Relationship between branched-chain amino acids and aging and health of the elderly_West China Medical Journal

Authors：

PU Lin , WEN Yue , LU Chunyan ,  CHEN Yi

Division of Gastrointestinal Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

CHEN Yi, Email: toddychan@163.com

Keywords：

Branched-chain amino acids; aging; skeletal muscle; metabolic diseases

DOI：

10.7507/1002-0179.202305132

Video：

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Skeletal muscle and metabolic function are important factors affecting the health status of the elderly. Branched-chain amino acids (BCAA) can improve muscle recovery, reduce muscle soreness after exercise, and BCAA can also enhance metabolic health, helping to regulate blood sugar levels and improve insulin sensitivity in the elderly. In addition, BCAA can improve cognitive function, reducing the risk of age-related cognitive decline. This article reviews the relationship between BCAA and aging, skeletal muscle, and metabolic diseases, explaining how BCAA can support and promote muscle mass and function in the elderly, as well as have a positive impact on metabolic health and cognitive function.

Citation： PU Lin, WEN Yue, LU Chunyan, CHEN Yi. Relationship between branched-chain amino acids and aging and health of the elderly. West China Medical Journal, 2024, 39(8): 1327-1332. doi: 10.7507/1002-0179.202305132 Copy

1.	温金红, 赵志明. 支链氨基酸在体育运动领域中的研究进展及展望. 湖北体育科技, 2023, 42(1): 59-63.
2.	Neinast M, Murashige D, Arany Z. Branched chain amino acids. Annu Rev Physiol, 2019, 81: 139-164.
3.	Bifari F, Nisoli E. Branched-chain amino acids differently modulate catabolic and anabolic states in mammals: a pharmacological point of view. Br J Pharmacol, 2017, 174(11): 1366-1377.
4.	Neinast MD, Jang C, Hui S, et al. Quantitative analysis of the whole-body metabolic fate of branched-chain amino acids. Cell Metab, 2019, 29(2): 417-429.e4.
5.	Holeček M, Mičuda S. Amino acid concentrations and protein metabolism of two types of rat skeletal muscle in postprandial state and after brief starvation. Physiol Res, 2017, 66(6): 959-967.
6.	Matthews DE. Observations of branched-chain amino acid administration in humans. J Nutr, 2005, 135(Suppl 6): 1580S-1584S.
7.	Zhang ZY, Monleon D, Verhamme P, et al. Branched-chain amino acids as critical switches in health and disease. Hypertension, 2018, 72(5): 1012-1022.
8.	Liu GY, Sabatini DM. mTOR at the nexus of nutrition, growth, ageing and disease. Nat Rev Mol Cell Biol, 2020, 21(4): 183-203.
9.	Wang TJ, Larson MG, Vasan RS, et al. Metabolite profiles and the risk of developing diabetes. Nat Med, 2011, 17(4): 448-453.
10.	Tian M, Heng J, Song H, et al. Dietary branched-chain amino acids regulate food intake partly through intestinal and hypothalamic amino acid receptors in piglets. J Agric Food Chem, 2019, 67(24): 6809-6818.
11.	Green CL, Lamming DW. Regulation of metabolic health by essential dietary amino acids. Mech Ageing Dev, 2019, 177: 186-200.
12.	Wolfe RR. Branched-chain amino acids and muscle protein synthesis in humans: myth or reality?. J Int Soc Sports Nutr, 2017, 14: 30.
13.	Biswas D, Duffley L, Pulinilkunnil T. Role of branched-chain amino acid-catabolizing enzymes in intertissue signaling, metabolic remodeling, and energy homeostasis. FASEB J, 2019, 33(8): 8711-8731.
14.	Shad BJ, Thompson JL, Breen L. Does the muscle protein synthetic response to exercise and amino acid-based nutrition diminish with advancing age? A systematic review. Am J Physiol Endocrinol Metab, 2016, 311(5): E803-E817.
15.	Le Couteur DG, Ribeiro R, Senior A, et al. Branched chain amino acids, cardiometabolic risk factors and outcomes in older men: the concord health and ageing in men project. J Gerontol A Biol Sci Med Sci, 2020, 75(10): 1805-1810.
16.	Swindell WR. Meta-analysis of 29 experiments evaluating the effects of rapamycin on life span in the laboratory mouse. J Gerontol A Biol Sci Med Sci, 2017, 72(8): 1024-1032.
17.	Selman C, Tullet JM, Wieser D, et al. , Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science, 2009, 326(5949): 140-144.
18.	Alvers AL, Wood MS, Hu D, et al. Autophagy is required for extension of yeast chronological life span by rapamycin. Autophagy, 2009, 5(6): 847-849.
19.	D’Antona G, Ragni M, Cardile A, et al. Branched-chain amino acid supplementation promotes survival and supports cardiac and skeletal muscle mitochondrial biogenesis in middle-aged mice. Cell Metab, 2010, 12(4): 362-372.
20.	Mansfeld J, Urban N, Priebe S, et al. Branched-chain amino acid catabolism is a conserved regulator of physiological ageing. Nat Commun, 2015, 6: 10043.
21.	Edwards C, Canfield J, Copes N, et al. Mechanisms of amino acid-mediated lifespan extension in Caenorhabditis elegans. BMC Genet, 2015, 16(1): 8.
22.	Juricic P, Grönke S, Partridge L. Branched-chain amino acids have equivalent effects to other essential amino acids on lifespan and aging-related traits in drosophila. J Gerontol A Biol Sci Med Sci, 2020, 75(1): 24-31.
23.	Ohtsuka H, Kato T, Sato T, et al. Leucine depletion extends the lifespans of leucine-auxotrophic fission yeast by inducing Ecl1 family genes via the transcription factor Fil1. Mol Genet Genomics, 2019, 294(6): 1499-1509.
24.	Solon-Biet SM, Cogger VC, Pulpitel T, et al. Branched chain amino acids impact health and lifespan indirectly via amino acid balance and appetite control. Nat Metab, 2019, 1(5): 532-545.
25.	Tournissac M, Vandal M, Tremblay C, et al. Dietary intake of branched-chain amino acids in a mouse model of Alzheimer’s disease: effects on survival, behavior, and neuropathology. Alzheimers Dement (N Y), 2018, 4: 677-687.
26.	Iwasa M, Kobayashi Y, Mifuji-Moroka R, et al. Branched-chain amino acid supplementation reduces oxidative stress and prolongs survival in rats with advanced liver cirrhosis. PLoS One, 2013, 8(7): e70309.
27.	Solon-Biet SM, McMahon AC, Ballard JW, et al. The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. Cell Metab, 2014, 19(3): 418-430.
28.	Horgusluoglu E, Neff R, Song WM, et al. Integrative metabolomics-genomics approach reveals key metabolic pathways and regulators of Alzheimer’s disease. Alzheimers Dement, 2022, 18(6): 1260-1278.
29.	Caldo-Silva A, Furtado GE, Chupel MU, et al. Effect of training-detraining phases of multicomponent exercises and BCAA supplementation on inflammatory markers and albumin levels in frail older persons. Nutrients, 2021, 13(4): 1106.
30.	Tsukishiro T, Shimizu Y, Higuchi K, et al. Effect of branched-chain amino acids on the composition and cytolytic activity of liver-associated lymphocytes in rats. J Gastroenterol Hepatol, 2000, 15(8): 849-859.
31.	Valerio A, D’Antona G, Nisoli E. Branched-chain amino acids, mitochondrial biogenesis, and healthspan: an evolutionary perspective. Aging (Albany NY), 2011, 3(5): 464-478.
32.	Richardson NE, Konon EN, Schuster HS, et al. Lifelong restriction of dietary branched-chain amino acids has sex-specific benefits for frailty and life span in mice. Nature Aging, 2021, 1(1): 73-86.
33.	Les I, Doval E, García-Martínez R, et al. Effects of branched-chain amino acids supplementation in patients with cirrhosis and a previous episode of hepatic encephalopathy: a randomized study. Am J Gastroenterol, 2011, 106(6): 1081-1088.
34.	Calles-Escandon J, Cunningham J, Felig P. The plasma amino acid response to cafeteria feeding in the rat: influence of hyperphagia, sucrose intake, and exercise. Metabolism, 1984, 33(4): 364-368.
35.	Fang X, Miao R, Wei J, et al. Advances in multi-omics study of biomarkers of glycolipid metabolism disorder. Comput Struct Biotechnol J, 2022, 20: 5935-5951.
36.	Dhakan DB, Maji A, Sharma AK, et al. The unique composition of Indian gut microbiome, gene catalogue, and associated fecal metabolome deciphered using multi-omics approaches. Gigascience, 2019, 8(3): giz004.
37.	Lin C, Sun Z, Mei Z, et al. The causal associations of circulating amino acids with blood pressure: a Mendelian randomization study. BMC Med, 2022, 20(1): 414.
38.	Solon-Biet SM, Griffiths L, Fosh S, et al. Meta-analysis links dietary branched-chain amino acids to metabolic health in rodents. BMC Biol, 2022, 20(1): 19.
39.	Soleimani E, Rashnoo F, Farhangi MA, et al. Dietary branched-chain amino acids intake, glycemic markers, metabolic profile, and anthropometric features in a community-based sample of overweight and obese adults. BMC Endocr Disord 2023, 23(1): 205.

1. 温金红, 赵志明. 支链氨基酸在体育运动领域中的研究进展及展望. 湖北体育科技, 2023, 42(1): 59-63.
2. Neinast M, Murashige D, Arany Z. Branched chain amino acids. Annu Rev Physiol, 2019, 81: 139-164.
3. Bifari F, Nisoli E. Branched-chain amino acids differently modulate catabolic and anabolic states in mammals: a pharmacological point of view. Br J Pharmacol, 2017, 174(11): 1366-1377.
4. Neinast MD, Jang C, Hui S, et al. Quantitative analysis of the whole-body metabolic fate of branched-chain amino acids. Cell Metab, 2019, 29(2): 417-429.e4.
5. Holeček M, Mičuda S. Amino acid concentrations and protein metabolism of two types of rat skeletal muscle in postprandial state and after brief starvation. Physiol Res, 2017, 66(6): 959-967.
6. Matthews DE. Observations of branched-chain amino acid administration in humans. J Nutr, 2005, 135(Suppl 6): 1580S-1584S.
7. Zhang ZY, Monleon D, Verhamme P, et al. Branched-chain amino acids as critical switches in health and disease. Hypertension, 2018, 72(5): 1012-1022.
8. Liu GY, Sabatini DM. mTOR at the nexus of nutrition, growth, ageing and disease. Nat Rev Mol Cell Biol, 2020, 21(4): 183-203.
9. Wang TJ, Larson MG, Vasan RS, et al. Metabolite profiles and the risk of developing diabetes. Nat Med, 2011, 17(4): 448-453.
10. Tian M, Heng J, Song H, et al. Dietary branched-chain amino acids regulate food intake partly through intestinal and hypothalamic amino acid receptors in piglets. J Agric Food Chem, 2019, 67(24): 6809-6818.
11. Green CL, Lamming DW. Regulation of metabolic health by essential dietary amino acids. Mech Ageing Dev, 2019, 177: 186-200.
12. Wolfe RR. Branched-chain amino acids and muscle protein synthesis in humans: myth or reality?. J Int Soc Sports Nutr, 2017, 14: 30.
13. Biswas D, Duffley L, Pulinilkunnil T. Role of branched-chain amino acid-catabolizing enzymes in intertissue signaling, metabolic remodeling, and energy homeostasis. FASEB J, 2019, 33(8): 8711-8731.
14. Shad BJ, Thompson JL, Breen L. Does the muscle protein synthetic response to exercise and amino acid-based nutrition diminish with advancing age? A systematic review. Am J Physiol Endocrinol Metab, 2016, 311(5): E803-E817.
15. Le Couteur DG, Ribeiro R, Senior A, et al. Branched chain amino acids, cardiometabolic risk factors and outcomes in older men: the concord health and ageing in men project. J Gerontol A Biol Sci Med Sci, 2020, 75(10): 1805-1810.
16. Swindell WR. Meta-analysis of 29 experiments evaluating the effects of rapamycin on life span in the laboratory mouse. J Gerontol A Biol Sci Med Sci, 2017, 72(8): 1024-1032.
17. Selman C, Tullet JM, Wieser D, et al. , Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science, 2009, 326(5949): 140-144.
18. Alvers AL, Wood MS, Hu D, et al. Autophagy is required for extension of yeast chronological life span by rapamycin. Autophagy, 2009, 5(6): 847-849.
19. D’Antona G, Ragni M, Cardile A, et al. Branched-chain amino acid supplementation promotes survival and supports cardiac and skeletal muscle mitochondrial biogenesis in middle-aged mice. Cell Metab, 2010, 12(4): 362-372.
20. Mansfeld J, Urban N, Priebe S, et al. Branched-chain amino acid catabolism is a conserved regulator of physiological ageing. Nat Commun, 2015, 6: 10043.
21. Edwards C, Canfield J, Copes N, et al. Mechanisms of amino acid-mediated lifespan extension in Caenorhabditis elegans. BMC Genet, 2015, 16(1): 8.
22. Juricic P, Grönke S, Partridge L. Branched-chain amino acids have equivalent effects to other essential amino acids on lifespan and aging-related traits in drosophila. J Gerontol A Biol Sci Med Sci, 2020, 75(1): 24-31.
23. Ohtsuka H, Kato T, Sato T, et al. Leucine depletion extends the lifespans of leucine-auxotrophic fission yeast by inducing Ecl1 family genes via the transcription factor Fil1. Mol Genet Genomics, 2019, 294(6): 1499-1509.
24. Solon-Biet SM, Cogger VC, Pulpitel T, et al. Branched chain amino acids impact health and lifespan indirectly via amino acid balance and appetite control. Nat Metab, 2019, 1(5): 532-545.
25. Tournissac M, Vandal M, Tremblay C, et al. Dietary intake of branched-chain amino acids in a mouse model of Alzheimer’s disease: effects on survival, behavior, and neuropathology. Alzheimers Dement (N Y), 2018, 4: 677-687.
26. Iwasa M, Kobayashi Y, Mifuji-Moroka R, et al. Branched-chain amino acid supplementation reduces oxidative stress and prolongs survival in rats with advanced liver cirrhosis. PLoS One, 2013, 8(7): e70309.
27. Solon-Biet SM, McMahon AC, Ballard JW, et al. The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. Cell Metab, 2014, 19(3): 418-430.
28. Horgusluoglu E, Neff R, Song WM, et al. Integrative metabolomics-genomics approach reveals key metabolic pathways and regulators of Alzheimer’s disease. Alzheimers Dement, 2022, 18(6): 1260-1278.
29. Caldo-Silva A, Furtado GE, Chupel MU, et al. Effect of training-detraining phases of multicomponent exercises and BCAA supplementation on inflammatory markers and albumin levels in frail older persons. Nutrients, 2021, 13(4): 1106.
30. Tsukishiro T, Shimizu Y, Higuchi K, et al. Effect of branched-chain amino acids on the composition and cytolytic activity of liver-associated lymphocytes in rats. J Gastroenterol Hepatol, 2000, 15(8): 849-859.
31. Valerio A, D’Antona G, Nisoli E. Branched-chain amino acids, mitochondrial biogenesis, and healthspan: an evolutionary perspective. Aging (Albany NY), 2011, 3(5): 464-478.
32. Richardson NE, Konon EN, Schuster HS, et al. Lifelong restriction of dietary branched-chain amino acids has sex-specific benefits for frailty and life span in mice. Nature Aging, 2021, 1(1): 73-86.
33. Les I, Doval E, García-Martínez R, et al. Effects of branched-chain amino acids supplementation in patients with cirrhosis and a previous episode of hepatic encephalopathy: a randomized study. Am J Gastroenterol, 2011, 106(6): 1081-1088.
34. Calles-Escandon J, Cunningham J, Felig P. The plasma amino acid response to cafeteria feeding in the rat: influence of hyperphagia, sucrose intake, and exercise. Metabolism, 1984, 33(4): 364-368.
35. Fang X, Miao R, Wei J, et al. Advances in multi-omics study of biomarkers of glycolipid metabolism disorder. Comput Struct Biotechnol J, 2022, 20: 5935-5951.
36. Dhakan DB, Maji A, Sharma AK, et al. The unique composition of Indian gut microbiome, gene catalogue, and associated fecal metabolome deciphered using multi-omics approaches. Gigascience, 2019, 8(3): giz004.
37. Lin C, Sun Z, Mei Z, et al. The causal associations of circulating amino acids with blood pressure: a Mendelian randomization study. BMC Med, 2022, 20(1): 414.
38. Solon-Biet SM, Griffiths L, Fosh S, et al. Meta-analysis links dietary branched-chain amino acids to metabolic health in rodents. BMC Biol, 2022, 20(1): 19.
39. Soleimani E, Rashnoo F, Farhangi MA, et al. Dietary branched-chain amino acids intake, glycemic markers, metabolic profile, and anthropometric features in a community-based sample of overweight and obese adults. BMC Endocr Disord 2023, 23(1): 205.

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Relationship between branched-chain amino acids and aging and health of the elderly

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