This study aimed to investigate the impact of sprint interval training (SIT) on both the acute and 3-week modulations of cell-free DNA (cfDNA), as well as its association with neuromuscular fatigue and physical performance in healthy young and old men. Ten young (20-25year old) and nine elderly (63-72year old) healthy men performed nine SIT sessions consisting of 4-to-6-all-out cycling repetitions of 30s interspaced with 4-min rest intervals. We compared the maximal voluntary contractions torque, central activation ratio, low-frequency fatigue (LFF), and cfDNA concentrations between the groups before, immediately after, 1h after, and 24h after the first and ninth SIT sessions. The plasma cfDNA levels were increased post-exercise (from 1.4 ± 0.258 to 1.91 ± 0.278ng/ml (P < 0.01) on a log10 scale), without significant differences between the groups. However, older individuals showed a slight decrease in the baseline cfDNA values, from 1.39 ± 0.176 to 1.29 ± 0.085ng/ml on a log10 scale, after 3weeks (P = 0.043). Importantly, the elevation of the post-exercise cfDNA values was correlated with an increase in LFF in both groups. Three weeks of SIT induced an improvement in the recovery of LFF (main session effect, P = 0.0029); however, only the young group showed an increase in aerobic capacity (VO2max) (from 40.8 ± 6.74 to 43.0 ± 5.80ml/kg/min, P = 0.0039). Three weeks of SIT diminished the baseline cfDNA values in the old group, together with an improvement in the recovery of LFF. However, VO2max was increased only in the young group.
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