Branched-chain amino acid supplementation promotes survival

Branched-chain amino acid supplementation promotes survival and supports cardiac and skeletal muscle mitochondrial biogenesis in middle-aged mice.

Authors
Giuseppe D’Antona, Maurizio Ragni, Annalisa Cardile, Laura Tedesco, Marta Dossena, Flavia Bruttini, Francesca Caliaro, Giovanni Corsetti, Roberto Bottinelli, Michele O. Carruba, Alessandra Valerio, Enzo Nisolisend emailSee Affiliations

Highlights
BCAAem supplementation increases the average life span of male mice
BCAAem activates mTOR and eNOS signaling pathways
BCAAem increases mitochondrial biogenesis and ROS defense system in middle-aged mice
BCAAem supplementation improves age-related muscle deficits
[emphasis by The Breviary]

Summary

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.

Mitochondria are so strongly implicated in aging that there’s a mitochondrial theory of aging. In the above report, the feeding of a BCAA-enhanced, essential amino acid mixture (BCAAem) caused increased mitochondrial biogenesis in mice and increased average lifespan.

The contents of the BCAAem can be found in another (freely accessible) paper by the same authors: Branched-chain amino acids, mitochondrial biogenesis, and healthspan: an evolutionary perspective. Here’s the mixture used:

In search for CR-mimetic compounds, we recently investigated the effects of a balanced amino acid mixture with a high content of branched-chain and other essential amino acids (BCAA-enriched mixture, BCAAem; % composition: leucine 31.3, lysine 16.2, isoleucine 15.6, valine 15.6, threonine 8.8, cysteine 3.8, histidine 3.8, phenylalanine 2.5, methionine 1.3, tyrosine 0.7, tryptophan 0.5) which had been found to improve age-related disorders in animals and humans (see below). We demonstrated that BCAAem oral supplementation (1.5 mg/g body weight/day beginning at 9 months) increases the average, but not maximal lifespan of male mice [12]. Along with increased survival, BCAAem-supplemented middle-aged (16 months) mice showed up-regulated PGC-1α and SIRT1 expression and enhanced mitochondrialbiogenesis and function in cardiac and skeletal muscles but not in adipose tissue or liver. Further, the BCAAem preserved muscle fiber size and improved physical endurance and motor coordination in middle-aged mice [12].

Whey protein is about 50% essential amino acids, with about half of those being BCAAs, so the closest substitute for the mixture used might be whey protein. Using this convenient human-equivalent dose chart, the dose of the BCAAem for humans would be .12 g/kg body weight/day, or for a 75 kilogram man, about 9 grams a day. If whey is about 50% essential amino acids, then double that to 18 grams, about the same as one average whey protein shake. Additional leucine should probably be taken as well, say another couple grams or so. (Leucine is available here, and these folks also have a good, cold-processed, non-denatured whey.)

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2 comments
Anonymous says August 28, 2012

Branched-chain amino-acids, and dairy products in general, have been linked to prostate cancer:

http://www.nutritionandmetabolism.com/content/9/1/74

Anon.

Reply
BrokenSymmetry says September 9, 2012

BCAAs are potent inducers of mTOR signaling (specifically mTOR Complex I) which may have beneficial short term effects. However long-term, it may be more beneficial to depress mTORC1 signaling. Rapamycin, the classical mTORC1 inhibitor, is the only compound shown to increase life- and health-span in mammals (lab mice).

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