Int J Sports Med 2013; 34(08): 695-699
DOI: 10.1055/s-0032-1327659
Physiology & Biochemistry
© Georg Thieme Verlag KG Stuttgart · New York

Age Attenuates Leucine Oxidation after Eccentric Exercise

E. L. Kullman
1   Cleveland Clinic, Pathobiology, Cleveland, United States
,
W. W. Campbell
2   Department of Nutrition Science, Purdue University, West Lafayette, United States
,
R. K. Krishnan
3   Internal Medicine, New York University Medical Center, New York, United States
,
K. E. Yarasheski
4   Internal Medicine, Washington University School of Medicine, St. Louis, United States
,
W. J. Evans
5   GlaxoSmithKline, Muscle Metabolism Drug Performance Unit, Research Triangle Park, United States
,
J. P. Kirwan
1   Cleveland Clinic, Pathobiology, Cleveland, United States
› Author Affiliations
Further Information

Publication History



accepted after revision 17 September 2012

Publication Date:
16 January 2013 (online)

Abstract

Aging may alter protein metabolism during periods of metabolic and physiologic challenge. The purpose of this study was to assess the effects of age on whole-body amino acid turnover in response to eccentric exercise and hyperglycemia-induced hyperinsulinemia. 16 healthy men were divided into young (N=8) and older (N=8) groups. Protein metabolism was assessed using a [1-13C]-leucine isotopic tracer approach. Measures were obtained under fasted basal conditions and during 3-h hyperglycemic clamps that were performed without (control) and 48 h after eccentric exercise. Exercise reduced leucine oxidation in the younger men (P<0.05), but not in older men. Insulin sensitivity was inversely correlated with leucine oxidation (P<0.05), and was lower in older men (P<0.05). Healthy aging is associated with an impaired capacity to adjust protein oxidation in response to eccentric exercise. The decreased efficiency of protein utilization in older men may contribute to impaired maintenance, growth, and repair of body tissues with advancing age.

 
  • References

  • 1 Asp S, Daugaard JR, Kristiansen S, Kiens B, Richter EA. Eccentric exercise decreases maximal insulin action in humans: muscle and systemic effects. J Physiol 1996; 494 (Pt 3) 891-898
  • 2 Asp S, Daugaard JR, Richter EA. Eccentric exercise decreases glucose transporter GLUT4 protein in human skeletal muscle. J Physiol 1995; 482 (Pt 3) 705-712
  • 3 American Diabetes Association . Screening for type 2 diabetes (Position Statement). Diabetes Care 1999; 22: S20-S23
  • 4 Burd NA, Wall BT, van Loon LJ. The curious case of anabolic resistance: old wives’ tales or new fables?. J Appl Physiol 2012; 112: 1233-1235
  • 5 Coon PJ, Rogus EM, Drinkwater D, Muller DC, Goldberg AP. Role of body fat distribution in the decline in insulin sensitivity and glucose tolerance with age. J Clin Endocrinol Metab 1992; 75: 1125-1132
  • 6 Cuthbertson D, Smith K, Babraj J, Leese G, Waddell T, Atherton P, Wackerhage H, Taylor PM, Rennie MJ. Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. FASEB J 2005; 19: 422-424
  • 7 Del Aguila LF, Krishnan RK, Ulbrecht JS, Farrell PA, Correll PH, Lang CH, Zierath JR, Kirwan JP. Muscle damage impairs insulin stimulation of IRS-1, PI 3-kinase, and Akt-kinase in human skeletal muscle. Am J Physiol 2000; 279: E206-E212
  • 8 Duggleby SL, Waterlow JC. The end-product method of measuring whole-body protein turnover: a review of published results and a comparison with those obtained by leucine infusion. Br J Nutr 2005; 94: 141-153
  • 9 Evans WJ, Meredith CN, Cannon JG, Dinarello CA, Frontera WR, Hughes VA, Jones BH, Knuttgen HG. Metabolic changes following eccentric exercise in trained and untrained men. J Appl Physiol 1986; 61: 1864-1868
  • 10 Fiatarone MA, O’Neill EF, Ryan ND, Clements KM, Solares GR, Nelson ME, Roberts SB, Kehayias JJ, Lipsitz LA, Evans WJ. Exercise training and nutritional supplementation for physical frailty in very elderly people. N Engl J Med 1994; 330: 1769-1775
  • 11 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
  • 12 Fujita S, Glynn EL, Timmerman KL, Rasmussen BB, Volpi E. Supraphysiological hyperinsulinaemia is necessary to stimulate skeletal muscle protein anabolism in older adults: evidence of a true age-related insulin resistance of muscle protein metabolism. Diabetologia 2009; 52: 1889-1898
  • 13 Harriss DJ, Atkinson G. Update – ethical standards in sport and exercise science research. Int J Sports Med 2011; 32: 819-821
  • 14 Hotamisligil GS. Mechanisms of TNF-alpha-induced insulin resistance. Exp Clin Endocrinol Diabetes 1999; 107: 119-125
  • 15 Katsanos CS, Kobayashi H, Sheffield-Moore M, Aarsland A, Wolfe RR. 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
  • 16 King DS, Feltmeyer TL, Baldus PJ, Sharp RL, Nespor J. Effects of eccentric exercise on insulin secretion and action in humans. J Appl Physiol 1993; 75: 2151-2156
  • 17 Kirwan JP, Hickner RC, Yarasheski KE, Kohrt WM, Wiethop BV, Holloszy JO. Eccentric exercise induces transient insulin resistance in healthy individuals. J Appl Physiol 1992; 72: 2197-2202
  • 18 Kirwan JP, Krishnan RK, Weaver JA, Del Aguila LF, Evans WJ. Human aging is associated with altered TNF-alpha production during hyperglycemia and hyperinsulinemia. Am J Physiol 2001; 281: E1137-E1143
  • 19 Kohrt WM, Kirwan JP, Staten MA, Bourey RE, King DS, Holloszy JO. Insulin resistance in aging is related to abdominal obesity. Diabetes 1993; 42: 273-281
  • 20 Krishnan RK, Evans WJ, Kirwan JP. Glucose clearance is delayed after hyperglycemia in healthy elderly men. J Nutr 2003; 133: 2363-2366
  • 21 Krishnan RK, Evans WJ, Kirwan JP. Impaired substrate oxidation in healthy elderly men after eccentric exercise. J Appl Physiol 2003; 94: 716-723
  • 22 Krishnan RK, Hernandez JM, Williamson DL, O'Gorman DJ, Evans WJ, Kirwan JP. Age-related differences in the pancreatic beta-cell response to hyperglycemia after eccentric exercise. Am J Physiol 1998; 275: E463-E470
  • 23 Liao P, Zhou J, Ji LL, Zhang Y. Eccentric contraction induces inflammatory responses in rat skeletal muscle: role of tumor necrosis factor-alpha. Am J Physiol 2010; 298: R599-R607
  • 24 Manfredi TG, Fielding RA, O'Reilly KP, Meredith CN, Lee HY, Evans WJ. Plasma creatine kinase activity and exercise-induced muscle damage in older men. Med Sci Sports Exerc 1991; 23: 1028-1034
  • 25 Matthews DE, Motil KJ, Rohrbaugh DK, Burke JF, Young VR, Bier DM. Measurement of leucine metabolism in man from a primed, continuous infusion of L-[1-3C]leucine. Am J Physiol 1980; 238: E473-E479
  • 26 Matthews DE, Schwarz HP, Yang RD, Motil KJ, Young VR, Bier DM. Relationship of plasma leucine and alpha-ketoisocaproate during a L-[1-13C]leucine infusion in man: a method for measuring human intracellular leucine tracer enrichment. Metabolism 1982; 31: 1105-1112
  • 27 Maury E, Brichard SM. Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Mol Cell Endocrinol 2010; 314: 1-16
  • 28 Miles MP, Depner CM, Kirwan RD, Frederickson SJ. Influence of macronutrient intake and anthropometric characteristics on plasma insulin after eccentric exercise. Metabolism 2010; 59: 1456-1464
  • 29 Narici MV, Maffulli N. Sarcopenia: characteristics, mechanisms and functional significance. Br Med Bull 2010; 95: 139-159
  • 30 Peake J, Nosaka K, Suzuki K. Characterization of inflammatory responses to eccentric exercise in humans. Exerc Immunol Rev 2005; 11: 64-85
  • 31 Pereira S, Marliss EB, Morais JA, Chevalier S, Gougeon R. Insulin resistance of protein metabolism in type 2 diabetes. Diabetes 2008; 57: 56-63
  • 32 Phillips SM, Tipton KD, Aarsland A, Wolf SE, Wolfe RR. Mixed muscle protein synthesis and breakdown after resistance exercise in humans. Am J Physiol 1997; 273: E99-E107
  • 33 Rasmussen BB, Fujita S, Wolfe RR, Mittendorfer B, Roy M, Rowe VL, Volpi E. Insulin resistance of muscle protein metabolism in aging. FASEB J 2006; 20: 768-769
  • 34 Raue U, Slivka D, Minchev K, Trappe S. Improvements in whole muscle and myocellular function are limited with high-intensity resistance training in octogenarian women. J Appl Physiol 2009; 106: 1611-1617
  • 35 Reeds DN, Cade WT, Patterson BW, Powderly WG, Klein S, Yarasheski KE. Whole-body proteolysis rate is elevated in HIV-associated insulin resistance. Diabetes 2006; 55: 2849-2855
  • 36 Schwarz HP, Karl IE, Bier DM. The alpha-keto acids of branched-chain amino acids: simplified derivatization for physiological samples and complete separation as quinoxalinols by packed column gas chromatography. Anal Biochem 1980; 108: 360-366
  • 37 Slivka D, Raue U, Hollon C, Minchev K, Trappe S. Single muscle fiber adaptations to resistance training in old (>80 yr) men: evidence for limited skeletal muscle plasticity. Am J Physiol 2008; 295: R273-R280
  • 38 Tessari P, Cecchet D, Cosma A, Puricelli L, Milloni R, Vedovato M, Tiengo A. Insulin resistance of amino acid and protein metabolism in type 2 diabetes. Clin Nutr 2011; 30: 267-272
  • 39 Toth MJ, Tchernof A, Rosen CJ, Matthews DE, Poehlman ET. Regulation of protein metabolism in middle-aged, premenopausal women: roles of adiposity and estradiol. J Clin Endocrinol Metab 2000; 85: 1382-1387
  • 40 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
  • 41 Welle S, Thornton C, Statt M, McHenry B. Postprandial myofibrillar and whole body protein synthesis in young and old human subjects. Am J Physiol 1994; 267: E599-E604
  • 42 Yarasheski KE, Smith SR, Powderly WG. Reducing plasma HIV RNA improves muscle amino acid metabolism. Am J Physiol 2005; 288: E278-E284
  • 43 Yarasheski KE, Zachwieja JJ, Gischler J, Crowley J, Horgan MM, Powderly WG. Increased plasma gln and Leu Ra and inappropriately low muscle protein synthesis rate in AIDS wasting. Am J Physiol 1998; 275: E577-E583