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. � 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.
D'Antona, Giuseppe; Ragni, Maurizio; Cardile, Annalisa; Tedesco, Laura; Dossena, Marta; Bruttini, Flavia; Caliaro, Francesca; Corsetti, Giovanni; Bottinelli, Roberto; Carruba, Michele O.; Valerio, Alessandra; Nisoli, Enzo
The full text is here
Cell metabolism
doi:10.1016/j.cmet.2010.08.016 (volume 12 issue 4
pp.362 - 372)
(MDN)
|