The Emerging Role of α-Klotho as a Therapeutic Target for Sarcopenia: Underlying Mechanisms and Clinical Prospects

Sarcopenia is a syndrome characterized by progressive decline in skeletal muscle mass, strength, and physical performance. It has become a common pathological manifestation of aging, physical inactivity, and multiple chronic diseases. The α-Klotho protein, a well-established anti-aging factor, exists in both membrane-bound and soluble forms. Soluble α-Klotho (s-α-Klotho) circulates systemically and performs a wide range of physiological functions. Studies indicate that α-Klotho is closely associated with multiple age-related disorders, including diabetes, osteoporosis, chronic kidney disease, and neurodegenerative diseases such as Alzheimer's and Parkinson's. Notably, recent studies have revealed reduced expression of α-Klotho in sarcopenia, implicating it in the disease pathogenesis through the regulation of multiple signaling pathways. Given its anti-aging properties, α-Klotho has emerged as a promising therapeutic target for sarcopenia. This review summarizes current evidence supporting the role of α-Klotho in sarcopenia, with a focus on its mechanisms of action in determining skeletal muscle cell fate. Furthermore, it evaluates the potential of various α-Klotho-targeted interventions to ameliorate sarcopenia and discusses challenges and future directions in this evolving field.