Male offspring of endurance-trained fathers had higher VO2max

Peter Attia shared this recently in his Research Worth Sharing.  And I thought it would be worth sharing here also

Paternal exercise confers endurance capacity to offspring through sperm microRNAs

Why we are interested: We’ve spent a lot of time discussing the benefits of cardiorespiratory fitness for individual longevity. This animal study extends that idea by suggesting that endurance training in fathers can confer fitness advantages to male offspring—even when those offspring never exercise themselves.1 Central to this work is PGC-1α, a transcriptional coactivator widely regarded as the “master regulator” of mitochondrial biogenesis and oxidative metabolism, and a molecule long linked to endurance adaptations.

What they showed: The authors showed that male offspring of endurance-trained fathers had higher VO2max, lower lactate accumulation during exercise, and could achieve a higher maximal running speed before exhaustion compared to the offspring of sedentary fathers. The benefit seen in the offspring occurred without changes in traditional cardiac remodeling measures such as heart size or the amount of blood leaving the heart. Instead, adaptations were muscle-specific: offspring displayed a shift toward more oxidative fibers and away from glycolytic fibers in the calf muscle. 

They then showed that many of these same benefits could be passed on by sedentary fathers who had exercise-like physiology because of a transgene that overexpressed PGC-1α in muscle. The sedentary offspring of such mice that did not inherit the transgene still benefitted from their fathers’ physiology, showing greater endurance, cardiorespiratory fitness, and other parameters similar to exercise-trained animals, suggesting that PGC-1α might play a key role in the father-to-pup benefits of exercise.

The authors traced this intergenerational signal to small RNAs carried in sperm. Transferring sperm small RNAs from trained fathers into wild-type embryos was sufficient to reproduce the endurance phenotype in offspring, indicating a causal role for these molecules. Endurance exercise and muscle-specific PGC-1α activation both remodeled sperm microRNA profiles, but these changes did not persist beyond one generation. Finally, several of the exercise-responsive sperm microRNAs identified in mice were also altered in sperm from endurance-trained humans compared with untrained individuals, strengthening the case that the epigenetic mechanisms described here extend beyond a single species.

Together, these findings offer yet another reason to prioritize endurance training—not only for personal health and longevity, but for its potential to influence the metabolic fitness of the next generation.

doi: 10.1016/j.cmet.2025.09.003