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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.
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; Sánchez-Ferrer, Alberto 3 ; Gómez-Cabrera, Maria Carmen 4
; Fernández Argentina 5 ; Rodríguez-Mañas Leocadio 6
; El Assar Mariam 1
1 Fundación para la Investigación Biomédica del Hospital de Getafe, 28905 Getafe, [email protected] (A.S.-F.), Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain; [email protected] (J.A.); [email protected] (M.C.G.-C.), Instituto de Investigación IdiPaz, 28029 Madrid, Spain
2 Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain; [email protected] (J.A.); [email protected] (M.C.G.-C.), Servicio de Histología-Investigación, Unidad de Investigación Traslacional en Cardiología–IRYCIS/UFV, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain; [email protected]
3 Fundación para la Investigación Biomédica del Hospital de Getafe, 28905 Getafe, [email protected] (A.S.-F.), Instituto de Investigación IdiPaz, 28029 Madrid, Spain
4 Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain; [email protected] (J.A.); [email protected] (M.C.G.-C.), Freshage Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, Fundación Investigación Hospital Clínico Universitario/INCLIVA, 46010 Valencia, Spain
5 Servicio de Histología-Investigación, Unidad de Investigación Traslacional en Cardiología–IRYCIS/UFV, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain; [email protected]
6 Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain; [email protected] (J.A.); [email protected] (M.C.G.-C.), Instituto de Investigación IdiPaz, 28029 Madrid, Spain, Servicio de Geriatría, Hospital Universitario de Getafe, 28905 Getafe, Spain