Strengthening muscle for healthy ageing: innovative treatments for sarcopenia

Millions of people worldwide suffer from sarcopenia, a clinically recognized syndrome that is defined as the age-related loss of skeletal muscle mass and strength. Sarcopenia reduces mobility, leads to falls and fractures, and increases the risk of death, posing an ever-increasing health-care and economic burden to society. There are currently no approved therapies for the syndrome, partly owing to its multifactorial aetiology, highlighting the need for therapies with pleiotropic beneficial effects on muscle function. Increased understanding of the cellular, metabolic and molecular mechanisms that drive muscle wasting with ageing is informing pharmacological interventions to increase muscle strength by promoting mitochondrial function (NAD⁺-related molecules, urolithin A), restoring impaired autophagy (mTORC1 inhibitors), promoting anabolic signalling (myostatin inhibitors), acting as selective androgen receptor modulators, maintaining vascularization (VEGF, apelin), reducing inflammageing (inhibitors of cytokine signalling), and restoring innervation, anabolism and regeneration (inhibitors of the gerozyme 15-PGDH). The recent surge in clinical trials combining weight loss-inducing GLP1RA therapies with drugs that preserve muscle tissue suggests that treatments that promote both healthspan and lifespan, or 'healthy ageing', are on the horizon.