Sosa Patricia, Angulo Javier, Sánchez-Ferrer Alberto, Gómez-Cabrera Maria Carmen, Fernández Argentina, Rodríguez-Mañas Leocadio, El Assar Mariam
Fundación para la Investigación Biomédica del Hospital de Getafe, 28905 Getafe, Spain.
Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain.
Int J Mol Sci. 2025 Jul 15;26(14):6783. doi: 10.3390/ijms26146783.
Skeletal muscle function is determinant for maintaining functional performance and independence in older adults. Muscle is a primary target of aging and insulin resistance (IR)-two conditions associated with functional decline. Sex-related differences may influence these effects at structural and functional levels. We aimed to evaluate the individual and combined effects of aging and IR on the function and structure of extensor digitorum longus (EDL) and soleus muscles in male and female rats. Animals aged 3 and 20 months were studied, with IR induced by 8 weeks of 20% fructose in drinking water. Muscle contractility was assessed alongside histological and hormonal analyses. In males, aging impaired EDL and soleus contractile force, free testosterone levels, and muscle mass. IR decreased muscle function only in young animals. In females, aging led to muscle loss without affecting contractile strength, but the combination of aging and IR reduced muscle contraction, decreased estradiol and exacerbated muscle loss. Both sexes showed aging-related loss of EDL glycolytic fibers, altered regenerative capacity, and increased fibrosis. IR alone reduced glycolytic fibers in young animals of both sexes but increased fibrosis only in males. These results highlight sex-specific effects of aging and IR on muscle function, relevant for targeted strategies to prevent and treat age- and IR-related muscle function decline.
骨骼肌功能对于维持老年人的功能表现和独立性至关重要。肌肉是衰老和胰岛素抵抗（IR）这两种与功能衰退相关状况的主要靶点。性别相关差异可能在结构和功能层面影响这些效应。我们旨在评估衰老和IR对雄性和雌性大鼠趾长伸肌（EDL）和比目鱼肌的功能及结构的单独和联合作用。研究了3个月龄和20个月龄的动物，通过在饮水中添加20%果糖持续8周诱导IR。同时评估肌肉收缩力以及组织学和激素分析。在雄性中，衰老损害了EDL和比目鱼肌的收缩力、游离睾酮水平和肌肉质量。IR仅在年轻动物中降低肌肉功能。在雌性中，衰老导致肌肉流失但不影响收缩强度，然而衰老与IR的联合作用降低了肌肉收缩，降低了雌二醇水平并加剧了肌肉流失。两性均表现出与衰老相关的EDL糖酵解纤维丧失、再生能力改变以及纤维化增加。单独的IR减少了两性年轻动物的糖酵解纤维，但仅在雄性中增加了纤维化。这些结果突出了衰老和IR对肌肉功能的性别特异性影响，这对于预防和治疗与年龄和IR相关的肌肉功能衰退的靶向策略具有重要意义。
