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Branched-Chain Amino Acid Supplementation Promotes Survival and Supports Cardiac and Skeletal Muscle Mitochondrial Biogenesis in Middle-Aged Mice
Open accessAbstract
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.
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“Interestingly, supplementation with a BCAA cocktail has been shown to promote well-being and extend the lifespan of mice (D'Antona et al., 2010) similar to the benefits conferred by caloric restriction (Guarente, 2008;Valerio et al., 2011).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as D'Antona et al., 2010
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“Mice supplemented with a BCAA-enriched cocktail exhibited improved physical endurance and an extended lifespan (335).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [335]
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“More recently, essential and/or branched chain amino acids have been shown to support cardiac and skeletal muscle through increased mitochondrial biogenesis and function in both mice and humans (D’Antona et al., 2010; Tatpati et al., 2010; Valerio et al., 2011).”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as D’Antona et al., 2010
In the citing paper
“This was confirmed in animal models with branched chain amino acid supplementation promoting mitochondrial biogenesis and inducing the expression of SIRT1 in skeletal muscle (D’Antona et al., 2010)”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as D’Antona et al., 2010
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Metadata
- Authors
- D'Antona, G., Ragni, M., Cardile, A., Tedesco, L., Dossena, M., Bruttini, F., Caliaro, F., Corsetti, G., Bottinelli, R., Carruba, M. O., Valerio, A., & Nisoli, E.
- Affiliations
- University of Milan (IT)
- University of Pavia (IT)
- University of Brescia (IT)
- Corresponding author
- Nisoli, Enzo
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 12
- Issue
- 4
- Pages
- 362-372
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W1998559329
- Cited by
- 568
- References
- 63
- Citations by year
- 2026: 22 · 2025: 34 · 2024: 27 · 2023: 48 · 2022: 51 · 2021: 52 · 2020: 42 · 2019: 32 · 2018: 50 · 2017: 39 · 2016: 36 · 2015: 31 · 2014: 32 · 2013: 25 · 2012: 24
- FWCI
- 7.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- branched-chain amino acids, mitochondrial biogenesis, longevity, lifespan extension, SIRT1, cardiomyocytes, skeletal muscle, reactive oxygen species, antioxidant defense, endothelial nitric oxide synthase, physical endurance, aging
- MeSH terms
- Aging, Amino Acids, Branched-Chain, Animals, Longevity, Mitochondria, Heart, Mitochondria, Muscle, Tissue Distribution, Reactive Oxygen Species, Muscle, Skeletal, Mice, Nitric Oxide Synthase Type III
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