Branched-chain amino acid supplementation promotes survival and supports cardiac and skeletal muscle mitochondrial biogenesis in middle-aged mice.
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.
D'Antona
Giuseppe
G
Department of Physiology, Human Physiology Unit, Pavia University, Pavia 27100, Italy; Interuniversity Institute of Myology, Pavia University, Pavia 27100, Italy.
Ragni
Maurizio
M
Center for Study and Research on Obesity, Department of Pharmacology, Chemotherapy and Medical Toxicology, School of Medicine, Milan University, Milan 20129, Italy.
Cardile
Annalisa
A
Center for Study and Research on Obesity, Department of Pharmacology, Chemotherapy and Medical Toxicology, School of Medicine, Milan University, Milan 20129, Italy.
Tedesco
Laura
L
Center for Study and Research on Obesity, Department of Pharmacology, Chemotherapy and Medical Toxicology, School of Medicine, Milan University, Milan 20129, Italy; Istituto Auxologico Italiano, Milan 20145, Italy.
Dossena
Marta
M
Center for Study and Research on Obesity, Department of Pharmacology, Chemotherapy and Medical Toxicology, School of Medicine, Milan University, Milan 20129, Italy; Pharmacology Unit, Department of Biomedical Sciences and Biotechnologies, Brescia University, Brescia 25123, Italy.
Bruttini
Flavia
F
Department of Physiology, Human Physiology Unit, Pavia University, Pavia 27100, Italy; Interuniversity Institute of Myology, Pavia University, Pavia 27100, Italy.
Caliaro
Francesca
F
Department of Physiology, Human Physiology Unit, Pavia University, Pavia 27100, Italy; Interuniversity Institute of Myology, Pavia University, Pavia 27100, Italy.
Corsetti
Giovanni
G
Human Anatomy Unit, Department of Biomedical Sciences and Biotechnologies, Brescia University, Brescia 25123, Italy.
Bottinelli
Roberto
R
Department of Physiology, Human Physiology Unit, Pavia University, Pavia 27100, Italy; Interuniversity Institute of Myology, Pavia University, Pavia 27100, Italy.
Carruba
Michele O
MO
Center for Study and Research on Obesity, Department of Pharmacology, Chemotherapy and Medical Toxicology, School of Medicine, Milan University, Milan 20129, Italy; Istituto Auxologico Italiano, Milan 20145, Italy.
Valerio
Alessandra
A
Center for Study and Research on Obesity, Department of Pharmacology, Chemotherapy and Medical Toxicology, School of Medicine, Milan University, Milan 20129, Italy; Pharmacology Unit, Department of Biomedical Sciences and Biotechnologies, Brescia University, Brescia 25123, Italy.
Nisoli
Enzo
E
Center for Study and Research on Obesity, Department of Pharmacology, Chemotherapy and Medical Toxicology, School of Medicine, Milan University, Milan 20129, Italy; Istituto Auxologico Italiano, Milan 20145, Italy. Electronic address: enzo.nisoli@unimi.it.
D000375:Aging / Q000187:drug effects; D000597:Amino Acids, Branched-Chain / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D008136:Longevity / Q000187:drug effects*; D051379:Mice; D008929:Mitochondria, Heart / Q000378:metabolism*; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000648:ultrastructure; D052250:Nitric Oxide Synthase Type III; D017382:Reactive Oxygen Species / Q000378:metabolism; D014018:Tissue Distribution
D000597:Amino Acids, Branched-Chain; D017382:Reactive Oxygen Species; D052250:Nitric Oxide Synthase Type III