Exhaustive and/or strenuous exercise is associated with adverse shifts in aging-related molecular and physiological biomarkers, including shortened telomere length, increased 8-OHdG, upregulated IL-6, and reduced VO₂max, and these effects appear dose-dependent.
Effect size: g = 0.97, 95% CI 0.04 to 1.91, p = 0.042
IL-6 increases 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
Meta-regression suggested a model-derived inflection point around ~4000 MET-min/week, beyond which IL-6 responses appeared to increase more steeply under exhaustive/strenuous conditions
Effect size: g = -0.23, 95% CI -0.44 to -0.01, p = 0.038
VO₂max is a physiological biomarker related to cardiorespiratory fitness and aging
The reduction indicates adverse physiological adaptation under exhaustive/strenuous exercise conditions
Finding pooled across 31 included studies using a three-level random-effects model
Results
Heart rate variability (HRV) showed no significant change following exhaustive and/or strenuous exercise.
HRV was assessed as an aging-related physiological biomarker
Unlike telomere length, 8-OHdG, IL-6, and VO₂max, HRV did not reach statistical significance
This finding was part of the broader meta-analysis pooling data from 31 studies
Results
IL-6 responses to exhaustive/strenuous exercise appear dose-dependent, with a potential inflection point identified around 4000 MET-min/week.
Meta-regression indicated a linear positive relationship between exercise dose and IL-6 elevation
A model-derived inflection point of approximately ~4000 MET-min/week was identified, beyond which IL-6 responses appeared to increase more steeply
Subgroup analyses showed IL-6 increases were more pronounced in males and individuals at developing fitness level
Increases were also more pronounced following acute long-distance endurance exercise
Methods
A total of 31 studies were included in the systematic review and meta-analysis examining effects of exhaustive and/or strenuous exercise on aging-related biomarkers.
Literature search conducted across PubMed, EBSCOhost, Cochrane, and Web of Science through August 2025, updated November 2025
A three-level random-effects model was applied to pool effect sizes
Subgroup analyses and meta-regression were conducted to investigate potential moderators and dose-response relationships
Biomarkers examined included telomere length, 8-OHdG, IL-6, VO₂max, and HRV
Bao Z, Liu Y, Zhao M, Li Z, Wang H, Shi C, et al.. (2026). Effects of exhaustive and/or strenuous exercise on aging-related molecular and physiological biomarkers: a systematic review and meta-analysis.. Biogerontology. https://doi.org/10.1007/s10522-026-10411-6