Sarcopenia in older adults: pharmacological targets, trial evidence, and function-centered translational priorities

Introduction Sarcopenia in older adults is a progressive disorder of skeletal muscle characterized by loss of strength, function, and, variably, muscle quantity and quality. Despite a rapidly expanding mechanistic literature, pharmacological translation remains constrained by heterogeneous definitions, multimorbidity, short trial duration, and a recurrent mismatch between gains in lean mass and patient-centered functional outcomes. Methods We synthesized published literature on contemporary diagnostic frameworks, trial-enrichment concepts, and pharmacological and pharmacology-adjacent strategies. The evidence was organized around key biological pathways, including anabolic signaling, myostatin-activin inhibition, inflammation and redox modulation, mitochondrial and metabolic targets, and gut-muscle interactions. Results Across the evidence reviewed, changes in lean mass did not consistently translate into meaningful improvements in strength, mobility, or other patient-centered outcomes. Treatment response was phenotype-dependent and often required co-interventions, including adequate protein and energy intake, resistance training when feasible, and careful medication reconciliation. Discussion Biomarker-informed enrichment, function-centered endpoints, and pragmatic geriatric trial designs are priorities for improving translation. Pharmacological strategies should be evaluated within multimodal care to better connect biological target engagement with outcomes that matter to older adults.