Association of Cardiorespiratory Fitness with DNA Damage Repair, Telomere Length, and Mitochondrial DNA Copy Number in Adolescent Male and Female Athletes

As adolescent athletes increasingly engage in long-term training to improve their performance levels, they are also at increased risk of overtraining. In this regard, given that non-invasive biomarkers such as saliva and urine samples can be used to rapidly provide information to athletes and coaches, they will provide clues for determining optimal training thresholds. Accordingly, the aim of this study was to investigate the association of cardiorespiratory fitness with DNA damage repair, telomere length, and mitochondrial copy number in adolescent male and female athletes, using non-invasive biomarkers. It was hypothesized that elevated fitness levels could lead to an increased mitochondrial DNA copy number and also accelerate DNA damage repair, resulting in less DNA damage, and that telomere length would be maintained as no significant changes would be observed. Twenty-five adolescent male (n=14, age: 15.2±1.6 years) and female athletes (n=11, age: 15.1±0.8 years) participated in this study. They had similar aerobic fitness levels [M: 78.6±9.8, F: 72.3±5.7 peak oxygen uptake (VO 2 peak) ml/kg fat-free mass/min)], had been training regularly for at least six months, and competed at the national level. They trained at least five to six times per week for two to three hours per session. Saliva samples were collected using a saliva collection kit before evaluating cardiorespiratory fitness. Saliva was used to extract DNA, which was subsequently quantified for telomere length and mitochondrial DNA copy number using real-time PCR. Each participant's VO 2 peak was measured on a bicycle ergometer using an incremental load method to determine aerobic capacity. Two-hour urine samples were taken before acute moderate-intensity exercise (1 hour at 65% VO 2 peak) and on day 2 after exercise to assess DNA damage repair [percent change in urinary 8-hydroxy-2'-deoxyguanosine levels: urinary 8-OHdG (ng/mg creatinine)] with high performance liquid chromatography. Correlation analysis revealed significant associations of cardiorespiratory fitness with mitochondrial DNA copy number (r=0.414, p<0.05) and DNA damage repair levels (r=0.448, p<0.05). In contrast, there were no significant relationships between cardiorespiratory fitness and telomere length (r=0.320, p=0.118). Furthermore, no significant sex-specific differences were observed in the above dependent variables for male and female athletes with similar aerobic capacity. The findings of this study indicate that an increase in mitochondrial DNA copy number is associated with an augmentation of mitochondrial content in slow-twitch muscle fibers, which in turn is linked to enhanced aerobic capacity. Moreover, the results of the present study imply that telomere length is maintained as cardiorespiratory fitness improves. In addition, the results suggest a close link between aerobic capacity and DNA damage repair. This study was supported partly by funds from the Grant-in-Aid for Scientific Research (C) (Grant No.19K11617 and 22K11671). This abstract was presented at the American Physiology Summit 2025 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.