Inotodiol prevents age-related muscle wasting by restoring mitochondrial function through liver X receptor beta signaling

Sarcopenia is characterized by a progressive decline in muscle mass and strength, and represents a major contributor to increased mortality in elderly population. Mitochondrial dysfunction, leading to impaired energy metabolism and elevated oxidative stress, is a key driver of muscle wasting and associated metabolic disorders. Thus, mitochondria targeting is promising strategy for combating sarcopenia. In this study, we investigated the therapeutic potential of a phytosterol inotodiol (Ino) in mitigating age-related muscle wasting and metabolic dysfunction. Ino treatment significantly improved muscle mass and function in aged mice and also prevented dexamethasone-induced muscle atrophy. Mechanistically, Ino enhanced mitochondrial function and restored muscle metabolism, as evidenced by increased mitochondrial content, elevated oxidative capacity, reduced lipid accumulation, and decreased oxidative stress. These effects are mediated by activation of the LXRβ/SIRT3/PGC-1α signaling axis, a central regulator of mitochondrial function. Collectively, our findings identify Ino as a promising therapeutic candidate that mimics key benefits of exercise.