Bridging the Translational Gap in Sarcopenia: Integrating Novel Biologics with Established Lifestyle Interventions

Abstract

Background: Sarcopenia is a progressive, age-related loss of skeletal muscle mass and function that drives frailty, disability, and mortality in older adults. Despite an expanding pipeline of pharmacological, biologic, cell-based, and genetic candidates, clinical translation has been inconsistent, and lifestyle intervention remains the only strategy with robust, reproducible functional benefits. Objective: This narrative review synthesizes evidence across pharmacological and hormonal therapies, myokine-, adipokine-, and myostatin-based strategies, cell-based and mitochondrial-targeted approaches, and genetic and epigenetic interventions for sarcopenia and evaluates why translation from mechanistic promise to functional clinical benefit remains limited. Methods: A structured literature search was conducted in PubMed, Scopus, and Web of Science. Eligible publications included peer-reviewed original research, randomized controlled trials, phase I-III clinical studies, mechanistic preclinical investigations, and prior reviews addressing sarcopenia or related mechanisms of muscle aging, as detailed in the Methodological Approach section below. Key findings: Across nearly every therapeutic class reviewed, biochemical or biomarker-level improvement does not reliably predict functional benefit, a pattern recurring in hormonal-, myokine-, mitochondrial-, and gene-based candidates alike. Exercise, supported by nutritional optimization, remains the only intervention that reliably improves both muscle mass and functional outcomes, likely because it engages multiple biological pathways simultaneously rather than a single molecular target. Conclusion: Future progress is likely to depend less on identifying a single transformative molecule than on reframing functional end points as the primary standard for evaluating candidate therapies and on developing adjunct interventions designed to complement, rather than replace, multimodal exercise and nutritional care.