Performance and metabolism are reported to relate more closely to the ventilatory threshold (Tvent) than to peak oxygen uptake (VO 2 peak). Normalizing exercise to a percentage of VO 2 peak at Tvent may help better interpret DNA damage and facilitate comparisons between sexes. Accordingly, the purpose of this study was to examine the effects of a 2-hour moderate-intensity endurance exercise on systemic DNA damage and repair, focusing on sex-based differences in moderately trained men and women with equivalent anaerobic thresholds. It was hypothesized that higher fitness levels would enhance DNA repair, reducing DNA damage, with similar sex-specific responses. Moderately active male and female volunteers were recruited, with 22 of them (12 men M: age: 20.0±1.3 years, 10 women W: age: 20.9±0.3 years) exhibiting comparable anaerobic threshold levels, normalized to a percentage of VO 2 peak at ventilatory threshold (M: 57.7±9.7, F: 52.6±11.7), subsequently selected for the study. All volunteers carried out an incremental exercise test to volitional exhaustion to evaluate cardiorespiratory indices (ventilatory threshold VO 2 at Tvent, respiratory compensation point VO 2 at RCP, and VO 2 peak; all expressed in ml/kg fat-free mass/min) on an electromagnetically braked cycle ergometer. In all 22 individuals, 2-hour urinary samples were taken at three time points: before (-2–0 h), immediately after (0–2 h), and 24–26 h after 2 hours of submaximal cycling exercise at 60%VO 2 peak, followed by the quantification of urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG, a potential marker of whole-body DNA oxidation DNA damage/repair balance) using high-performance liquid chromatography with electrochemical detection. The female participants performed the submaximal exercise protocol during the early follicular phase of their menstrual cycle (5 to 9 days following the onset of menstruation) to control for hormonal influences on exercise-induced metabolic responses. Percent changes in urinary 8-OHdG were calculated using values before (-2–0 h) and 24–26 h after exercise. Pearson’s correlation coefficients were calculated separately for men and women to examine the relationships of the percent change in urinary 8-OHdG concentration (pre vs 24–26 h post-exercise) with each of VO 2 at Tvent, VO 2 at RCP, and VO 2 peak. Fisher’s Z-transformation was applied to normalize the correlation coefficients. A Z-test was then used to compare the Z-scores between sexes. Correlation analysis demonstrated no significant associations of the percent change in urinary 8-OHdG concentration with VO 2 at Tvent (M: r=0.292, p=0.357; W: r=-0.452, p=0.190), VO 2 at RCP (M: r=0.301, p=0.342; W: r=0.102, p=0.779), or VO 2 peak (M: r=0.429, p=0.164; W: r=-0.001, p=0.997). Additionally, Fisher’s Z-transformation followed by a Z-test also revealed no significant sex-specific differences in these variables between men and women with matched anaerobic thresholds. The present study indicates that moderately prolonged exercise does not induce detectable DNA damage in moderately active men and women, likely due to enhanced antioxidant defense mechanisms. Moreover, men and women with similar anaerobic threshold levels appear to exhibit similar whole-body DNA oxidation responses, although this marker was not significantly associated with cardiorespiratory indices. This work was supported by Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (Grant No. 23500867 and 25K14756). This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Nobuo Yasuda (2026) studied this question.