Reframing sarcopenia as a disease of the ageing motor system.

Abstract

Sarcopenia is a major driver of disability, frailty, and loss of independence in ageing populations. Current consensus definitions have shifted from low muscle mass to low muscle strength and impaired physical performance as the defining clinical features. The underlying disease model, however, has remained predominantly muscle-centric, a framing that has generated important advances in muscle biology but has also guided decades of muscle-focused research in which drugs that increase muscle mass have produced inconsistent functional benefits. Muscle mass and intrinsic muscle quality account for an important but incomplete proportion of age-related declines in strength and mobility. Ageing disrupts the entire motor system, from supraspinal centres, spinal circuitry, and peripheral nerves to neuromuscular junctions and muscle, reducing neural drive, coordination, and force generation. We propose reframing sarcopenia as a disease of the ageing motor system. Although existing strength-based and performance-based criteria capture the clinical syndrome, there is scope for improvement. The disease model and diagnostic framework should evolve to reflect the distributed biology of sarcopenia, guiding integrated assessment, mechanistic stratification, and therapies that target both neural and muscular mechanisms. Without this shift, meaningful therapeutic progress will remain challenging.