.1%). Most of the included studies had unclear or high risk of bias, and the certainty of evidence for all three outcome indicators was very low based on GRADE assessment. Conclusion Based on very low GRADE evidence, exercise interventions may reduce IL-6, CRP, and TNF-α in older adults, with aerobic training showing the highest probability of benefit for IL-6 and TNF-α, and resistance training for CRP. However, due to high risk of bias, heterogeneity, and publication bias, these findings are exploratory and require confirmation in high-quality trials. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420261320198 , identifier CRD420261320198.