Cited by 168Muscle metabolism and nutritionMuscle Physiology and DisordersNutrition and Health in Aging

Differences in Muscle Protein Synthesis and Anabolic Signaling in the Postabsorptive State and in Response to Food in 65–80 Year Old Men and Women

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Smith, Gordon I., Atherton, Philip, Villareal, Dennis T., Frimel, Tiffany N., Rankin, Debbie, Rennie, Michael J., Mittendorfer, Bettina·2008·PLoS ONE

Abstract

Women have less muscle than men but lose it more slowly during aging. To discover potential underlying mechanism(s) for this we evaluated the muscle protein synthesis process in postabsorptive conditions and during feeding in twenty-nine 65-80 year old men (n = 13) and women (n = 16). We discovered that the basal concentration of phosphorylated eEF2(Thr56) was approximately 40% less (P<0.05) and the basal rate of MPS was approximately 30% greater (P = 0.02) in women than in men; the basal concentrations of muscle phosphorylated Akt(Thr308), p70s6k(Thr389), eIF4E(Ser209), and eIF4E-BP1(Thr37/46) were not different between the sexes. Feeding increased (P<0.05) Akt(Thr308) and p70s6k(Thr389) phosphorylation to the same extent in men and women but increased (P<0.05) the phosphorylation of eIF4E(Ser209) and eIF4E-BP1(Thr37/46) in men only. Accordingly, feeding increased MPS in men (P<0.01) but not in women. The postabsorptive muscle mRNA concentrations for myoD and myostatin were not different between sexes; feeding doubled myoD mRNA (P<0.05) and halved that of myostatin (P<0.05) in both sexes. Thus, there is sexual dimorphism in MPS and its control in older adults; a greater basal rate of MPS, operating over most of the day may partially explain the slower loss of muscle in older women.

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  1. [1]Horowitz JF Coppack SW Klein S 2001 Whole-body and adipose tissue glucose metabolism in response to short-term fasting in lean and obese women. Am J Clin Nutr 73 517 522 11237926
  2. [2]Zierler K 1999 Whole body glucose metabolism. Am J Physiol 276 E409 426 10070005
  3. [3]Kraegen EW Jenkins AB Storlien LH Chisholm DJ 1990 Tracer studies of in vivo insulin action and glucose metabolism in individual peripheral tissues. Horm Metab Res Suppl 24 41 48 2272625
  4. [4]Radegran G Blomstrand E Saltin B 1999 Peak muscle perfusion and oxygen uptake in humans: importance of precise estimates of muscle mass. J Appl Physiol 87 2375 2380 10601192
  5. [5]Forbes GB Reina JC 1970 Adult lean body mass declines with age: some longitudinal observations. Metabolism 19 653 663 5459997
  6. [6]Mingrone G Marino S DeGaetano A Capristo E Heymsfield SB 2001 Different limit to the body's ability of increasing fat-free mass. Metabolism 50 1004 1007 11555829
  7. [7]Gallagher D Ruts E Visser M Heshka S Baumgartner RN 2000 Weight stability masks sarcopenia in elderly men and women. Am J Physiol Endocrinol Metab 279 E366 375 10913037
  8. [8]Hughes VA Frontera WR Roubenoff R Evans WJ Singh MA 2002 Longitudinal changes in body composition in older men and women: role of body weight change and physical activity. Am J Clin Nutr 76 473 481 12145025
  9. [9]Zamboni M Zoico E Scartezzini T Mazzali G Tosoni P 2003 Body composition changes in stable-weight elderly subjects: the effect of sex. Aging Clin Exp Res 15 321 327 14661824
  10. [10]Bhasin S Woodhouse L Storer TW 2001 Proof of the effect of testosterone on skeletal muscle. J Endocrinol 170 27 38 11431134
  11. [11]Buresova M Gutmann E 1971 Effect of testosterone on protein synthesis and contractility of the levator ani muscle of the rat. J Endocrinol 50 643 651 5564408
  12. [12]Grigsby JS Bergen WG Merkel RA 1976 The effect of testosterone on skeletal muscle development and protein synthesis in rabbits. Growth 40 303 316 1010388
  13. [13]Rooyackers OE Nair KS 1997 Hormonal regulation of human muscle protein metabolism. Annu Rev Nutr 17 457 485 9240936
  14. [14]Umpleby AM Russell-Jones DL 1996 The hormonal control of protein metabolism. Baillieres Clin Endocrinol Metab 10 551 570 9022951
  15. [16]Griggs RC Kingston W Jozefowicz RF Herr BE Forbes G 1989 Effect of testosterone on muscle mass and muscle protein synthesis. J Appl Physiol 66 498 503 2917954
  16. [17]Toth MJ Poehlman ET Matthews DE Tchernof A MacCoss MJ 2001 Effects of estradiol and progesterone on body composition, protein synthesis, and lipoprotein lipase in rats. Am J Physiol Endocrinol Metab 280 E496 501 11171605
  17. [18]McCormick KM Burns KL Piccone CM Gosselin LE Brazeau GA 2004 Effects of ovariectomy and estrogen on skeletal muscle function in growing rats. J Muscle Res Cell Motil 25 21 27 15160484
  18. [19]Piccone CM Brazeau GA McCormick KM 2005 Effect of oestrogen on myofibre size and myosin expression in growing rats. Exp Physiol 90 87 93 15466459
  19. [20]Fujita S Rasmussen BB Bell JA Cadenas JG Volpi E 2007 Basal muscle intracellular amino acid kinetics in women and men. Am J Physiol Endocrinol Metab 292 E77 83 16896165 PMC2804963
  20. [22]Jahn LA Barrett EJ Genco ML Wei L Spraggins TA 1999 Tissue composition affects measures of postabsorptive human skeletal muscle metabolism: comparison across genders. J Clin Endocrinol Metab 84 1007 1010 10084587
  21. [23]Vary TC Jefferson LS Kimball SR 1999 Amino acid-induced stimulation of translation initiation in rat skeletal muscle. Am J Physiol 277 E1077 1086 10600798
  22. [24]Millward DJ Garlick PJ James WP Nnanyelugo DO Ryatt JS 1973 Relationship between protein synthesis and RNA content in skeletal muscle. Nature 241 204 205 4700888
  23. [26]Frost RA Lang CH 2007 Protein kinase B/Akt: a nexus of growth factor and cytokine signaling in determining muscle mass. J Appl Physiol 103 378 387 17332274
  24. [27]Lee SJ McPherron AC 2001 Regulation of myostatin activity and muscle growth. Proc Natl Acad Sci U S A 98 9306 9311 11459935 PMC55416
  25. [30]Toth MJ Matthews DE Tracy RP Previs MJ 2005 Age-related differences in skeletal muscle protein synthesis: relation to markers of immune activation. Am J Physiol Endocrinol Metab 288 E883 891 15613683
  26. [31]Schaap LA Pluijm SM Deeg DJ Visser M 2006 Inflammatory markers and loss of muscle mass (sarcopenia) and strength. Am J Med 119 526 e529 517 16750969
  27. [32]Visser M Pahor M Taaffe DR Goodpaster BH Simonsick EM 2002 Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the Health ABC Study. J Gerontol A Biol Sci Med Sci 57 M326 332 11983728
  28. [33]Roubenoff R 2003 Catabolism of aging: is it an inflammatory process? Curr Opin Clin Nutr Metab Care 6 295 299 12690262
  29. [34]Dietrichson P Coakley J Smith PE Griffiths RD Helliwell TR 1987 Conchotome and needle percutaneous biopsy of skeletal muscle. J Neurol Neurosurg Psychiatry 50 1461 1467 3694206 PMC1032558
  30. [35]Patterson BW Zhang XJ Chen Y Klein S Wolfe RR 1997 Measurement of very low stable isotope enrichments by gas chromatography/mass spectrometry: application to measurement of muscle protein synthesis. Metabolism 46 943 948 9258279
  31. [36]Livak KJ Schmittgen TD 2001 Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25 402 408 11846609
  32. [37]Watt PW Lindsay Y Scrimgeour CM Chien PA Gibson JN 1991 Isolation of aminoacyl-tRNA and its labeling with stable-isotope tracers: Use in studies of human tissue protein synthesis. Proc Natl Acad Sci U S A 88 5892 5896 2062866 PMC51984
  33. [38]Mittendorfer B Andersen JL Plomgaard P Saltin B Babraj JA 2005 Protein synthesis rates in human muscles: neither anatomical location nor fibre-type composition are major determinants. J Physiol 563 203 211 15611031 PMC1665563
  34. [40]McMahon CD Popovic L Jeanplong F Oldham JM Kirk SP 2003 Sexual dimorphism is associated with decreased expression of processed myostatin in males. Am J Physiol Endocrinol Metab 284 E377 381 12388123
  35. [41]Brodsky IG Balagopal P Nair KS 1996 Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men–a clinical research center study. J Clin Endocrinol Metab 81 3469 3475 8855787
  36. [42]Urban RJ Bodenburg YH Gilkison C Foxworth J Coggan AR 1995 Testosterone administration to elderly men increases skeletal muscle strength and protein synthesis. Am J Physiol 269 E820 826 7491931
  37. [43]Ferrando AA Sheffield-Moore M Paddon-Jones D Wolfe RR Urban RJ 2003 Differential anabolic effects of testosterone and amino acid feeding in older men. J Clin Endocrinol Metab 88 358 362 12519877
  38. [45]Volpi E Sheffield-Moore M Rasmussen BB Wolfe RR 2001 Basal muscle amino acid kinetics and protein synthesis in healthy young and older men. JAMA 286 1206 1212 11559266 PMC3183815
  39. [49]Crozier SJ Kimball SR Emmert SW Anthony JC Jefferson LS 2005 Oral leucine administration stimulates protein synthesis in rat skeletal muscle. J Nutr 135 376 382 15735066
  40. [50]Garlick PJ 2005 The role of leucine in the regulation of protein metabolism. J Nutr 135 1553S 1556S 15930468
  41. [52]Pitkanen HT Oja SS Kemppainen K Seppa JM Mero AA 2003 Serum amino acid concentrations in aging men and women. Amino Acids 24 413 421 12768504
  42. [53]Long CL Birkhahn RH Geiger JW Blakemore WS 1981 Contribution of skeletal muscle protein in elevated rates of whole body protein catabolism in trauma patients. Am J Clin Nutr 34 1087 1093 7234737
  43. [54]Morais JA Gougeon R Pencharz PB Jones PJ Ross R 1997 Whole-body protein turnover in the healthy elderly. Am J Clin Nutr 66 880 889 9322564
  44. [55]Partridge T 2000 The current status of myoblast transfer. Neurol Sci 21 S939 942 11382193
  45. [56]Lind L Fugmann A Millgard J Berne C Lithell H 2002 Insulin-mediated vasodilatation, but not glucose uptake or endothelium-mediated vasodilatation, is enhanced in young females compared with males. Clin Sci (Lond) 102 241 246 11834144
  46. [57]Celermajer DS Sorensen KE Spiegelhalter DJ Georgakopoulos D Robinson 1994 Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women. J Am Coll Cardiol 24 471 476 8034885
  47. [58]Sarabi M Millgard J Lind L 1999 Effects of age, gender and metabolic factors on endothelium-dependent vasodilation: a population-based study. J Intern Med 246 265 274 10475994
  48. [59]Jensen-Urstad K Johansson J 2001 Gender difference in age-related changes in vascular function. J Intern Med 250 29 36 11454139
  49. [60]Clark MG Rattigan S Barrett EJ 2006 Nutritive blood flow as an essential element supporting muscle anabolism. Curr Opin Clin Nutr Metab Care 9 185 189 16607114
  50. [61]Sheffield-Moore M Urban RJ Wolf SE Jiang J Catlin DH 1999 Short-term oxandrolone administration stimulates net muscle protein synthesis in young men. J Clin Endocrinol Metab 84 2705 2711 10443664
  51. [62]Rousset S Patureau Mirand P Brandolini M Martin JF Boirie Y 2003 Daily protein intakes and eating patterns in young and elderly French. Br J Nutr 90 1107 1115 14641970
  52. [63]Cid-Ruzafa J Caulfield LE Barron Y West SK 1999 Nutrient intakes and adequacy among an older population on the eastern shore of Maryland: the Salisbury Eye Evaluation. J Am Diet Assoc 99 564 571 10333778
  53. [64]Ledikwe JH Smiciklas-Wright H Mitchell DC Miller CK Jensen GL 2004 Dietary patterns of rural older adults are associated with weight and nutritional status. J Am Geriatr Soc 52 589 595 15066076
  54. [65]Adibi SA Mercer DW 1973 Protein digestion in human intestine as reflected in luminal, mucosal, and plasma amino acid concentrations after meals. J Clin Invest 52 1586 1594 4718954 PMC302429
  55. [66]Bergstrom J Furst P Vinnars E 1990 Effect of a test meal, without and with protein, on muscle and plasma free amino acids. Clin Sci (Lond) 79 331 337 2171853
  56. [67]Remond D Machebeuf M Yven C Buffiere C Mioche L 2007 Postprandial whole-body protein metabolism after a meat meal is influenced by chewing efficiency in elderly subjects. Am J Clin Nutr 85 1286 1292 17490964
  57. [68]Tsai PJ Wu WH Huang PC 2000 Circadian variations in plasma neutral and basic amino acid concentrations in young men on an ordinary Taiwanese diet. J Formos Med Assoc 99 151 157 10770030
  58. [69]Bohe J Low JF Wolfe RR Rennie MJ 2001 Latency and duration of stimulation of human muscle protein synthesis during continuous infusion of amino acids. J Physiol 532 575 579 11306673 PMC2278544
  59. [72]Chevalier S Marliss EB Morais JA Lamarche M Gougeon R 2005 The influence of sex on the protein anabolic response to insulin. Metabolism 54 1529 1535 16253644

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Authors
Smith, G. I., Atherton, P., Villareal, D. T., Frimel, T. N., Rankin, D., Rennie, M. J., & Mittendorfer, B.
Affiliations
  • Washington University in St. Louis (US)
  • University of Nottingham (GB)
Corresponding author
Mittendorfer, Bettina
Venue
PLoS ONE
Published
2008-03-26
Volume
3
Issue
3
Pages
e1875
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2169296372
Cited by
168
References
12
Citations by year
2026: 6 · 2025: 6 · 2024: 10 · 2023: 11 · 2022: 6 · 2021: 15 · 2020: 11 · 2019: 7 · 2018: 11 · 2017: 9 · 2016: 10 · 2015: 10 · 2014: 5 · 2013: 5 · 2012: 13
FWCI
4.82
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Research Councils UK
  • European Commission
  • University of Nottingham
  • National Institutes of Health (5p41rr000954-34, 7r01ag025501-06, DK56341, AR 49869, RR-00954)
  • Directorate for Biological Sciences
  • Biotechnology and Biological Sciences Research Council (BB/C516779/1, BB/XX510697/1)
  • National Institute on Aging (R01-AG025501, AG-025501)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK56341, P30DK056341)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR049869, AR49869)
  • National Center for Research Resources (P41-RR000954, RR 00954, RR.00036, M01RR000036)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
Keywords
muscle protein synthesis, sexual dimorphism, aging, postabsorptive state, feeding response, anabolic signaling, eEF2 phosphorylation, Akt phosphorylation, p70S6K, eIF4E, myostatin, MyoD, sarcopenia, older adults
MeSH terms
Aged, Aged, 80 and over, Female, Humans, Intestinal Absorption, Male, Muscle Proteins, Phosphorylation, Signal Transduction, Ribosomal Protein S6 Kinases, Eukaryotic Initiation Factor-4E, Proto-Oncogene Proteins c-akt

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