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

ABSTRACT 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.