From Liver to Muscle: Crosstalk Mechanisms and Interventions in Sarcopenia

Aging is a complex and multifactorial process, characterized by a gradual decline of multiple organ systems. Increasing evidence suggests that organ crosstalk plays a crucial role in aging. It is particularly important in the development of age-related diseases like sarcopenia. The liver significantly impacts skeletal muscle health by influencing metabolic health, inflammatory signals, and the secretion of hepatokines. Chronic liver diseases, including non-alcoholic fatty liver disease (NAFLD), cirrhosis, and hepatocellular carcinoma (HCC), exacerbate sarcopenia by disruptiong the liver-muscle interactions. Recent studies have demonstrated that liver-derived metabolites, including ketone bodies, can modulate the skeletal muscle function. Notably, beta-hydroxybutyrate (BHB), a key liver-derived metabolite, has been shown to mediate post-translational modifications (PTMs) in muscle, reversing sarcopenia through beta-hydroxybutyrylation. This review explores the relationship between liver aging, chronic liver diseases, and sarcopenia. It focuses on mediators of liver-muscle crosstalk, including metabolic integration, hepatokines, and miRNAs in extracellular vesicles (EVs). We highlight the impact of liver-derived metabolites on skeletal muscle post-translational modifications, particularly the role of BHB in muscle rejuvenation and sarcopenia reversal. Understanding these mechanisms provides new insights into potential therapeutic strategies for mitigating sarcopenia via living aging intervention.