Abstract
This review systematically maps the causal and mechanistic connections between selenium status and sarcopenia, a debilitating condition characterized by age-related loss of muscle mass, strength, and function. Current evidence reveals a strong and consistent association across studies. Epidemiological data demonstrate that lower levels of various selenium biomarkers, including serum/plasma selenium, whole blood selenium, the selenium transport protein SELENOP, and dietary selenium intake, are significantly associated with poorer muscle outcomes, such as decreased grip strength, reduced muscle mass, and a higher prevalence of sarcopenia, following a dose-response pattern. A clinical study further confirms significantly lower serum selenium levels and glutathione peroxidase activity in patients with sarcopenia, linking elevated muscle oxidative stress to depleted selenium status. In animal models, sarcopenia is associated with reduced muscle selenium content, whereas selenium supplementation effectively prevents this decline and attenuates muscle atrophy and weakness. The underlying protective mechanisms are primarily mediated through specific selenoproteins. GPX4 preserves mitochondrial function and muscle mass by detoxifying lipid peroxides, suppressing inflammation, and preventing ferroptosis. SELENOP, secreted by macrophages, resolves inflammation and supports muscle stem cell-mediated regeneration. SELENOW, highly expressed in skeletal muscle, maintains protein homeostasis by regulating the RAC1-mTOR pathway to counteract atrophy. Additionally, SELENOT and SELENON are critical for maintaining intracellular calcium homeostasis, which is essential for normal muscle contraction. In conclusion, selenium deficiency constitutes a significant risk factor for sarcopenia. Ensuring adequate selenium intake supports a network of selenoproteins that combat oxidative stress, regulate inflammation, promote muscle regeneration, and maintain protein and calcium homeostasis, underscoring its importance in nutritional strategies for preserving muscle health in aging populations.