Effects of long-term exposures to low iron and branched-chain amino acid containing diets on aging skeletal muscle of Fisher 344 × Brown Norway rats

Abstract

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.

The contradictory role of branched-chain amino acids in lifespan and insulin resistance

“…On the other hand, supplementation with BCAAs can also improve aging by promoting muscle protein synthesis and iron content ( 23 ), and BCAA supplementation significantly inhibits the decrease in serum albumin in elderly patients compared with that in young patients ( 24 ). In addition, BCAA supplementation can promote wound healing, reduce the occurrence of kidney and liver diseases with age ( 25 ), and reduce inflammatory markers in patients with chronic heart failure ( 26 ).…”

Productive and physiological implications of top-dress addition of branched-chain amino acids and arginine on lactating sows and offspring

“…In addition, an increase in both BCAAs and Arg in the diet could have a synergetic effect by means of activating the target of rapamycin complex (mTOR) cell signalling [5]; in fact, in rats, BCAAs can inhibit the catabolism of Arg in the mammary tissue and increase its availability [22], therefore, the increased availability of Arg would increase the synthesis of nitric oxide which acts as a major vasodilator increasing the blood flow and, in turn, the uptake of nutrients [5,17]. However, to the authors' knowledge, no study has investigated this potential synergic effect between BCAAs and Arg.…”

Branched-chain amino acids are linked with iron metabolism

“…Certain studies suggested a possible link between BCAAs, mTORC1 and hematological parameters (9)(10)(11). Significant increases in hemoglobin (Hb), serum iron, red blood cell count and hematocrit were observed in a small cohort of 23 athletes after a 90-day administration of a BCAAmixture (9).…”