Astaxanthin improves myogenicity of aged skeletal muscle progenitor cells in a sexually dimorphic manner

Age-related declines in skeletal muscle health are a major contributor to reduced mobility and development of sarcopenia in the elderly, yet effective interventions to prevent or reverse these declines are not fully optimized. Nutritional strategies to support muscle health in aging populations may be beneficial for improving muscle strength and function. In this study, we explored the effects of astaxanthin (AX), a naturally occurring antioxidant, on aged human muscle progenitor cells (hMPCs). Our findings reveal that AX enhanced proliferation and myogenic commitment of aged hMPCs, with a more pronounced effect in male hMPCs compared to female hMPCs. This dimorphism may be linked to differences in reactive oxygen species (ROS)-scavenging and effects on mitochondrial function. Other hallmarks of aging including DNA damage and cellular senescence showed differing effects of AX treatment. However, NRF2 and SIRT3 increased with AX treatment in both male and female hMPCs. This was accompanied by increased SIRT3 mitochondrial expression in males but not females, suggesting the NRF2-SIRT3 axis as a key driver of myogenicity and potential source of sexual dimorphism in response to AX. These results suggest sex-specific effects of AX in modulating aged hMPC behavior and pose a potential therapeutic strategy for combating age-related muscle decline.