Sarcopenia in Aging: Pathogenesis, Diagnosis, and Emerging Therapeutic Frontiers.

Abstract

Sarcopenia, characterized by the progressive loss of skeletal muscle mass and function, remains a formidable challenge in aging populations. This review synthesizes current knowledge on its multifactorial pathogenesis, including mitochondrial dysfunction, oxidative stress, chronic inflammation, apoptosis, and satellite cell impairment. Neuromuscular alterations such as motor unit Remodeling and neuromuscular junction degeneration further exacerbate functional decline. Diagnostic approaches, ranging from DXA, CT, MRI, and ultrasound imaging to functional assessments like handgrip strength and gait speed, exhibit variability that complicates standardization. Therapeutic strategies are equally versatile. Resistance-based exercise and targeted nutritional support remain first-line, but late-phase trials of myostatin-neutralising antibodies (e.g., LY2495655, bimagrumab) and oral selective androgen-receptor modulators (SARMs; e.g., enobosarm, GSK2881078) now show dose-dependent gains in appendicular lean mass and preliminary functional benefits, signalling that combination regimens integrating lifestyle and drug therapy are imminent. Integration of these approaches with personalized medicine paradigms and AI-driven diagnostic tools holds promise for improved outcomes. This review also outlines critical research areas including mechanistic studies, diagnostic standardization, and translational gaps between preclinical models and clinical application. Addressing these challenges requires an interdisciplinary strategy that encompasses molecular, clinical, and public health perspectives to mitigate the personal and societal impacts of sarcopenia. Future efforts must focus on harmonizing diagnostic criteria, refining therapeutic regimens, and leveraging emerging technologies to develop targeted interventions that preserve muscle function and enhance quality of life in the aging population.