Physical Performance & Age-Associated Decline: The Nature Communications Data

In 2021, Reynolds et al. reported in Nature Communications (PMID: 33473133) that endogenous MOTS-c is an exercise-induced mitokine. Human sedentary young males performing exhaustive cycle ergometer trials showed robust circulating MOTS-c spikes that localized to skeletal muscle beds.

Furthermore, in sedentary aged mice, intermittent MOTS-c administration significantly restored physical performance, running distance, and grip strength to levels comparable to younger counterparts. Mechanistically, it remodeled glucose uptake cascades without elevating fasting hypoglycemia risk. For researchers studying longevity and metabolic elasticity, these trial findings represent the most rigorous translational benchmark available in peer-reviewed literature.