Advertisement

The journal of nutrition, health & aging

, Volume 15, Issue 10, pp 890–895 | Cite as

Discovering pathways of sarcopenia in older adults: A role for insulin resistance on mitochondria dysfunction

  • Angela Marie Abbatecola
  • G. Paolisso
  • P. Fattoretti
  • W. J. Evans
  • V. Fiore
  • L. Dicioccio
  • F. Lattanzio
Discovering Pathways of Sarcopenia in Older Adults

Abstract

The precise cause of sarcopenia, skeletal muscle loss and strength, in older persons is unknown. However, there is a strong evidence for muscle loss due to insulin resistance as well as mitochondrial dysfunction over aging. Considering that epidemiological studies have underlined that insulin resistance may have a specific role on skeletal muscle fibre atrophy and mitochondrial dysfunction has also been extensively shown to have a pivotal role on muscle loss in older persons, a combined pathway may not be ruled out. Considering that there is growing evidence for an insulin-related pathway on mitochondrial signaling, we hypothesize that a high degree of insulin resistance will be associated with the development of sarcopenia through specific alterations on mitochondrial functioning. This paper will highlight recent reviews regarding the link between skeletal muscle mitochondrial dysfunction and insulin resistance. We will specifically emphasize possible steps involved in sarcopenia over aging, including potential biomolecular mechanisms of insulin resistance on mitochondrial functioning.

Key words

Insulin resistance sarcopenia aging mitochondria 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Abbatecola AM, Ferrucci L, Ceda G, Russo CR, Lauretani F, Bandinelli S, Barbieri M, Valenti G, Paolisso G. (2005) Insulin resistance and muscle strength in older persons. J Gerontol A Biol Sci Med Sci;60(10):1278–1282.PubMedCrossRefGoogle Scholar
  2. 2.
    Park SW, Goodpaster BH, Lee JS, Kuller LH, Boudreau R, de Rekeneire N, Harris TB, Kritchevsky S, Tylavsky FA, Nevitt M, Cho YW, Newman AB; Health, Aging, and Body Composition Study (2009) Excessive loss of skeletal muscle mass in older adults with type 2 diabetes. Diabetes Care;32(11):1993–1997PubMedCrossRefGoogle Scholar
  3. 3.
    Wang M, Wang XC, Zhang ZY, Mou B, Hu RM. (2010) Impaired mitochondrial oxidative phosphorylation in multiple insulin-sensitive tissues of humans with type 2 diabetes mellitus. J Int Med Res;38(3):769–781.PubMedGoogle Scholar
  4. 4.
    Ritov VB, Menshikova EV, Azuma K, Wood R, Toledo FG, Goodpaster BH, Ruderman NB, Kelley DE. (2010) Deficiency of electron transport chain in human skeletal muscle mitochondria in type 2 diabetes mellitus and obesity. Am J Physiol Endocrinol Metab;298(1):E49–E58PubMedCrossRefGoogle Scholar
  5. 5.
    Lennmarken C, Bergman T, Larsson J, Larsson L-E. (1985) Skeletal muscle function in man: force, relaxation rate, endurance and contraction time-dependence on sex and age. Clin Physiol;5:243–255.PubMedGoogle Scholar
  6. 6.
    Jubrias SA, Odderson IR, Esselman PC, Conley KE. (1997) Decline in isokinetic force with age: muscle cross-sectional area and specific force. Arch Eur J Physiol;434:246–253CrossRefGoogle Scholar
  7. 7.
    Wolfson L, Judge J, Whipple R, King M. (1995) Strength is a major factor in balance, gait, and the occurrence of falls. J Gerontol;50A:64–68.Google Scholar
  8. 8.
    Evans WJ, Cyr-Campbell D. (1997) Nutrition, exercise, and healthy aging. J Am Diet Assoc;97(6):632–638.PubMedCrossRefGoogle Scholar
  9. 9.
    Mokdad AH, Ford ES, Bowman BA, et al. (2003) Prevalence of obesity, diabetes and obesity-related risk-factors. JAMA; 289:76–79.PubMedCrossRefGoogle Scholar
  10. 10.
    Short KR, Bigelow ML, Kahl J, Singh R, Coenen-Schimke J, Raghavakaimal S, Nair KS (2005) Decline in skeletal muscle mitochondrial function with aging in humans. Proc Nat Acad Sci USA;102(15):5618–5623.PubMedCrossRefGoogle Scholar
  11. 11.
    Song XM, Ryder JW, Kawano Y, Chibalin AV, Krook A, Zierath JR (1999) Muscle fiber type specificity in insulin signal transduction. Am J Physiol;277(6 Pt 2):R1690–1696.PubMedGoogle Scholar
  12. 12.
    Lexell J, Henriksson-Larsen K, Wilblad B, Siostrom M. (1983) Distribution of aging studied in whole muscle cross-sections. Muscle Nerve; 6:588–595.PubMedCrossRefGoogle Scholar
  13. 13.
    Madsen OR, Lauridsen UB, Hartkopp A, Sorensen OH (1997) Muscle strength and soft tissue composition as measured by dual energy x-ray absorptiometry in women aged 18–87 years. Eur J Appl Physiol Occup Physiol;76:239–245.CrossRefGoogle Scholar
  14. 14.
    Cesari M, Leeuwenburgh C, Lauretani F, Onder G, Bandinelli S, Maraldi C, Guralnik JM, Pahor M, Ferrucci L. (2006) Frailty syndrome and skeletal muscle: results from the Invecchiare in Chianti study. Am J Clin Nutr;83(5):1142–1148.PubMedGoogle Scholar
  15. 15.
    Rolland Y, Czerwinski S, Abellan Van Kan G, Morley JE, Cesari M, Onder G, Woo J, Baumgartner R, Pillard F, Boirie Y, Chumlea WM, Vellas B. (2008) Sarcopenia: its assessment, etiology, pathogenesis, consequences and future perspectives. J Nutr Health Aging;12(7):433–450PubMedCrossRefGoogle Scholar
  16. 16.
    Boncompagni S, d’Amelio L, Fulle S, Fanò G, Protasi F (2006) Progressive disorganization of the excitation-contraction coupling apparatus in aging human skeletal muscle as revealed by electron microscopy: a possible role in the decline of muscle performance. J Gerontol A Biol Sci Med Sci;61(10):995–1008.PubMedCrossRefGoogle Scholar
  17. 17.
    Aiken J, Bua E, Cao Z, Lopez M, Wanagat J, et al. (2002) Mitochondrial DNA deletion mutations and sarcopenia. Ann N Y Acad Sci;959:412–423.PubMedCrossRefGoogle Scholar
  18. 18.
    Bua E, Johnson J, Herbst A, Delong B, McKenzie D, et al. (2006) Mitochondrial DNA-deletion mutations accumulate intracellularly to detrimental levels in aged human skeletal muscle fibers. Am J Hum Genet;79:469–480.PubMedCrossRefGoogle Scholar
  19. 19.
    Bua EA, McKiernan SH, Wanagat J, McKenzie D, Aiken JM. (2002) Mitochondrial abnormalities are more frequent in muscles undergoing sarcopenia. J Appl Physiol;92:2617–2624.PubMedGoogle Scholar
  20. 20.
    Wanagat J, Cao Z, Pathare P, Aiken JM. (2001) Mitochondrial DNA deletion mutations colocalize with segmental electron transport system abnormalities, muscle fiber atrophy, fiber splitting, and oxidative damage in sarcopenia. Faseb J;15:322–332.PubMedCrossRefGoogle Scholar
  21. 21.
    Hsieh RH, Hou JH, Hsu HS, Wei YH. (1994) Age-dependent respiratory function decline and DNA deletions in human muscle mitochondria. Biochem Mol Biol Int;32:1009–1022PubMedGoogle Scholar
  22. 22.
    Trounce I, Byrne E, Marzuki S. (1989) Decline in skeletal muscle mitochondrial respiratory chain function: possible factor in ageing. Lancet;1:637–639.PubMedCrossRefGoogle Scholar
  23. 23.
    Barrientos A, Casademont J, Rotig A, Miro O, Urbano-Marquez A, et al. (1996) Absence of relationship between the level of electron transport chain activities and aging in human skeletal muscle. Biochem Biophys Res Commun;229:536–539.PubMedCrossRefGoogle Scholar
  24. 24.
    Parise G, Kaczor J, Mahoney J, Phillips S, Tarnopolsky M (2004). Oxidative stress and the mitochondrial theory of aging in human skeletal muscle. Experimental Gerontology;39:1391–1400.CrossRefGoogle Scholar
  25. 25.
    Castillo EM, Goodman-Gruen D, Kritz-Silverstein D, Morton DJ, Wingard DL, Barrett-Connor E. (2003) Sarcopenia in elderly men and women: the Rancho Bernardo study. Am J Prev Med;25(3):226–231.PubMedCrossRefGoogle Scholar
  26. 26.
    Hoeks J, van Herpen NA, Mensink M, Moonen-Kornips E, van Beurden D, Hesselink MK, Schrauwen P. (2010) Prolonged fasting identifies skeletal muscle mitochondrial dysfunction as consequence rather than cause of human insulin resistance. Diabetes;59(9):2117–21PubMedCrossRefGoogle Scholar
  27. 27.
    Barazzoni R, Short KR, Nair KS. (2000) Effects of aging on mitochondrial DNA copy number and cytochrome c oxidase gene expression in rat skeletal muscle, liver and heart. J Biol Chem;275:3343–3347.PubMedCrossRefGoogle Scholar
  28. 28.
    Huang X, Eriksson K-F, Vaag A, et al. (1999) Insulin-regulated mitochondrial gene expression is associatedwith glucose flux in human skeletal muscle. Diabetes;48:1508–1514.PubMedCrossRefGoogle Scholar
  29. 29.
    Huang X, Eriksson K-F, Vaag A, et al. (1999) Insulin-regulated mitochondrial gene expression is associated with glucose flux in human skeletal muscle. Diabetes; 48:1508–1514.PubMedCrossRefGoogle Scholar
  30. 30.
    Stump CS, Short KR, Bigelow ML, et al. (2003) Effect of insulin on human skeletal muscle mitochondrial ATP production, protein synthesis, and mRNA transcripts. Proc Natl Acad Sci USA; 100:7996–8001.PubMedCrossRefGoogle Scholar
  31. 31.
    Boirie Y, Short KR, Ahlman B, et al. (2001) Tissue-specific regulation of mitochondrial and cytoplasmic protein synthesis rates by insulin. Diabetes;50:2652–2658.PubMedCrossRefGoogle Scholar
  32. 32.
    Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, DiPietro L, Cline GW, Shulman GI. (2003) Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science;300(5622):1140–1142.PubMedCrossRefGoogle Scholar
  33. 33.
    Mootha V, Lindgren CM, Eriksson KF et al. (2003) PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat. Genet. 34, 267–273PubMedCrossRefGoogle Scholar
  34. 34.
    Patti M, Butte AJ, Crunkhorn S et al. (2003) Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1. Proc. Natl. Acad. Sci. U. S. A. 100, 8466–8471)PubMedCrossRefGoogle Scholar
  35. 35.
    Ritov VB, Menshikova EV, He J, Ferrell RE, Goodpaster BH, Kelley DE (2005) Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes. Diabetes 54, 8–14 12).PubMedCrossRefGoogle Scholar
  36. 36.
    Barletta, A., and Liverini, G. (2003) Effect of high-fat feeding on metabolic efficiency and mitochondrial oxidative capacity in adult rats. Br. J. Nutr. 90, 953–960PubMedCrossRefGoogle Scholar
  37. 37.
    Bonnard C, Durand A, Peyrol S, Chanseaume E, Chauvin MA, Morio B, Vidal H, Rieusset J. (2008) Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice. J Clin Invest;118(2):789–800.PubMedGoogle Scholar
  38. 38.
    Hancock, C. R., Han, D. H., Chen, M., Terada, S., Yasuda, T., Wright, D. C, Holloszy, J. O. (2008) High-fat diets cause insulin resistance despite an increase in muscle mitochondria. Proc. Natl. Acad. Sci. USA 105, 7815–7820.PubMedCrossRefGoogle Scholar
  39. 39.
    Short KR, Vittone JL, Bigelow ML, Proctor DN, Rizza RA, Coenen-Schimke JM, Nair KS (2003) Impact of aerobic exercise training on age-related changes in insulin sensitivity and muscle oxidative capacity. Diabetes;52(8):1888–1896PubMedCrossRefGoogle Scholar
  40. 40.
    Dumas JF, Simard G, Flamment M, Ducluzeau PH, Ritz P (2009) Is skeletal muscle mitochondrial dysfunction a cause or an indirect consequence of insulin resistance in humans? Diabetes Metab;35(3):159–167PubMedCrossRefGoogle Scholar
  41. 41.
    Anderson EJ, Lustig ME, Boyle KE, et al. (2009) Mitochondrial H2O2 emission and cellular redox state link excess fat intake insulin reisistance in both rodents and humans, J Clin Invest 119: 573–581PubMedCrossRefGoogle Scholar
  42. 42.
    Han DH, Hancock CR, Jung SR, Higashida K, Kim SH, Holloszy JO. (2011) Deficiency of the mitochondrial electron transport chain in muscle does not cause insulin resistance. PLoS One;6(5):e19739.Google Scholar
  43. 43.
    Morino K, Petersen KF, Shulman GI (2006) Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction. Diabetes 55: S9–S15PubMedCrossRefGoogle Scholar
  44. 44.
    Chattopadhyay M, Guhathakurta I, Behera P, Ranjan KR, Khanna M, Mukhopadhyay S, Chakrabarti S. (2011) Mitochondrial bioenergetics is not impaired in nonobese subjects with type 2 diabetes mellitus. Metabolism.Google Scholar
  45. 45.
    Goodpaster BH, Thaete FL, Simoneau JA, Kelley DE. (1997) Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat. Diabetes; 46: 1579–1585.PubMedCrossRefGoogle Scholar
  46. 46.
    Torriani M, Hadigan C, Jensen ME, Grinspoon S. (2003) Psoas muscle attenuation measurement with computed tomography indicates intramuscular fat accumulation in patients with HIV-lipodystrophy syndrome. J Appl Physiol;95: 1005–1101PubMedGoogle Scholar
  47. 47.
    Goodpaster BH, Carlson CL, Visser M, Kelley DH, Scherzinger A, Harris TB, Stamm E, Newman AB. (2001) Attenuation of skeletal muscle and strength in the elderly. The Health ABC study. J Appl Phsiol;90: 2157–2165Google Scholar
  48. 48.
    Abbatecola AM, Chiodini P, Gallo C, Lakatta E, Sutton-Tyrrell K, Tylavsky FA, Goodpaster B, de Rekeneire N, Schwartz AV, Paolisso G, Harris T; for the Health ABC study (2011) Pulse wave velocity is associated with muscle mass decline: Health ABC study. Age (Dordr).Google Scholar
  49. 49.
    Lowell BB, Shulman GI. Mitochondrial dysfunction and type 2 diabetes. Science. 2005;307(5708):384–387.PubMedCrossRefGoogle Scholar
  50. 50.
    Riedl I, Yoshioka M, St-Amand J. Concomitant modulation of transcripts related to fiber type determination and energy metabolism in skeletal muscle of female ovariectomized mice by estradiol injection. J Steroid Biochem Mol Biol. 2010 Oct;122(1–3):91–99PubMedCrossRefGoogle Scholar
  51. 51.
    Kane DA, Lin CT, Anderson EJ, Kwak HB, Cox JH, Brophy PM, Hickner RC, Neufer PD, Cortright RN. Progesterone increases skeletal muscle mitochondrial H2O2 emission in nonmenopausal women. Am J Physiol Endocrinol Metab. 2011 Mar;300(3):E528–E535)PubMedCrossRefGoogle Scholar
  52. 52.
    Borst SE. Interventions for sarcopenia and muscle weakness in older people. Age Ageing. 2004;33(6):548–555.PubMedCrossRefGoogle Scholar
  53. 53.
    Corcoran MP, Lamon-Fava S, Fielding RA. (2007) Skeletal muscle lipid deposition and insulin resistance: effect of dietary fatty acids and exercise. Am J Clin Nutr;85(3):662–677.PubMedGoogle Scholar
  54. 54.
    Simoneau JA, Kelley DE.(1997) Altered glycolytic and oxidative capacities of skeletal muscle contribute to insulin resistance in NIDDM. J Appl Physiol 83:166–171PubMedGoogle Scholar
  55. 55.
    Trappe SW, Costill DL, Fink WJ, Pearson DR. (1995) Skeletal muscle characteristics among distance runners: a 20-yr follow-up study. J Appl Physiol; 78:823–828PubMedGoogle Scholar
  56. 56.
    Brehm A, Krssak M, Schmid AI, Nowotny P, Waldhäusl W, Roden M. (2006) Increased lipid availability impairs insulin-stimulated ATP synthesis in human skeletal muscle. Diabetes;55(1):136–140.PubMedCrossRefGoogle Scholar
  57. 57.
    Fleischman A, Johnsen S, Systrom DM, et al. (2007) Effects of a nucleoside reverse transcriptase inhibitor, stavudine, on glucose disposal and mitochondrial function in muscle of healthy adults. Am J Physiol Endocrinol Metab.;292(6):E1666–E1673.PubMedCrossRefGoogle Scholar

Copyright information

© Serdi and Springer Verlag France 2011

Authors and Affiliations

  • Angela Marie Abbatecola
    • 1
    • 7
  • G. Paolisso
    • 2
  • P. Fattoretti
    • 3
  • W. J. Evans
    • 4
  • V. Fiore
    • 5
  • L. Dicioccio
    • 6
  • F. Lattanzio
    • 1
  1. 1.Scientific Direction-Italian National Research Center on Aging (INRCA)AnconaItaly
  2. 2.Department of Geriatric Medicine and Metabolic DiseasesSecond University of NaplesNaplesItaly
  3. 3.Neurobiology of Aging Laboratory and Cellular Bioenergetics Laboratory — Italian National Research Center on Aging (INRCA)AnconaItaly
  4. 4.Muscle Metabolism Discovery Unity, GlaxoSmithKline, Research Triangle Park, NC and Division of GeriatricsDuke University Medical CenterDurhamUSA
  5. 5.Department of Geriatric Medicine, Endocrinology and Metabolic Disease“A. Angelucci” HospitalSubiacoItaly
  6. 6.Department of Geriatric Medicine“Santa Scolastica” HospitalCassinoItaly
  7. 7.INRCA (Italian National Research Center on Aging), Scientific DirectionAnconaItaly

Personalised recommendations