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

被引：476

作者：

D'Antona, Giuseppe ^{[2
,3
]}

Ragni, Maurizio ^{[1
]}

Cardile, Annalisa ^{[1
]}

Tedesco, Laura ^{[1
,4
]}

Dossena, Marta ^{[1
,5
]}

Bruttini, Flavia ^{[2
,3
]}

Caliaro, Francesca ^{[2
,3
]}

Corsetti, Giovanni ^{[6
]}

Bottinelli, Roberto ^{[2
,3
]}

Carruba, Michele O. ^{[1
,4
]}

Valerio, Alessandra ^{[1
,5
]}

Nisoli, Enzo ^{[1
,4
]}

机构：

[1] Univ Milan, Sch Med, Ctr Study & Res Obes, Dept Pharmacol Chemotherapy & Med Toxicol, I-20129 Milan, Italy

[2] Univ Pavia, Human Physiol Unit, Dept Physiol, I-27100 Pavia, Italy

[3] Univ Pavia, Interuniv Inst Myol, I-27100 Pavia, Italy

[4] Ist Auxol Italiano, I-20145 Milan, Italy

[5] Univ Brescia, Pharmacol Unit, I-25123 Brescia, Italy

[6] Univ Brescia, Human Anat Unit, Dept Biomed Sci & Biotechnol, I-25123 Brescia, Italy

来源：

CELL METABOLISM | 2010年 / 12卷 / 04期

关键词：

NITRIC-OXIDE SYNTHASE; EXTENDS LIFE-SPAN; CALORIE RESTRICTION; INSULIN SENSITIVITY; ENDOTHELIAL-CELLS; MAMMALIAN TARGET; SACCHAROMYCES-CEREVISIAE; DIETARY RESTRICTION; OXYGEN-CONSUMPTION; PROTEIN-SYNTHESIS;

D O I：

10.1016/j.cmet.2010.08.016

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：362 / 372

页数：11

共 61 条

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