Phytochemical-Based Therapeutic Strategies for Sarcopenia: From Molecular Mechanisms to Clinical Translation

Sarcopenia is a progressive, age-related musculoskeletal disorder characterized by the loss of skeletal muscle mass, strength, and physical performance, which contributes to frailty, disability, and mortality in older adults. Although resistance exercise and optimized protein intake remain first-line interventions, effective pharmacological therapies are limited, highlighting the need for novel adjunctive strategies. Increasing interest has focused on phytochemicals, plant-derived bioactive compounds with antioxidant, anti-inflammatory, and metabolic regulatory properties that may target multiple mechanisms underlying muscle aging. This review summarizes the molecular and translational potential of phytochemicals in sarcopenia management. Experimental and emerging clinical evidence indicates that flavonoids, polyphenols, alkaloids, and terpenoids modulate key pathways involved in sarcopenia pathogenesis, including PI3K/Akt/mTOR-mediated anabolic signaling, AMPK-SIRT3-PGC-1α-dependent mitochondrial biogenesis, NF-κB-driven inflammation, oxidative stress responses, autophagy, and satellite cell function. Through these pleiotropic effects, phytochemicals may attenuate the anabolic resistance, mitochondrial dysfunction, chronic inflammation, and impaired muscle regeneration associated with aging. Despite promising mechanistic evidence, clinical translation remains limited by poor bioavailability, variability in formulation and dosing, a lack of long-term randomized trials, and inconsistent functional outcome measures. Current evidence suggests that phytochemicals are most effective when integrated with resistance exercise and nutritional support rather than used as stand-alone therapies. Overall, phytochemicals represent promising complementary candidates for sarcopenia prevention and management. Future studies should prioritize standardized formulations, biomarker-guided approaches, and rigorously designed clinical trials focused on clinically meaningful functional outcomes to establish their efficacy, safety, and translational relevance in aging populations.