Branched-Chain Amino Acid Supplementation Promotes Survival and Supports Cardiac and Skeletal Muscle Mitochondrial Biogenesis in Middle-Aged Mice

Abstract

Recent evidence points to a strong relationship between increased mitochondrial biogenesis and increased survival in eukaryotes. Branched-chain amino acids (BCAAs) have been shown to extend chronological life span in yeast. However, the role of these amino acids in mitochondrial biogenesis and longevity in mammals is unknown. Here, we show that a BCAA-enriched mixture (BCAAem) increased the average life span of mice. BCAAem supplementation increased mitochondrial biogenesis and sirtuin 1 expression in primary cardiac and skeletal myocytes and in cardiac and skeletal muscle, but not in adipose tissue and liver of middle-aged mice, and this was accompanied by enhanced physical endurance. Moreover, the reactive oxygen species (ROS) defense system genes were upregulated, and ROS production was reduced by BCAAem supplementation. All of the BCAAem-mediated effects were strongly attenuated in endothelial nitric oxide synthase null mutant mice. These data reveal an important antiaging role of BCAAs mediated by mitochondrial biogenesis in mammals.

Protect and Counter-attack: Nutritional Supplementation with Essential Amino acid Ratios Reduces Doxorubicin–induced Cardiotoxicity in vivo and promote Cancer Cell Death in vitro

“…p<0.05) (Figure 1a The in vivo findings were partially surprising because previous studies had shown that EAA nutritional supplementation stimulates mitochondrial biogenesis and endogenous defences against ROS. The consequences were: reduced cell damage, improved cellular energy production and preserved muscular structure, which finally increased life span of aged animals [1].As expected, the in vitro experiments confirmed the Doxo action on cancer cells, causing about 60% of cell death vs untreated (control) cell after 24h. On the contrary and surprisingly, EAA administration with or without Doxo, increased cancer cell mortality (Figure 1b).…”

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CommentaryHuman and experimental data show that nutritional supplementation with a specific mixture of essential amino (EAA) improves both mitochondrial function and biogenesis and reduces either ROS formation or apoptotic drive in myocytes [1][2]. Supplementation with EAA is also effective in humans when tested in patients with cardiac dysfunction [3].

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Nutrition, Nitrogen Requirements, Exercise and Chemotherapy-Induced Toxicity in Cancer Patients. A puzzle of Contrasting Truths?

“…This was accompanied by enhanced physical endurance. Moreover, the ROS defense genes were upregulated, and ROS production was reduced [99]. EAA supplementation was also effective in reducing damage caused by alcohol in the liver and by rosuvastatin in the kidney [146,147].…”

“…Indeed in these cells an increased amount of cleaved caspase 3, after treatment with AAs, was detected. In our experimental setup, the amino acids (for the detailed mixture composition see ref [99]) are provided exogenously in elevated quantities. Under these conditions the mTORC1 is activated as previously observed [100,101].…”

Diet mediates the relationship between longevity and reproduction in mammals

“…Focal studies of several animals have shown that, by holding total caloric content constant and varying the ratio of carbohydrates and protein or key amino acids in food, individuals fed high-protein diets have much shorter lifespans than those fed diets with less protein and more carbohydrates (Miller et al 2005;Lee et al 2008;Maklakov et al 2008;Fanson et al 2009;Simpson and Raubenheimer 2009). Changes in the concentrations of specific amino acids in the diet, especially branched-chain amino acids, could also affect longevity (Alvers et al 2009;D'Antona et al 2010). Another potential explanation is that, while the food that carnivores consume better allows them to avoid conflicts between reproduction and longevity, the overall availability of this food may be lower for carnivores and, hence, limit their realized reproduction and longevity.…”