From Athletic Performance to Functional Ageing: Shared Genetic Architecture, Redox-Inflammatory Pathways and...

Physical performance can be understood as a continuum throughout the life course, ranging from peak athletic ability in early life to the preservation of mobility and functional independence in old age. This narrative review explores whether the biological and genetic pathways involved in athletic performance might also modulate the risk of geriatric motor dysfunctions (GMDs), a conceptual umbrella proposed here for sarcopenia, dynapenia, lower-limb weakness and the motor component of physical frailty. The available evidence suggests a convergence between performance and motor decline in mechanisms such as mitochondrial function and mitophagy, anabolic-catabolic balance, oxidative stress and low-grade chronic inflammation, neuromuscular integrity, satellite cell function, mechanotransduction, myokine-mediated signalling, and the gut-muscle axis. Although classic candidate genes such as ACTN3, ACE and PPARGC1A have been useful for formulating mechanistic hypotheses, genome-wide association studies support a highly polygenic architecture for strength, lean mass, muscle weakness and frailty. These effects are strongly modulated by the exposome, particularly by physical activity, nutrition and comorbidities. Overall, the relationship appears consistent with predominantly beneficial pleiotropy, although context-dependent effects cannot be ruled out. Genetics may influence functional reserve and decline trajectories, but exercise, particularly strength and power training, along with adequate nutrition and the management of comorbidities, remain the primary strategies for preventing or delaying sarcopenia, frailty and lower-limb weakness.