Abstract
The aetiology of sarcopenia is multifactorial but still poorly understood while the sequelae of this phenomenon, i.e. loss of independence and metabolic complications, represent a major public health. The most evident metabolic explanation for muscle decline in elderly people is an imbalance between protein synthesis abd breakdown rates but other causes like neurodegenerative processes, reduction in anabolic hormone productions or sensitivity such as insulin, growth and sex hormones, dysregulation of cytokine secretions, modification in the response to inflammatory events, inadequate nutritional intakes and sedentarity lifestyle are involved. Consequently, the age-related loss of muscle mass could be counteracted by adequate metabolic interventions including nutritional intakes or exercise training. Recent observations clearly show that changes in quantitative as well as qualitative intakes of dietary protein are able to counteract some pathophysiological processes related to muscle loss progression. Other strategies including changes in daily protein pattern, the speed of protein digestion or specific amino acids supplementation may be beneficial to improve short term muscle anabolic response in elderly people. The beneficial impact of resistance or endurance training on muscle mass and function is highlighted in many studies suggesting that the potential anabolic response to exercise still remains despite a lesser metabolic response to nutrients. Thus a multimodal approach combining nutrition, exercise, hormones, specific anabolic drugs may an innovative treatment for limiting the development of sarcopenia with aging.
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Janssen I, Shepard DS, Katzmarzyk PT, Roubenoff R. The healthcare costs of sarcopenia in the United States. J Am Geriatr Soc 2004, 52:80–85.
Walrand S, Boirie Y: Optimizing protein intake in aging. Curr Opin Clin Nutr Metab Care 2005, 8:89–94
Zadik Z, Chalew SA, McCarter RJ Jr., Meistas M, Kowarski AA. The influence of age on the 24-hour integrated concentration of growth hormone in normal individuals. J Clin Endocrinol Metab 1985;60:513–516
Rudman D, Feller A, Nagraj H, et al. Effects of human growth hormone in men over 60 years old. N Engl J Med 1990;323:1–6
Papadakis MA, Grady D, Black D, et al. Growth hormone replacement in healthy older men improves body composition but not functional ability. Ann Intern Med 1996;124:708–716.
Nass R, Thorner M.O. Impact of the GH-cortisol ratio on the age-dependent changes in body composition. Growth Hormone & IGF Research 2002, 12, 147–161
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
Fong Y, Moldawer LL, Marano M, Wei H, Barber A, Manogue K, Tracey KJ, Kuo G, Fischman DA, Cerami A, et al. Cachectin/TNF or IL-1 alpha induces cachexia with redistribution of body proteins. Am J Physiol. 1989;256(3 Pt 2):R659–R665
Lang CH, Frost RA, Nairn AC, MacLean DA, Vary TC. TNF-alpha impairs heart and skeletal muscle protein synthesis by altering translation initiation. Am J Physiol Endocrinol Metab. 2002 Feb;282(2):E336–E347
Garcia-Martinez C, Agell N, Llovera M, Lopez-Soriano FJ, Argiles JM. Tumour necrosis factor-alpha increases the ubiquitinization of rat skeletal muscle proteins. FEBS Lett. 1993;323(3):211–214
Zoico E, Roubenoff R. The role of cytokines in regulating protein metabolism and muscle function. Nutr Rev. 2002;60(2):39–51
Biolo G, Declan Fleming RY, Wolfe RR. Physiologic hyperinsulinemia stimulates protein synthesis and enhances transport of selected amino acids in human skeletal muscle. J Clin Invest. 1995 Feb;95(2):811–819.
Guillet C, Zangarelli A, Gachon P, Morio B, Giraudet C, Rousset P, Boirie Y. Whole body protein breakdown is less inhibited by insulin, but still responsive to amino acid, in nondiabetic elderly subjects. J Clin Endocrinol Metab. 2004 Dec;89(12):6017–6024
Carbo N, Ribas V, Busquets S, Alvarez B, Lopez-Soriano FJ, Argiles JM. Short-term effects of leptin on skeletal muscle protein metabolism in the rat. J Nutr Biochem. 2000;11(9):431–435
Walrand S., Vasson M-P., Lesourd B. The role of nutrition in immunity of the aged. In: Gut flora, nutrition and immunity. Perdigon G. and Fuller R. (Eds). Blackwells, Oxford, 2003, pp 237–269
Short KR, Nair KS. The effect of age on protein metabolism. Curr Opin Clin Nutr Metab Care 2000;3:39–44.
Volpi E, Ferrando AA, Yeckel CW, Tipton KD, Wolfe RR. Exogenous amino acids stimulate net muscle protein synthesis in the elderly. J Clin Invest 1998;101:2000–2007.
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:E513–E520.
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.
Volpi E, Kobayashi H, Sheffield-Moore M, Mittendorfer B, Wolfe RR. 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
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.
Mosoni L, Valluy MC, Serrurier B, et al. Altered response of protein synthesis to nutritional state and endurance training in old rats. Am J Physiol 1995;268:E328–E335.
FAO/WHO/UNU: Energy and protein requirements. Report of a joint expert consultation. World Health Organ Tech Rep Ser 1985:724
Campbell WW, Crim MC, Dallal GE et al.: Increased protein requirements in elderly people: new data and retrospective reassessments. Am J Clin Nutr 1994, 60:501–509
Campbell WW, Evans WJ: Protein requirements of elderly people. Eur J Clin Nutr 1996, 50Suppl 1:S180–S183; discussion S183–5
Millward DJ, Fereday A, Gibson N et al.: Aging, protein requirements, and protein turnover. Am J Clin Nutr 1997, 66:774–786
Millward DJ: Optimal intakes of protein in the human diet. Proc Nutr Soc 1999, 58:403–413
Gaillard C, Alix E, Boirie Y, Berrut G, Ritz P. Are Elderly Hospitalized Patients Getting Enough Protein? J Am Geriatr Soc 2008, 56:1045–1049
Pannemans DL, Halliday D, Westerterp KR: Whole-body protein turnover in elderly men and women: responses to two protein intakes. Am J Clin Nutr 1995, 61:33–38
Walrand S., Short K., Bigelow M., Nair KS. Effect of a high protein diet on insulin sensitivity, leucine kinetics, and renal function in healthy elderly humans. Am J Physiol Endoc Metab 2008
Castaneda C, Dolnikowski GG, Dallal GE et al.: Protein turnover and energy metabolism of elderly women fed a low-protein diet. Am J Clin Nutr 1995, 62:40–48
Castaneda C, Charnley JM, Evans WJ et al.: Elderly women accommodate to a lowprotein diet with losses of body cell mass, muscle function, and immune response. Am J Clin Nutr 1995, 62:30–39
Houston DK, Nicklas BJ, Ding J, Harris TB, Tylavsky FA, Newman AB, Lee JS, Sahyoun NR, Visser M, Kritchevsky SB. Dietary protein intake is associated with lean mass change in older, community-dwelling adults: the Health, Aging, and Body Composition (Health ABC) Study. Am J Clin Nutr 2008;87:150–155
Pannemans DL, Wagenmakers AJ, Westerterp KR et al.: Effect of protein source and quantity on protein metabolism in elderly women. Am J Clin Nutr 1998, 68:1228–1235
Boirie Y, Dangin M, Gachon P et al.: Slow and fast dietary proteins differently modulate postprandial protein accretion. Proc Natl Acad Sci U S A 1997, 94:14930–14935
Dangin M, Guillet C, Garcia-Rodenas C et al.: The rate of protein digestion affects protein gain differently during aging in humans. J Physiol 2003, 549:635–644
Paddon-Jones D, Sheffield-Moore M, Katsanos CS, Zhang XJ, Wolfe RR. Differential stimulation of muscle protein synthesis in elderly humans following isocaloric ingestion of amino acids or whey protein. Exp Gerontol 2006;41:215–219
Paddon-Jones D, Short KR, Campbell WW, Volpi E, Wolfe RR. Role of dietary protein in the sarcopenia of aging. Am J Clin Nutr 2008;87(suppl):1562S–1566S
Dardevet D, Sornet C, Balage M et al.: Stimulation of in vitro rat muscle protein synthesis by leucine decreases with age. J Nutr 2000, 130:2630–2635
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
Guillet C, Zangarelli A, Mishellany A et al.: Mitochondrial and sarcoplasmic proteins, but not myosin heavy chain, are sensitive to leucine supplementation in old rat skeletal muscle. Exp Gerontol 2004, 39:745–751
Anthony JC, Anthony TG, Kimball SR et al.: Signaling pathways involved in translational control of protein synthesis in skeletal muscle by leucine. J Nutr 2001, 131:856S–860S
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
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
Arnal MA, Mosoni L, Boirie Y et al.: Protein turnover modifications induced by the protein feeding pattern still persist after the end of the diets. Am J Physiol Endocrinol Metab 2000, 278:E902–E909
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
Klitgaard H, Mantoni M, Schiaffino S, et al. Function, morphology and protein expression of ageing skeletal muscle: a cross-sectional study of elderly men with different training backgrounds. Acta Physiol Scand 1990;140:41–54.
Evans WJ, Campbell WW. Sarcopenia and age-related changes in body composition and functional capacity. J Nutr 1993;123:465–468.
Hurley BF, Hagberg JM. Optimizing health in older persons: aerobic or strength training? Exerc Sport Sci Rev 1998;26:61–89.
Roubenoff R. Sarcopenia: a major modifiable cause of frailty in the elderly. J Nutr Health Aging 2000;4:140–142.
Schulte JN, Yarasheski KE. Effects of resistance training on the rate of muscle protein synthesis in frail elderly people. Int J Sport Nutr Exerc Metab 2001;11Suppl:S111–S118.
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:E210–E214.
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:E422–E427.
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.
Balagopal P, Schimke JC, Ades P, Adey D, Nair KS. Age effect on transcript levels and synthesis rate of muscle MHC and response to resistance exercise. Am J Physiol Endocrinol Metab 2001;280:E203–E208.
Williamson DL, Godard MP, Porter DA, Costill DL, Trappe SW. Progressive resistance training reduces myosin heavy chain coexpression in single muscle fibers from older men. J Appl Physiol 2000;88:627–633.
Welle S, Bhatt K, Thornton CA. Stimulation of myofibrillar synthesis by exercise is mediated by more efficient translation of mRNA. J Appl Physiol 1999;86:1220–1225.
Short KR, Vittone JL, Bigelow ML, Proctor DN, Coenen-Schimke JM, Rys P, Nair KS. Changes in myosin heavy chain mRNA and protein expression in human skeletal muscle with age and endurance exercise training. J Appl Physiol 2005, 99:95–102
Fielding RA, Meredith CN, O’Reilly KP, Frontera WR, Cannon JG, Evans WJ. Enhanced protein breakdown after eccentric exercise in young and older men. J Appl Physiol 1991;71:674–679.
Trappe T, Williams R, Carrithers J, Raue U, Esmarck B, Kjaer M, Hickner R. Influence of age and resistance exercise on human skeletal muscle proteolysis: a microdialysis approach. J Physiol 2004, 554:803–813.
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:E677–E683.
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.
Tipton KD, Ferrando AA, Phillips SM, Doyle D, Jr., Wolfe RR. Postexercise net protein synthesis in human muscle from orally administered amino acids. Am J Physiol 1999;276:E628–E634
Tipton KD, Borsheim E, Wolf SE, Sanford AP, Wolfe RR. Acute Response of Net Muscle Protein Balance Reflects 24 H Balance Following Exercise and Amino Acid Ingestion. Am J Physiol Endocrinol Metab 2002;11:11.
Wolfe RR. Regulation of muscle protein by amino acids. J Nutr 2002;132:3219S–3224S
Tipton KD, Rasmussen BB, Miller SL, et al. Timing of amino acid-carbohydrate ingestion alters anabolic response of muscle to resistance exercise. Am J Physiol Endocrinol Metab 2001;281:E197–206.
Bales CW, Ritchie CS. Sarcopenia, weight loss, and nutritional frailty in the elderly. Annu Rev Nutr 2002;22:309–323
Onder G, Penninx BW, Balkrishnan R, et al. Relation between use of angiotensinconverting enzyme inhibitors and muscle strength and physical function in older women: an observational study. Lancet 2002;359:926–930
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Boirie, Y. Physiopathological mechanism of sarcopenia. J Nutr Health Aging 13, 717–723 (2009). https://doi.org/10.1007/s12603-009-0203-x
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DOI: https://doi.org/10.1007/s12603-009-0203-x