Amino acid metabolism and regulatory effects in aging

Current Opinion in Clinical Nutrition and Metabolic Care

Volumn 11, Issue 1, 2008, Pages 45-49

  Timmerman, Kyle L ^a   Volpi, Elena ^a  

^a UNIVERSITY OF TEXAS MEDICAL BRANCH   (United States)

Author keywords

Aging; Amino acid; Leucine; Metabolism; Muscle protein; Sarcopenia

Indexed keywords

AMINO ACID; ESSENTIAL AMINO ACID; INSULIN; LEUCINE; MUSCLE PROTEIN;

AGING; AMINO ACID METABOLISM; ATTENUATION; CHRONIC DISEASE; DISEASE ASSOCIATION; DISEASE COURSE; EXERCISE; GERIATRICS; HUMAN; INSULIN RESISTANCE; MUSCLE ATROPHY; MUSCLE EXCITATION; MUSCLE METABOLISM; NUTRITION; PROTEIN INTAKE; PROTEIN METABOLISM; PROTEIN SYNTHESIS; REGULATORY MECHANISM; REVIEW; TRANSLATION INITIATION;

AGED; AGING; AMINO ACIDS; AMINO ACIDS, BRANCHED-CHAIN; AMINO ACIDS, ESSENTIAL; EXERCISE; HUMANS; MUSCLE PROTEINS; MUSCLE, SKELETAL; MUSCULAR ATROPHY;

EID: 37349084557     PISSN: 13631950     EISSN: 15353885     Source Type: Journal    
DOI: 10.1097/MCO.0b013e3282f2a592     Document Type: Review

References (58)

1. Welle S. Human protein metabolism. New York: Springer; 1999.
2. Matthews DE. Proteins and amino acids. In: Shils ME, editor. Modern nutrition in health and disease. Baltimore: Williams & Wilkins; 1999. pp. 11-48.
3. Reeds PJ, Fjeld CR, Jahoor F. Do the differences between the amino acid compositions of acute-phase and muscle proteins have a bearing on nitrogen loss in traumatic states? J Nutr 1994; 124:906-910.
4. Holloszy JO. The biology of aging. Mayo Clin Proc 2000; 75 (Suppl):S3-S8.
5. Melton LJ III, Khosla S, Riggs BL. Epidemiology of sarcopenia. Mayo Clin Proc 2000; 75 (Suppl):S10-S12.
6. Karakelides H, Sreekumaran NK. Sarcopenia of aging and its metabolic impact. Curr Top Dev Biol 2005; 68:123-148.
7. Janssen I, Heymsfield SB, Ross R. Low relative skeletal muscle mass (sarcopenia) in older persons is associated with functional impairment and physical disability. J Am Geriatr Soc 2002; 50:889-896.
8. Iannuzzi-Sucich M, Prestwood KM, Kenny AM. Prevalence of sarcopenia and predictors of skeletal muscle mass in healthy, older men and women. J Gerontol A Biol Sci Med Sci 2002; 57:M772-M777.
9. Sayer AA, Syddall HE, Martin HJ, et al. Falls, sarcopenia, and growth in early life: findings from the Hertfordshire cohort study. Am J Epidemiol 2006; 164:665-671.
10. Janssen I, Baumgartner RN, Ross R, et al. Skeletal muscle cutpoints associated with elevated physical disability risk in older men and women. Am J Epidemiol 2004; 159:413-421.
11. Baumgartner RN, Koehler KM, Gallagher D, et al. Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol 1998; 147:755-763.
12. Hasten DL, Pak-Loduca J, Obert KA, Yarasheski KE. Resistance exercise acutely increases MHC and mixed muscle protein synthesis rates in 78-84 and 23-32 yr olds. Am J Physiol Endocrinol Metab 2000; 278:E620-E626.
13. Volpi E, Mittendorfer B, Rasmussen BB, Wolfe RR. The response of muscle protein anabolism to combined hyperaminoacidemia and glucose-induced hyperinsulinemia is impaired in the elderly. J Clin Endocrinol Metab 2000; 85:4481-4490.
14. Volpi E, Sheffield-Moore M, Rasmussen BB, Wolfe RR. Basal muscle amino acid kinetics and protein synthesis in healthy young and older men. JAMA 2001; 286:1206-1212.
15. Welle S, Thornton C, Statt M. Myofibrillar protein synthesis in young and old human subjects after three months of resistance training. Am J Physiol 1995; 268 (3 Pt 1):E422-E427.
16. Yarasheski KE, Zachwieja JJ, Bier DM. Acute effects of resistance exercise on muscle protein synthesis rate in young and elderly men and women. Am J Physiol 1993; 265 (2 Pt 1):E210-E214.
17. Balagopal P, Rooyackers OE, Adey DB, et al. Effects of aging on in vivo synthesis of skeletal muscle myosin heavy-chain and sarcoplasmic protein in humans. Am J Physiol 1997; 273 (4 Pt 1):E790-E800.
18. Welle S, Thornton C, Jozefowicz R, Statt M. Myofibrillar protein synthesis in young and old men. Am J Physiol 1993; 264 (5 Pt 1):E693-E698.
19. Paddon-Jones D, Sheffield-Moore M, Zhang XJ, et al. Amino acid ingestion improves muscle protein synthesis in the young and elderly. Am J Physiol Endocrinol Metab 2004; 286:E321-E328.
20. Rennie MJ, Edwards RH, Halliday D, et al. Muscle protein synthesis measured by stable isotope techniques in man: the effects of feeding and fasting. Clin Sci (Lond) 1982; 63:519-523.
21. Biolo G, Tipton KD, Klein S, Wolfe RR. An abundant supply of amino acids enhances the metabolic effect of exercise on muscle protein. Am J Physiol 1997; 273 (1 Pt 1):E122-E129.
22. Symons TB, Schutzler SE, Cocke TL, et al. Aging does not impair the anabolic response to a protein-rich meal. Am J Clin Nutr 2007; 86:451-456. Aging does not impair the ability of a high-quality protein source (beef) to stimulate muscle protein synthesis.
23. Campbell WW, Trappe TA, Wolfe RR, Evans WJ. The recommended dietary allowance for protein may not be adequate for older people to maintain skeletal muscle. J Gerontol A Biol Sci Med Sci 2001; 56:M373-M380.
24. Thalacker-Mercer AE, Fleet JC, Craig BA, et al. Inadequate protein intake affects skeletal muscle transcript profiles in older humans. Am J Clin Nutr 2007; 85:1344-1352. Short-term inadequate protein intake elicits changes in muscle protein transcripts that may contribute to reduced muscle protein synthesis and muscle loss.
25. Fiatarone MA, O'Neill EF, Ryan ND, et al. Exercise training and nutritional supplementation for physical frailty in very elderly people. N Engl J Med 1994; 330:1769-1775.
26. Welle S, Thornton CA. High-protein meals do not enhance myofibrillar synthesis after resistance exercise in 62- to 75-yr-old men and women. Am J Physiol 1998; 274 (4 Pt 1):E677-E683.
27. Fiatarone Singh MA, Bernstein MA, Ryan AD, et al. The effect of oral nutritional supplements on habitual dietary quality and quantity in frail elders. J Nutr Health Aging 2000; 4:5-12.
28. Guillet C, Prod'homme M, Balage M, et al. Impaired anabolic response of muscle protein synthesis is associated with S6K1 dysregulation in elderly humans. FASEB J 2004; 18:1586-1587.
29. Rasmussen BB, Fujita S, Wolfe RR, et al. Insulin resistance of muscle protein metabolism in aging. FASEB J 2006; 20:768-769.
30. Fujita S, Rasmussen BB, Cadenas JG, et al. Aerobic exercise overcomes the age-related insulin resistance of muscle protein metabolism by improving endothelial function and Akt/mammalian target of rapamycin signaling. Diabetes 2007; 56:1615-1622. A single bout of aerobic exercise restores the anabolic response of muscle to insulin by improving endothelial function, anabolic signaling and amino acid availability for the muscle.
31. Fujita S, Rasmussen BB, Cadenas JG, et al. Effect of insulin on human skeletal muscle protein synthesis is modulated by insulin-induced changes in muscle blood flow and amino acid availability. Am J Physiol Endocrinol Metab 2006; 291:E745-E754.
32. Rasmussen BB, Wolfe RR, Volpi E. Oral and intravenously administered amino acids produce similar effects on muscle protein synthesis in the elderly. J Nutr Health Aging 2002; 6:358-362.
33. Volpi E, Ferrando AA, Yeckel CW, et al. Exogenous amino acids stimulate net muscle protein synthesis in the elderly. J Clin Invest 1998; 101:2000-2007.
34. Volpi E, Mittendorfer B, Wolf SE, Wolfe RR. Oral amino acids stimulate muscle protein anabolism in the elderly despite higher first-pass splanchnic extraction. Am J Physiol 1999; 277 (3 Pt 1):E513-E520.
35. Volpi E, Kobayashi H, Sheffield-Moore M, et al. Essential amino acids are primarily responsible for the amino acid stimulation of muscle protein anabolism in healthy elderly adults. Am J Clin Nutr 2003; 78:250-258.
36. Boirie Y, Gachon P, Beaufrere B. Splanchnic and whole-body leucine kinetics in young and elderly men. Am J Clin Nutr 1997; 65:489-495.
37. Anthony JC, Yoshizawa F, Anthony TG, et al. Leucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin-sensitive pathway. J Nutr 2000; 130:2413-2419.
38. Anthony JC, Anthony TG, Kimball SR, et al. Orally administered leucine stimulates protein synthesis in skeletal muscle of postabsorptive rats in association with increased eIF4F formation. J Nutr 2000; 130:139-145.
39. Garlick PJ. The role of leucine in the regulation of protein metabolism. J Nutr 2005; 135 (6 Suppl):1553S-1556S.
40. Anthony TG, Anthony JC, Yoshizawa F, et al. Oral administration of leucine stimulates ribosomal protein mRNA translation but not global rates of protein synthesis in the liver of rats. J Nutr 2001; 131:1171-1176.
41. Fujita S, Dreyer HC, Drummond MJ, et al. Nutrient signalling in the regulation of human muscle protein synthesis. J Physiol 2007; 582 (Pt 2):813-823. Ingestion of a leucine-enriched EAA/carbohydrate mixture promotes muscle protein synthesis via both an increased initiation of translation and an increased translation elongation.
42. Katsanos CS, Kobayashi H, Sheffield-Moore M, et al. Aging is associated with diminished accretion of muscle proteins after the ingestion of a small bolus of essential amino acids. Am J Clin Nutr 2005; 82:1065-1073.
43. Katsanos CS, Kobayashi H, Sheffield-Moore M, et al. A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly. Am J Physiol Endocrinol Metab 2006; 291:E381-E387. The muscle protein anabolic response to a small (submaximal) bolus of EAAs is blunted in older subjects, but can be restored by changing the EAA proportion in favor of leucine. Conversely, excess leucine has no additional anabolic effect in young subjects.
44. Paddon-Jones D, Sheffield-Moore M, Katsanos CS, et al. Differential stimulation of muscle protein synthesis in elderly humans following isocaloric ingestion of amino acids or whey protein. Exp Gerontol 2006; 41:215-219. Ingestion of EAAs stimulates muscle protein synthesis to a greater extent than ingestion of the same amount of whey protein, which contains non-EAAs. This confirms and highlights that EAAs are mainly responsible for the anabolic action of proteins.
45. Dardevet D, Sornet C, Bayle G, et al. Postprandial stimulation of muscle protein synthesis in old rats can be restored by a leucine-supplemented meal. J Nutr 2002; 132:95-100.
46. Rieu I, Sornet C, Bayle G, et al. Leucine-supplemented meal feeding for ten days beneficially affects postprandial muscle protein synthesis in old rats. J Nutr 2003; 133:1198-1205.
47. Rieu I, Balage M, Sornet C, et al. Increased availability of leucine with leucinerich whey proteins improves postprandial muscle protein synthesis in aging rats. Nutrition 2007; 23:323-331. Proteins rich in leucine provide a more potent stimulus for muscle protein synthesis than protein sources with a lower percentage of leucine in rats.
48. Rieu I, Balage M, Sornet C, et al. Leucine supplementation improves muscle protein synthesis in elderly men independently of hyperaminoacidaemia. J Physiol 2006; 575 (Pt 1):305-315. Leucine supplementation improves muscle protein synthesis in elderly men during feeding regardless of increases in the concentrations of other amino acids. This highlights how leucine can at least partially overcome the resistance of muscle proteins to the anabolic action of mixed feeding.
49. Koopman R, Verdijk L, Manders RJ, et al. Co-ingestion of protein and leucine stimulates muscle protein synthesis rates to the same extent in young and elderly lean men. Am J Clin Nutr 2006; 84:623-632. Coingestion of protein and leucine with carbohydrates stimulates muscle protein synthesis to the same extent in old as in young subjects.
50. Morais JA, Chevalier S, Gougeon R. Protein turnover and requirements in the healthy and frail elderly. J Nutr Health Aging 2006; 10:272-283. This is a recent review on protein requirements for healthy and frail older adults.
51. Morse MH, Haub MD, Evans WJ, Campbell WW. Protein requirement of elderly women: nitrogen balance responses to three levels of protein intake. J Gerontol A Biol Sci Med Sci 2001; 56:M724-M730.
52. Arnal MA, Mosoni L, Boirie Y, et al. Protein pulse feeding improves protein retention in elderly women. Am J Clin Nutr 1999; 69:1202-1208.
53. Arnal MA, Mosoni L, Dardevet D, et al. Pulse protein feeding pattern restores stimulation of muscle protein synthesis during the feeding period in old rats. J Nutr 2002; 132:1002-1008.
54. Engelen MP, Rutten EP, De Castro CL, et al. Supplementation of soy protein with branched-chain amino acids alters protein metabolism in healthy elderly and even more in patients with chronic obstructive pulmonary disease. Am J Clin Nutr 2007; 85:431-439. BCAA supplementation of soy protein improves the anabolic effect of soy protein on whole-body metabolism, particularly in elderly patients with chronic obstructive pulmonary disease.
55. Killewich LA, Tuvdendorj D, Bahadorani J, et al. Amino acids stimulate leg muscle protein synthesis in peripheral arterial disease. J Vasc Surg 2007; 45:554-559. Despite decreased blood flow, patients with peripheral arterial disease respond to the stimulatory effects of amino acids to the same extent as healthy elderly subjects.
56. Krebs M, Krssak M, Bernroider E, et al. Mechanism of amino acid-induced skeletal muscle insulin resistance in humans. Diabetes 2002; 51:599-605.
57. Tremblay F, Krebs M, Dombrowski L, et al. Overactivation of S6 kinase 1 as a cause of human insulin resistance during increased amino acid availability. Diabetes 2005; 54:2674-2684.
58. Wang X, Hu Z, Hu J, et al. Insulin resistance accelerates muscle protein degradation: activation of the ubiquitin-proteasome pathway by defects in muscle cell signaling. Endocrinology 2006; 147:4160-4168.