The effect of branched chain amino acids on skeletal muscle mitochondrial function in young and elderly adults
Open accessAbstract
Context: A reduction in maximal mitochondrial ATP production rate (MAPR) and mitochondrial DNA (mtDNA) abundance occurs with age in association with muscle weakness and reduced endurance in elderly people. Branched chain amino acids (BCAA) have been extensively used to improve physical performance. Objective: The objective was to determine whether an 8-h infusion of BCAA enhances MAPR equally in healthy young and elderly adults. Methods: Using a crossover study design, we compared the effect BCAA vs. saline infusion in 12 young (23.0 ± 0.8 yr) and 12 elderly (70.7 ± 1.1 yr) participants matched for sex and body mass index. Skeletal muscle MAPR and mtDNA abundance were measured in muscle biopsy samples obtained before and at the end of the 8-h infusion. Results: In young participants, MAPR with the substrates glutamate plus malate (supplying electrons to complex I) and succinate plus rotenone (complex II) increased in response to BCAA infusion, relative to a decline in MAPR in response to the saline infusion. In contrast, MAPR was unaffected by BCAA infusion in the elderly participants. Moreover, mtDNA abundance was lower in the elderly compared with the young participants but was unaffected by the BCAA infusion. Insulin and C-peptide concentrations declined over time during the saline infusion, but these declines were prevented by the BCAA infusion. Conclusions: BCAA increased skeletal muscle MAPR in the young participants in comparison with saline, but this effect was not seen in the elderly participants indicating, that unlike in the young, BCAA does not increase muscle mitochondrial function in the elderly.
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Maximal mitochondrial ATP production rates in response to a supply of complex I substrates are lower in older than in younger adults.
“These findings are consistent with recent data indicating that maximal mitochondrial ATP production rates in response to a supply of complex I substrates are lower in older than in younger adults (35, 39).”
From Combined Training Enhances Skeletal Muscle Mitochondrial Oxidative Capacity Independent of Age (2015) · cites this paper as [39]
Essential and/or branched chain amino acids support cardiac and skeletal muscle through increased mitochondrial biogenesis and function in both mice and humans.
“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 Tatpati et al., 2010
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Cites
Mitochondrial dysfunction in the elderly: possible role in insulin resistance
Petersen, K. F., Befroy, D., Dufour, S., Dziura, J., Ariyan, C., Rothman, D. L., DiPietro, L., Cline, G. W., & Shulman, G. I. (2003) · Science · doi:10.1126/science.1082889 · Cited by 2,107 · see citing works
Decline in skeletal muscle mitochondrial function with aging in humans
Short, K. R., Bigelow, M. L., Kahl, J., Singh, R., Coenen-Schimke, J., Raghavakaimal, S., & Nair, K. S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501559102 · Cited by 1,333 · see citing works
Self-citationAnabolic signaling deficits underlie amino acid resistance of wasting, aging muscle
Cuthbertson, D., Smith, K., Babraj, J., Leese, G., Waddell, T., Atherton, P., Wackerhage, H., Taylor, P. M., & Rennie, M. J. (2005) · The FASEB Journal · doi:10.1096/fj.04-2640fje · Cited by 1,211 · see citing works
Volpi, E., Kobayashi, H., Sheffield-Moore, M., Mittendorfer, B., & Wolfe, R. R. (2003) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/78.2.250 · Cited by 846 · see citing works
Stimulation of insulin secretion by amino acids.
Floyd, J. C., Fajans, S. S., Conn, J. W., Knopf, R. F., & Rull, J. (1966) · Journal of Clinical Investigation · doi:10.1172/jci105456 · Cited by 727 · see citing works
Temporal analysis of phosphotyrosine-dependent signaling networks by quantitative proteomics
Blagoev, B., Ong, S., Kratchmarova, I., & Mann, M. (2004) · Nature Biotechnology · doi:10.1038/nbt1005 · Cited by 684 · see citing works
Short, K. R., Vittone, J. L., Bigelow, M. L., Proctor, D. N., Rizza, R. A., Coenen-Schimke, J. M., & Nair, K. S. (2003) · Diabetes · doi:10.2337/diabetes.52.8.1888 · Cited by 631 · see citing works
Self-citationIII, L. J. M., Khosla, S., Crowson, C. S., O'Connor, M. K., O'Fallon, W. M., & Riggs, B. L. (2000) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2000.tb04719.x · Cited by 598 · see citing works
Effect of age on <i>in vivo</i> rates of mitochondrial protein synthesis in human skeletal muscle
Rooyackers, O. E., Adey, D. B., Ades, P. A., & Nair, K. S. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.26.15364 · Cited by 564 · see citing works
Self-citationStump, C. S., Short, K. R., Bigelow, M. L., Schimke, J. M., & Nair, K. S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1332551100 · Cited by 477 · see citing works
Self-citationExogenous amino acids stimulate net muscle protein synthesis in the elderly.
Volpi, E., Ferrando, A. A., Yeckel, C. W., Tipton, K. D., & Wolfe, R. R. (1998) · Journal of Clinical Investigation · doi:10.1172/jci939 · Cited by 390 · see citing works
The Role of Leucine in Weight Loss Diets and Glucose Homeostasis
Layman, D. K. (2003) · Journal of Nutrition · doi:10.1093/jn/133.1.261s · Cited by 383 · see citing works
Age, Obesity, and Sex Effects on Insulin Sensitivity and Skeletal Muscle Mitochondrial Function
Karakelides, H., Irving, B. A., Short, K. R., O'Brien, P., & Nair, K. S. (2010) · Diabetes · doi:10.2337/db09-0591 · Cited by 293 · see citing works
Self-citationDillon, E. L., Sheffield‐Moore, M., Paddon‐Jones, D., Gilkison, C. R., Sanford, A. P., Casperson, S. L., Jiang, J., Chinkes, D. L., & Urban, R. J. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1564 · Cited by 276 · see citing works
Glucagon-stimulating activity of 20 amino acids in dogs
Rocha, D. M., Faloona, G. R., & Unger, R. H. (1972) · Journal of Clinical Investigation · doi:10.1172/jci107046 · Cited by 268 · see citing works
Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients.
Nair, K. S., Ford, G. C., Ekberg, K., Fernqvist-Forbes, E., & Wahren, J. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118000 · Cited by 239 · see citing works
Self-citationThe Significance of Sarcopenia in Old Age
Dutta, C., & Hadley, E. C. (1995) · The Journals of Gerontology Series A · doi:10.1093/gerona/50a.special_issue.1 · Cited by 228 · see citing works
JENSEN, M. D., Kanaley, J. A., Roust, L. R., O’Brien, P. C., BRAUN, J. S., DUNN, W. L., & Wahner, H. W. (1993) · Mayo Clinic Proceedings · doi:10.1016/s0025-6196(12)60695-8 · Cited by 213 · see citing works
mTOR-mediated regulation of translation factors by amino acids
Proud, C. G. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.07.015 · Cited by 205 · see citing works
Koopman, R., Verdijk, L. B., MANDERS, R. J. F., Gijsen, A. P., Gorselink, M., Pijpers, E., Wagenmakers, A. J. M., & van Loon, L. J. C. (2006) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/84.3.623 · Cited by 202 · see citing works
Kuhara, T., Ikeda, S., Ohneda, A., & Sasaki, Y. (1991) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1991.260.1.e21 · Cited by 167 · see citing works
Fujita, S., Glynn, E. L., Timmerman, K. L., Rasmussen, B. B., & Volpi, E. (2009) · Diabetologia · doi:10.1007/s00125-009-1430-8 · Cited by 164 · see citing works
Effect of Infused Branched-Chain Amino Acids on Muscle and Whole-Body Amino Acid Metabolism in Man
Louard, R. J., Barrett, E. J., & Gelfand, R. A. (1990) · Clinical Science · doi:10.1042/cs0790457 · Cited by 157 · see citing works
Regulation of protein synthesis by branched-chain amino acids
Kimball, S., & Jefferson, L. (2001) · Current opinion in clinical nutrition and metabolic care · doi:10.1097/00075197-200101000-00008 · Cited by 138 · see citing works
Use of amino acids as growth hormone-releasing agents by athletes
Chromiak, J. A., & António, J. (2002) · Nutrition · doi:10.1016/s0899-9007(02)00807-9 · Cited by 129 · see citing works
Evidence for a catabolic role of glucagon during an amino acid load.
Charlton, M., Adey, D., & Nair, K. S. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118782 · Cited by 128 · see citing works
Self-citationKarakelides, H., Asmann, Y. W., Bigelow, M. L., Short, K. R., Dhatariya, K., Coenen-Schimke, J., Kahl, J., Mukhopadhyay, D., & Nair, K. S. (2007) · Diabetes · doi:10.2337/db07-0378 · Cited by 123 · see citing works
Self-citationOvernight branched-chain amino acid infusion causes sustained suppression of muscle proteolysis
Louard, R. J., Barrett, E. J., & Gelfand, R. (1995) · Metabolism · doi:10.1016/0026-0495(95)90047-0 · Cited by 105 · see citing works
Heated dorsal hand vein sampling for metabolic studies: a reappraisal
Copeland, K. C., Kenney, F. A., & Nair, K. S. (1992) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1992.263.5.e1010 · Cited by 97 · see citing works
Self-citationShort, K. R., Nygren, J., Barazzoni, R., Levine, J. A., & Nair, K. S. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.280.5.e761 · Cited by 90 · see citing works
Self-citationEffect of nutritional supplements on wound healing in home-nursed elderly: A randomized trial
Collins, C. E., Kershaw, J., & Brockington, S. (2005) · Nutrition · doi:10.1016/j.nut.2004.10.006 · Cited by 81 · see citing works
Amino Acids as Regulators of Gene Expression at the Level of mRNA Translation
Jefferson, L. S., & Kimball, S. R. (2003) · Journal of Nutrition · doi:10.1093/jn/133.6.2046s · Cited by 76 · see citing works
A sensitive method for measuring ATP-formation in rat muscle mitochondria
Wibom, R., Lundin, A., & Hultman, E. (1990) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365519009089146 · Cited by 74 · see citing works
Effect of leucine on amino acid and glucose metabolism in humans
Nair, K. S., Matthews, D. E., Welle, S. L., & Braiman, T. (1992) · Metabolism · doi:10.1016/0026-0495(92)90057-h · Cited by 66 · see citing works
Self-citationGuillet, C., Zangarelli, A., Mishellany‐Dutour, A., Rousset, P., Sornet, C., Dardevet, D. P., & Boirie, Y. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2004.02.011 · Cited by 49 · see citing works
Anabolic action of insulin on skin wound protein is augmented by exogenous amino acids
Zhang, X., Chinkes, D. L., Irtun, Ø., & Wolfe, R. R. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00361.2001 · Cited by 47 · see citing works
Quantitative protein microarrays for time‐resolved measurements of protein phosphorylation
Korf, U., Derdak, S. V., Tresch, A., Henjes, F., Schumacher, S., Schmidt, C., Hahn, B., Lehmann, W. D., Poustka, A., Beißbarth, T., et al. (2008) · PROTEOMICS · doi:10.1002/pmic.200800112 · Cited by 31 · see citing works
Tabaru, A. (1998) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365529850171521 · Cited by 17 · see citing works
Nair, K. S., Welle, S. L., & Tito, J. (1990) · Diabetes · doi:10.2337/diab.39.3.376 · Cited by 16 · see citing works
Self-citationProtein and Amino Acid Supplementation in Athletes
Armsey, T. D., & Grime, T. E. (2002) · Current Sports Medicine Reports · doi:10.1249/00149619-200208000-00010 · Cited by 5 · see citing works
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Irving, B. A., Lanza, I. R., Henderson, G. C., Rao, R. R., Spiegelman, B. M., & Nair, K. S. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-3081 · Cited by 139 · see citing works
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Porter, C., Hurren, N. M., Cotter, M. V., Bhattarai, N., Reidy, P. T., Dillon, E. L., Durham, W. J., Tuvdendorj, D., Sheffield-Moore, M., Volpi, E., et al. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00125.2015 · Cited by 134 · see citing works
Fouré, A., & Bendahan, D. (2017) · Nutrients · doi:10.3390/nu9101047 · Cited by 116 · see citing works
Robinson, M. M., Soop, M., Sohn, T. S., Morse, D. M., Schimke, J. M., Klaus, K. A., & Nair, K. S. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-2736 · Cited by 59 · see citing works
Self-citation
- Authors
- Tatpati, L. L., Irving, B. A., Tom, A., Bigelow, M. L., Klaus, K., Short, K. R., & Nair, K. S.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Nair, K. Sreekumaran
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2010-02-01
- Volume
- 95
- Issue
- 2
- Pages
- 894-902
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC2840857
- OpenAlex
- W2111271771
- Cited by
- 44
- References
- 40
- Citations by year
- 2025: 2 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 7 · 2015: 6 · 2014: 2 · 2013: 2 · 2012: 1
- FWCI
- 0.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Civil War Book Review (submittedVersion)
- Funders
- Mayo Clinic (UL1 RR024150, 55905, RR024150, KL2 RR024151)
- National Institutes of Health (RR024150, UL1-RR-024150-01, RR024150-01)
- National Institute on Aging (R01‐AG09531, R01AG009531)
- National Center for Research Resources (RR-024150, RR‐024150‐01, KL2RR024151, RR024151, RR024151-01, UL1RR024150)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- branched-chain amino acids, skeletal muscle mitochondrial function, aging, older adults, muscle weakness, insulin, C-peptide, glutamate-malate
- MeSH terms
- Adenosine Triphosphate, Adolescent, Adult, Aged, Aged, 80 and over, Amino Acids, Branched-Chain, Blood Glucose, C-Peptide, DNA, Mitochondrial, Fatty Acids, Nonesterified, Female, Glucagon, Humans, Insulin, Male, Mitochondria, Muscle, Muscle, Skeletal, Young Adult
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