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Effects of exhaustive and/or strenuous exercise on aging-related molecular and physiological biomarkers: a systematic
Zihan Bao1, Yunyang Liu1,2, Mengqi Zhao1
1School of Physical Education, Huaibei Normal University, Huaibei, China.
Abstract:
Exercise, a well-recognized non-pharmacological anti-aging strategy, is key for human health. Growing evidence points to exhaustive or strenuous exercise, especially when recovery is inadequate, may trigger oxidative damage and accelerate aging. This study aims to systematically the effects of exhaustive and/or strenuous exercise on aging-related molecular and physiological biomarkers using a systematic review and meta-analysis. A systematic literature search was conducted across PubMed, EBSCOhost, Cochrane, and Web of Science through August 2025 and was updated in November 2025. A three-level random-effects model was applied to pool effect sizes, and subgroup analyses along with meta-regression were conducted to investigate potential moderators and dose-response relationships. A total of 31 studies were included. Exhaustive and/or strenuous exercise significantly shortened telomere length (g = - 0.44, 95% CI - 0.83 to - 0.03, p = 0.037), increased 8-OHdG levels (g = 0.97, 95% CI 0.03 to 0.80, p = 0.036), upregulated IL-6 (g = 0.97, 95% CI 0.04 to 1.91, p = 0.042), and reduced VO₂max (g = - 0.23, 95% CI - 0.44 to - 0.01, p = 0.038), while HRV showed no significant change. Increases in IL-6 were more pronounced in males, individuals with developing level, and following acute long-distance endurance exercise. IL-6 exhibited a linear positive relationship with exercise dose, with the meta-regression suggesting a model-derived inflection point around ~ 4000 MET-min/week, beyond which IL-6 responses appeared to increase more steeply under exhaustive/strenuous conditions. Exhaustive and/or strenuous exercise is associated with adverse shifts in aging-related molecular and physiological biomarkers, and these effects appear dose-dependent. Future studies ought to focus on the identification of dose thresholds and clarification of regulatory factors, thereby facilitating the development of more precise, evidence-informed exercise dose frameworks in the context of aging.
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