Aging skeletal muscle displays an altered iron status that may promote oxidative stress and sarcopenia. A low iron (LI) containing diet could reduce muscle iron status and attenuate age-related muscle atrophy. Supplemental branched-chain amino acids (BCAA) may also alleviate sarcopenia by promoting muscle protein synthesis and iron status improvement. This study examined individual and combined effects of LI and BCAA diets on anabolic signaling and iron status in skeletal muscle of aging rats. Twenty-nine-month-old male F344BN rats consumed the following control-base diets: Control + regular iron (35 mg iron/kg) (CR; n = 11); Control + LI (~6 mg iron/kg) (CL; n = 11); 2×BCAA + regular iron (BR; n = 10); and 2×BCAA + LI (BL; n = 12) for 12 weeks. Although LI and/or 2×BCAA did not affect plantaris muscle mass, 2×BCAA groups showed lower muscle iron content than did CR and CL groups (P < 0.05). p70S6 kinase phosphorylation was greater in 2×BCAA and LI animals compared to CR animals (P < 0.05). Interactions between IRON and BCAA were observed for proteins indicative of mitochondrial biogenesis (PGC1-α) and oxidative capacity (COX-2 and citrate synthase) (P < 0.05) wherein the combined diet (BL) negated potential benefits of individual diets. Antioxidant capacity, superoxide dismutase (SOD) activity, and oxidative injury (3-nitrotyrosine (3-NT), protein carbonyls, and 4-hydroxynonenal (4-HNE)) were similar between groups. In conclusion, 12 weeks of LI and 2×BCAA diets showed significant impacts on increasing anabolic signaling as well as ameliorating iron status, however these interventions did not affect muscle mass.
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