Irisin ameliorates age-associated skeletal muscle atrophy in mice: potential involvement of iron overload and SIRT1/p53 pathway.

Age-associated sarcopenia is characterized by progressive loss of skeletal muscle mass and function. Irisin, a myokine, has been shown to improve sarcopenia; however, the dosage-dependence of its effects and the underlying molecular mechanisms remain unclear. To investigate the effects of irisin on age-associated sarcopenia, 22-week-old mice were used. Recombinant irisin was administered via intraperitoneal injections at doses of 0.5, 1, and 2 mg/kg, three times per week, to evaluate potential dosage-dependent effects. Skeletal muscle function was assessed using hanging time, grip strength, and muscle mass measurements. Morphological changes in muscle tissue were examined through hematoxylin and eosin staining, and fibrosis was quantified using Masson staining. Serum irisin levels were measured via enzyme-linked immunosorbent assay, and protein expression was analyzed using Western blotting. Recombinant irisin treatment significantly increased serum irisin levels in aged mice and improved functional metrics, including hanging time, maximum speed, grip strength, and muscle mass, in a dosage-dependent manner. Histological analysis revealed improvements in muscle structure and a reduction in fibrosis following irisin treatment. Molecular analyses suggested that irisin may modulate iron homeostasis and restore key oxidative stress-related proteins such as GPX4 and SLC7A11. Further exploration revealed that irisin treatment restored sirtuin 1 (SIRT1) levels, leading to deacetylation of P53 and subsequent reduction in its expression. Irisin treatment ameliorates age-associated sarcopenia in a dosage-dependent manner, potentially involving iron overload and the SIRT1/P53 pathway. These findings provide insights into the therapeutic potential of irisin for age-related skeletal muscle atrophy.