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Muscle Quality in Aging: a Multi-Dimensional Approach to Muscle Functioning with Applications for Treatment

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Abstract

Aging is often accompanied by declines in physical functioning which impedes older adults’ quality of life, sense of independence, and ability to perform daily tasks. Age-related decreases in skeletal muscle quantity, termed sarcopenia, have traditionally been blamed for these physical decrements. However, recent evidence suggests that the quality of muscle tissue may be more functionally relevant than its quantity. ‘Muscle quality’ has been emerging as a means to elucidate and describe the intricate intramuscular changes associated with muscle performance in the context of aging and sarcopenia. While muscle quality has most commonly been defined in terms of muscle composition or relative strength, at the core, muscle quality really describes muscle’s ability to function. Skeletal muscle displays a strong structure–function relationship by which several architectural characteristics factor into its functional capacity. This review describes the structural, physiological, and functional determinants of muscle quality at the tissue and cellular level, while also introducing other novel parameters such as sarcomere spacing and integrity, circulating biomarkers, and the muscle quality index. Muscle qualitative features are described from the perspective of how physical exercise may improve muscle quality in older adults. This broad, multidimensional perspective of muscle quality in the context of aging and sarcopenia offers comprehensive insights for consideration and integration in developing improved prognostic tools for research and clinical care, while also promoting translational approaches to the design of novel targeted intervention strategies designed to maintain function and mobility into late life.

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References

  1. Baumgartner RN, Koehler KM, Gallagher D, et al. Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol. 1998;147(8):755–63.

    CAS  PubMed  Google Scholar 

  2. Janssen I. Influence of sarcopenia on the development of physical disability: the Cardiovascular Health Study. J Am Geriatr Soc. 2006;54(1):56–62.

    PubMed  Google Scholar 

  3. Cooper C, Fielding R, Visser M, et al. Tools in the assessment of sarcopenia. Calcif Tissue Int. 2013;93(3):201–10.

    PubMed Central  CAS  PubMed  Google Scholar 

  4. Barbat-Artigas S, Rolland Y, Zamboni M, et al. How to assess functional status: a new muscle quality index. J Nutr Health Aging. 2012;16(1):67–77.

    CAS  PubMed  Google Scholar 

  5. Correa-de-Araujo R, Hadley E. Skeletal muscle function deficit: a new terminology to embrace the evolving concepts of sarcopenia and age-related muscle dysfunction. J Gerontol A Biol Sci Med Sci. 2014;69(5):591–4.

    PubMed  Google Scholar 

  6. Maggio M, Lauretani F, Ceda GP. Sex hormones and sarcopenia in older persons. Curr Opin Clin Nutr Metab Care. 2013;16(1):3–13.

    CAS  PubMed  Google Scholar 

  7. Brotto M, Abreu EL. Sarcopenia: pharmacology of today and tomorrow. J Pharmacol Exp Ther. 2012;343(3):540–6.

    PubMed Central  CAS  PubMed  Google Scholar 

  8. Landi F, Marzetti E, Martone AM, et al. Exercise as a remedy for sarcopenia. Curr Opin Clin Nutr Metab Care. 2014;17(1):25–31.

    PubMed  Google Scholar 

  9. Rogers MA, Evans WJ. Changes in skeletal muscle with aging: effects of exercise training. Exerc Sport Sci Rev. 1993;21:65–102.

    CAS  PubMed  Google Scholar 

  10. Fried LP, Walston JD, Ferrucci LF. In: Halter JB, Ouslander JG, Tinetti ME, et al., editors. Hazzard’s geriatric medicine and gerontology. 6th ed. San Francisco: McGraw-Hill Professional; 2009. p. 631–45.

    Google Scholar 

  11. Rockwood K, Mitnitski A. Frailty in relation to the accumulation of deficits. J Gerontol A Biol Sci Med Sci. 2007;62(7):722–7.

    PubMed  Google Scholar 

  12. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146–56.

    CAS  PubMed  Google Scholar 

  13. Hogan DB, MacKnight C, Bergman H. Models, definitions, and criteria of frailty. Aging Clin Exp Res. 2003;15(3 Suppl):1–29.

    PubMed  Google Scholar 

  14. Marzetti E, Leeuwenburgh C. Skeletal muscle apoptosis, sarcopenia and frailty at old age. Exp Gerontol. 2006;41(12):1234–8.

    CAS  PubMed  Google Scholar 

  15. Hyatt RH, Whitelaw MN, Bhat A, et al. Association of muscle strength with functional status of elderly people. Age Ageing. 1990;19(5):330–6.

    CAS  PubMed  Google Scholar 

  16. Campbell AJ, Borrie MJ, Spears GF. Risk factors for falls in a community-based prospective study of people 70 years and older. J Gerontol. 1989;44(4):M112–7.

    CAS  PubMed  Google Scholar 

  17. Rantanen T, Guralnik JM, Ferrucci L, et al. Coimpairments: strength and balance as predictors of severe walking disability. J Gerontol A Biol Sci Med Sci. 1999;54(4):M172–6.

    CAS  PubMed  Google Scholar 

  18. Muhlberg W, Sieber C. Sarcopenia and frailty in geriatric patients: implications for training and prevention. Z Gerontol Geriatr. 2004;37(1):2–8.

    CAS  PubMed  Google Scholar 

  19. Karavirta L, Hakkinen K, Kauhanen A, et al. Individual responses to combined endurance and strength training in older adults. Med Sci Sports Exerc. 2011;43(3):484–90.

    PubMed  Google Scholar 

  20. Bortz WM 2nd. Disuse and aging. JAMA. 1982;248(10):1203–8.

    PubMed  Google Scholar 

  21. Melton LJ 3rd, Khosla S, Riggs BL. Epidemiology of sarcopenia. Mayo Clin Proc. 2000;75 Suppl:S10–2 (discussion S12–3).

    PubMed  Google Scholar 

  22. Roubenoff R, Hughes VA. Sarcopenia: current concepts. J Gerontol A Biol Sci Med Sci. 2000;55(12):M716–24.

    CAS  PubMed  Google Scholar 

  23. Frontera WR, Hughes VA, Lutz KJ, et al. A cross-sectional study of muscle strength and mass in 45–78-yr-old men and women. J Appl Physiol. 1991;71(2):644–50.

    CAS  PubMed  Google Scholar 

  24. Reed RL, Pearlmutter L, Yochum K, et al. The relationship between muscle mass and muscle strength in the elderly. J Am Geriatr Soc. 1991;39(6):555–61.

    CAS  PubMed  Google Scholar 

  25. Clark BC, Manini TM. Sarcopenia ≠ dynapenia. J Gerontol A Biol Sci Med Sci. 2008;63(8):829–34.

    PubMed  Google Scholar 

  26. Alley DE, Shardell MD, Peters KW, et al. Grip strength cutpoints for the identification of clinically relevant weakness. J Gerontol A Biol Sci Med Sci. 2014;69(5):559–66.

    PubMed Central  PubMed  Google Scholar 

  27. Clark BC, Manini TM. Functional consequences of sarcopenia and dynapenia in the elderly. Curr Opin Clin Nutr Metab Care. 2010;13(3):271–6.

    PubMed Central  PubMed  Google Scholar 

  28. Visser M, Goodpaster BH, Kritchevsky SB, et al. Muscle mass, muscle strength, and muscle fat infiltration as predictors of incident mobility limitations in well-functioning older persons. J Gerontol A Biol Sci Med Sci. 2005;60(3):324–33.

    PubMed  Google Scholar 

  29. Bassey EJ, Fiatarone MA, O’Neill EF, et al. Leg extensor power and functional performance in very old men and women. Clin Sci (Lond). 1992;82(3):321–7.

    CAS  Google Scholar 

  30. 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(25):1769–75.

    CAS  PubMed  Google Scholar 

  31. Foldvari M, Clark M, Laviolette LC, et al. Association of muscle power with functional status in community-dwelling elderly women. J Gerontol A Biol Sci Med Sci. 2000;55(4):M192–9.

    CAS  PubMed  Google Scholar 

  32. Newman AB, Kupelian V, Visser M, et al. Strength, but not muscle mass, is associated with mortality in the health, aging and body composition study cohort. J Gerontol A Biol Sci Med Sci. 2006;61(1):72–7.

    PubMed  Google Scholar 

  33. Goodpaster BH, Park SW, Harris TB, et al. The loss of skeletal muscle strength, mass, and quality in older adults: the health, aging and body composition study. J Gerontol A Biol Sci Med Sci. 2006;61(10):1059–64.

    PubMed  Google Scholar 

  34. Metter EJ, Lynch N, Conwit R, et al. Muscle quality and age: cross-sectional and longitudinal comparisons. J Gerontol A Biol Sci Med Sci. 1999;54(5):B207–18.

    CAS  PubMed  Google Scholar 

  35. Overend TJ, Cunningham DA, Kramer JF, et al. Knee extensor and knee flexor strength: cross-sectional area ratios in young and elderly men. J Gerontol. 1992;47(6):M204–10.

    CAS  PubMed  Google Scholar 

  36. Larsson L, Grimby G, Karlsson J. Muscle strength and speed of movement in relation to age and muscle morphology. J Appl Physiol. 1979;46(3):451–6.

    CAS  PubMed  Google Scholar 

  37. Delmonico MJ, Harris TB, Visser M, et al. Longitudinal study of muscle strength, quality, and adipose tissue infiltration. Am J Clin Nutr. 2009;90(6):1579–85.

    PubMed Central  CAS  PubMed  Google Scholar 

  38. Phillips SK, Woledge RC, Bruce SA, et al. A study of force and cross-sectional area of adductor pollicis muscle in female hip fracture patients. J Am Geriatr Soc. 1998;46(8):999–1002.

    CAS  PubMed  Google Scholar 

  39. Lexell J, Taylor CC, Sjostrom M. What is the cause of the ageing atrophy? Total number, size and proportion of different fiber types studied in whole vastus lateralis muscle from 15- to 83-year-old men. J Neurol Sci. 1988;84(2–3):275–94.

    CAS  PubMed  Google Scholar 

  40. Tomonaga M. Histochemical and ultrastructural changes in senile human skeletal muscle. J Am Geriatr Soc. 1977;25(3):125–31.

    CAS  PubMed  Google Scholar 

  41. Lexell J, Henriksson-Larsen K, Winblad B, et al. Distribution of different fiber types in human skeletal muscles: effects of aging studied in whole muscle cross sections. Muscle Nerve. 1983;6(8):588–95.

    CAS  PubMed  Google Scholar 

  42. Larsson L, Sjodin B, Karlsson J. Histochemical and biochemical changes in human skeletal muscle with age in sedentary males, age 22–65 years. Acta Physiol Scand. 1978;103(1):31–9.

    CAS  PubMed  Google Scholar 

  43. Kirkeby S, Garbarsch C. Aging affects different human muscles in various ways. An image analysis of the histomorphometric characteristics of fiber types in human masseter and vastus lateralis muscles from young adults and the very old. Histol Histopathol. 2000;15(1):61–71.

    CAS  PubMed  Google Scholar 

  44. Yu F, Hedstrom M, Cristea A, et al. Effects of ageing and gender on contractile properties in human skeletal muscle and single fibres. Acta Physiol (Oxf). 2007;190(3):229–41.

    CAS  Google Scholar 

  45. Kimball SR, Jefferson LS. Control of protein synthesis by amino acid availability. Curr Opin Clin Nutr Metab Care. 2002;5(1):63–7.

    CAS  PubMed  Google Scholar 

  46. Hasten DL, Pak-Loduca J, Obert KA, et al. 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(4):E620–6.

    CAS  PubMed  Google Scholar 

  47. Rooyackers OE, Adey DB, Ades PA, et al. Effect of age on in vivo rates of mitochondrial protein synthesis in human skeletal muscle. Proc Natl Acad Sci. 1996;93(26):15364–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  48. Welle S, Thornton C, Jozefowicz R, et al. Myofibrillar protein synthesis in young and old men. Am J Physiol. 1993;264(5 Pt 1):E693–8.

    CAS  PubMed  Google Scholar 

  49. 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):E790–800.

    CAS  PubMed  Google Scholar 

  50. Schaap LA, Pluijm SM, Deeg DJ, et al. Inflammatory markers and loss of muscle mass (sarcopenia) and strength. Am J Med. 2006;119(6):526 e9–17.

    Google Scholar 

  51. Bautmans I, Njemini R, Lambert M, et al. Circulating acute phase mediators and skeletal muscle performance in hospitalized geriatric patients. J Gerontol A Biol Sci Med Sci. 2005;60(3):361–7.

    PubMed  Google Scholar 

  52. Ferrucci L, Penninx BW, Volpato S, et al. Change in muscle strength explains accelerated decline of physical function in older women with high interleukin-6 serum levels. J Am Geriatr Soc. 2002;50(12):1947–54.

    PubMed  Google Scholar 

  53. Lang CH, Frost RA, Nairn AC, et al. TNF-alpha impairs heart and skeletal muscle protein synthesis by altering translation initiation. Am J Physiol Endocrinol Metab. 2002;282(2):E336–47.

    CAS  PubMed  Google Scholar 

  54. Roubenoff R. Catabolism of aging: is it an inflammatory process? Curr Opin Clin Nutr Metab Care. 2003;6(3):295–9.

    PubMed  Google Scholar 

  55. Visser M, Kritchevsky SB, Goodpaster BH, et al. Leg muscle mass and composition in relation to lower extremity performance in men and women aged 70–79: the health, aging and body composition study. J Am Geriatr Soc. 2002;50(5):897–904.

    PubMed  Google Scholar 

  56. Ramamurthy B, Larsson L. Detection of an aging-related increase in advanced glycation end products in fast- and slow-twitch skeletal muscles in the rat. Biogerontology. 2013;14(3):293–301.

    CAS  PubMed  Google Scholar 

  57. Scelsi R, Marchetti C, Poggi P. Histochemical and ultrastructural aspects of m. vastus lateralis in sedentary old people (age 65–89 years). Acta Neuropathol. 1980;51(2):99–105.

    CAS  PubMed  Google Scholar 

  58. Burd NA, Gorissen SH, van Loon LJ. Anabolic resistance of muscle protein synthesis with aging. Exerc Sport Sci Rev. 2013;41(3):169–73.

    PubMed  Google Scholar 

  59. Yarasheski KE. Exercise, aging, and muscle protein metabolism. J Gerontol A Biol Sci Med Sci. 2003;58(10):M918–22.

    PubMed  Google Scholar 

  60. Pette D, Staron RS. Myosin isoforms, muscle fiber types, and transitions. Microsc Res Tech. 2000;50(6):500–9.

    CAS  PubMed  Google Scholar 

  61. Krivickas LS, Suh D, Wilkins J, et al. Age- and gender-related differences in maximum shortening velocity of skeletal muscle fibers. Am J Phys Med Rehabil. 2001;80(6):447–55 (quiz 456–7).

    CAS  PubMed  Google Scholar 

  62. Lexell J, Downham D, Sjostrom M. Distribution of different fibre types in human skeletal muscles. Fibre type arrangement in m. vastus lateralis from three groups of healthy men between 15 and 83 years. J Neurol Sci. 1986;72(2–3):211–22.

    CAS  PubMed  Google Scholar 

  63. Larsson L, Salviati G. Effects of age on calcium transport activity of sarcoplasmic reticulum in fast- and slow-twitch rat muscle fibres. J Physiol. 1989;419:253–64.

    PubMed Central  CAS  PubMed  Google Scholar 

  64. Hook P, Li X, Sleep J, et al. The effect of age on in vitro motility speed of slow myosin extracted from single rat soleus fibres. Acta Physiol Scand. 1999;167(4):325–6.

    CAS  PubMed  Google Scholar 

  65. Burke RE, Levine DN, Zajac FE 3rd. Mammalian motor units: physiological-histochemical correlation in three types in cat gastrocnemius. Science. 1971;174(10):709–12.

    CAS  PubMed  Google Scholar 

  66. Tomlinson BE, Irving D. The numbers of limb motor neurons in the human lumbosacral cord throughout life. J Neurol Sci. 1977;34(2):213–9.

    CAS  PubMed  Google Scholar 

  67. Gawel M, Kostera-Pruszczyk A. Effect of age and gender on the number of motor units in healthy subjects estimated by the multipoint incremental MUNE method. J Clin Neurophysiol. 2014;31(3):272–8.

    PubMed  Google Scholar 

  68. Campbell MJ, McComas AJ, Petito F. Physiological changes in ageing muscles. J Neurol Neurosurg Psychiatry. 1973;36(2):174–82.

    PubMed Central  CAS  PubMed  Google Scholar 

  69. Mosole S, Carraro U, Kern H, et al. Long-term high-level exercise promotes muscle reinnervation with age. J Neuropathol Exp Neurol. 2014;73(4):284–94.

    CAS  PubMed  Google Scholar 

  70. Mittal KR, Logmani FH. Age-related reduction in 8th cervical ventral nerve root myelinated fiber diameters and numbers in man. J Gerontol. 1987;42(1):8–10.

    CAS  PubMed  Google Scholar 

  71. Arnold N, Harriman DG. The incidence of abnormality in control human peripheral nerves studied by single axon dissection. J Neurol Neurosurg Psychiatry. 1970;33(1):55–61.

    PubMed Central  CAS  PubMed  Google Scholar 

  72. Deschenes MR. Motor unit and neuromuscular junction remodeling with aging. Curr Aging Sci. 2011;4(3):209–20.

    CAS  PubMed  Google Scholar 

  73. Delbono O. Regulation of excitation contraction coupling by insulin-like growth factor-1 in aging skeletal muscle. J Nutr Health Aging. 2000;4(3):162–4.

    CAS  PubMed  Google Scholar 

  74. McComas AJ, Upton AR, Sica RE. Motoneurone disease and ageing. Lancet. 1973;2(7844):1477–80.

    CAS  PubMed  Google Scholar 

  75. Lynch NA, Metter EJ, Lindle RS, et al. Muscle quality. I. Age-associated differences between arm and leg muscle groups. J Appl Physiol (1985). 1999;86(1):188–94.

    CAS  Google Scholar 

  76. Tracy BL, Ivey FM, Hurlbut D, et al. Muscle quality. II. Effects of strength training in 65–75-yr-old men and women. J Appl Physiol. 1999;86(1):195–201.

    CAS  PubMed  Google Scholar 

  77. Lindle RS, Metter EJ, Lynch NA, et al. Age and gender comparisons of muscle strength in 654 women and men aged 20–93 yr. J Appl Physiol. 1997;83(5):1581–7.

    CAS  PubMed  Google Scholar 

  78. Lynch NA, Metter EJ, Lindle RS, et al. Muscle quality. I. Age-associated differences between arm and leg muscle groups. J Appl Physiol. 1999;86(1):188–94.

    CAS  PubMed  Google Scholar 

  79. Misic MM, Rosengren KS, Woods JA, et al. Muscle quality, aerobic fitness and fat mass predict lower-extremity physical function in community-dwelling older adults. Gerontology. 2007;53(5):260–6.

    PubMed  Google Scholar 

  80. Barbat-Artigas S, Rolland Y, Cesari M, et al. Clinical relevance of different muscle strength indexes and functional impairment in women aged 75 years and older. J Gerontol A Biol Sci Med Sci. 2013;68(7):811–9.

    PubMed  Google Scholar 

  81. Estrada M, Kleppinger A, Judge JO, et al. Functional impact of relative versus absolute sarcopenia in healthy older women. J Am Geriatr Soc. 2007;55(11):1712–9.

    PubMed  Google Scholar 

  82. Barbat-Artigas S, Rolland Y, Vellas B, et al. Muscle quantity is not synonymous with muscle quality. J Am Med Dir Assoc. 2013;14(11):852 e1–7.

    Google Scholar 

  83. Yamauchi J, Mishima C, Nakayama S, et al. Aging-related differences in maximum force, unloaded velocity and power of human leg multi-joint movement. Gerontology. 2010;56(2):167–74.

    PubMed  Google Scholar 

  84. Takai Y, Ohta M, Akagi R, et al. Sit-to-stand test to evaluate knee extensor muscle size and strength in the elderly: a novel approach. J Physiol Anthropol. 2009;28(3):123–8.

    PubMed  Google Scholar 

  85. Fragala MS, Fukuda DH, Stout JR, et al. Muscle quality index improves with resistance exercise training in older adults. Exp Gerontol. 2014;53:1–6.

    PubMed  Google Scholar 

  86. Kyle UG, Genton L, Hans D, et al. Total body mass, fat mass, fat-free mass, and skeletal muscle in older people: cross-sectional differences in 60-year-old persons. J Am Geriatr Soc. 2001;49(12):1633–40.

    CAS  PubMed  Google Scholar 

  87. Fragala MS, Clark MH, Walsh SJ, et al. Gender differences in anthropometric predictors of physical performance in older adults. Gend Med. 2012;9(6):445–56.

    PubMed Central  PubMed  Google Scholar 

  88. Newman AB, Haggerty CL, Goodpaster B, et al. Strength and muscle quality in a well-functioning cohort of older adults: the Health, Aging and Body Composition Study. J Am Geriatr Soc. 2003;51(3):323–30.

    PubMed  Google Scholar 

  89. Villareal DT, Apovian CM, Kushner RF, et al. Obesity in older adults: technical review and position statement of the American Society for Nutrition and NAASO, the Obesity Society. Obes Res. 2005;13(11):1849–63.

    PubMed  Google Scholar 

  90. Zizza CA, Herring A, Stevens J, et al. Obesity affects nursing-care facility admission among whites but not blacks. Obes Res. 2002;10(8):816–23.

    PubMed  Google Scholar 

  91. Forsberg AM, Nilsson E, Werneman J, et al. Muscle composition in relation to age and sex. Clin Sci (Lond). 1991;81(2):249–56.

    CAS  Google Scholar 

  92. Goodpaster BH, Carlson CL, Visser M, et al. Attenuation of skeletal muscle and strength in the elderly: the Health ABC Study. J Appl Physiol. 2001;90(6):2157–65.

    CAS  PubMed  Google Scholar 

  93. Fuller NJ, Hardingham CR, Graves M, et al. Assessment of limb muscle and adipose tissue by dual-energy X-ray absorptiometry using magnetic resonance imaging for comparison. Int J Obes Relat Metab Disord. 1999;23(12):1295–302.

    CAS  PubMed  Google Scholar 

  94. Ruan XY, Gallagher D, Harris T, et al. Estimating whole body intermuscular adipose tissue from single cross-sectional magnetic resonance images. J Appl Physiol. 2007;102(2):748–54.

    PubMed Central  PubMed  Google Scholar 

  95. Kim J, Wang Z, Heymsfield SB, et al. Total-body skeletal muscle mass: estimation by a new dual-energy X-ray absorptiometry method. Am J Clin Nutr. 2002;76(2):378–83.

    CAS  PubMed  Google Scholar 

  96. Heymsfield SB, Wang Z, Baumgartner RN, et al. Human body composition: advances in models and methods. Annu Rev Nutr. 1997;17:527–58.

    CAS  PubMed  Google Scholar 

  97. Goodpaster BH, Thaete FL, Kelley DE. Composition of skeletal muscle evaluated with computed tomography. Ann N Y Acad Sci. 2000;904:18–24.

    CAS  PubMed  Google Scholar 

  98. Overend TJ, Cunningham DA, Paterson DH, et al. Thigh composition in young and elderly men determined by computed tomography. Clin Physiol. 1992;12(6):629–40.

    CAS  PubMed  Google Scholar 

  99. Visser M, Pahor M, Tylavsky F, et al. One- and two-year change in body composition as measured by DXA in a population-based cohort of older men and women. J Appl Physiol. 2003;94(6):2368–74.

    PubMed  Google Scholar 

  100. Goodpaster BH, Kelley DE, Thaete FL, et al. Skeletal muscle attenuation determined by computed tomography is associated with skeletal muscle lipid content. J Appl Physiol. 2000;89(1):104–10.

    CAS  PubMed  Google Scholar 

  101. Nordal HJ, Dietrichson P, Eldevik P, et al. Fat infiltration, atrophy and hypertrophy of skeletal muscles demonstrated by X-ray computed tomography in neurological patients. Acta Neurol Scand. 1988;77(2):115–22.

    CAS  PubMed  Google Scholar 

  102. Goodpaster BH, Theriault R, Watkins SC, et al. Intramuscular lipid content is increased in obesity and decreased by weight loss. Metabolism. 2000;49(4):467–72.

    CAS  PubMed  Google Scholar 

  103. Goodpaster BH, Chomentowski P, Ward BK, et al. Effects of physical activity on strength and skeletal muscle fat infiltration in older adults: a randomized controlled trial. J Appl Physiol. 2008;105(5):1498–503.

    PubMed Central  PubMed  Google Scholar 

  104. Hilton TN, Tuttle LJ, Bohnert KL, et al. Excessive adipose tissue infiltration in skeletal muscle in individuals with obesity, diabetes mellitus, and peripheral neuropathy: association with performance and function. Phys Ther. 2008;88(11):1336–44.

    PubMed Central  PubMed  Google Scholar 

  105. Lauretani F, Bandinelli S, Bartali B, et al. Axonal degeneration affects muscle density in older men and women. Neurobiol Aging. 2006;27(8):1145–54.

    PubMed Central  PubMed  Google Scholar 

  106. Schrager MA, Metter EJ, Simonsick E, et al. Sarcopenic obesity and inflammation in the InCHIANTI study. J Appl Physiol. 2007;102(3):919–25.

    PubMed Central  PubMed  Google Scholar 

  107. Cesari M, Leeuwenburgh C, Lauretani F, et al. Frailty syndrome and skeletal muscle: results from the Invecchiare in Chianti study. Am J Clin Nutr. 2006;83(5):1142–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  108. Boesch C, Machann J, Vermathen P, et al. Role of proton MR for the study of muscle lipid metabolism. NMR Biomed. 2006;19(7):968–88.

    CAS  PubMed  Google Scholar 

  109. Szczepaniak LS, Dobbins RL, Stein DT, et al. Bulk magnetic susceptibility effects on the assessment of intra- and extramyocellular lipids in vivo. Magn Reson Med. 2002;47(3):607–10.

    CAS  PubMed  Google Scholar 

  110. Pan DA, Lillioja S, Kriketos AD, et al. Skeletal muscle triglyceride levels are inversely related to insulin action. Diabetes. 1997;46(6):983–8.

    CAS  PubMed  Google Scholar 

  111. Nakagawa Y, Hattori M, Harada K, et al. Age-related changes in intramyocellular lipid in humans by in vivo H-MR spectroscopy. Gerontology. 2007;53(4):218–23.

    CAS  PubMed  Google Scholar 

  112. Crane JD, Devries MC, Safdar A, et al. The effect of aging on human skeletal muscle mitochondrial and intramyocellular lipid ultrastructure. J Gerontol A Biol Sci Med Sci. 2010;65(2):119–28.

    PubMed  Google Scholar 

  113. Conley KE, Jubrias SA, Esselman PC. Oxidative capacity and ageing in human muscle. J Physiol. 2000;526(Pt 1):203–10.

    PubMed Central  CAS  PubMed  Google Scholar 

  114. Fukunaga T, Kawakami Y, Kuno S, et al. Muscle architecture and function in humans. J Biomech. 1997;30(5):457–63.

    CAS  PubMed  Google Scholar 

  115. Gans C, Gaunt AS. Muscle architecture in relation to function. J Biomech. 1991;24(Suppl 1):53–65.

    PubMed  Google Scholar 

  116. Lieber RL, Friden J. Functional and clinical significance of skeletal muscle architecture. Muscle Nerve. 2000;23(11):1647–66.

    CAS  PubMed  Google Scholar 

  117. Gans C, de Vree F. Functional bases of fiber length and angulation in muscle. J Morphol. 1987;192(1):63–85.

    CAS  PubMed  Google Scholar 

  118. Kawakami Y, Abe T, Fukunaga T. Muscle-fiber pennation angles are greater in hypertrophied than in normal muscles. J Appl Physiol. 1993;74(6):2740–4.

    CAS  PubMed  Google Scholar 

  119. Narici MV, Maganaris CN, Reeves ND, et al. Effect of aging on human muscle architecture. J Appl Physiol. 2003;95(6):2229–34.

    CAS  PubMed  Google Scholar 

  120. Reeves ND, Narici MV, Maganaris CN. In vivo human muscle structure and function: adaptations to resistance training in old age. Exp Physiol. 2004;89(6):675–89.

    CAS  PubMed  Google Scholar 

  121. Narici MV, Maganaris CN. Adaptability of elderly human muscles and tendons to increased loading. J Anat. 2006;208(4):433–43.

    PubMed Central  PubMed  Google Scholar 

  122. Scanlon TC, Fragala MS, Stout JR, et al. Muscle architecture and strength: adaptations to short-term resistance training in older adults. Muscle Nerve. 2014;49(4):584–92.

    PubMed  Google Scholar 

  123. Ochala J, Frontera WR, Dorer DJ, et al. Single skeletal muscle fiber elastic and contractile characteristics in young and older men. J Gerontol A Biol Sci Med Sci. 2007;62(4):375–81.

    PubMed  Google Scholar 

  124. Frontera WR, Reid KF, Phillips EM, et al. Muscle fiber size and function in elderly humans: a longitudinal study. J Appl Physiol. 2008;105(2):637–42.

    PubMed Central  PubMed  Google Scholar 

  125. D’Antona G, Pellegrino MA, Carlizzi CN, et al. Deterioration of contractile properties of muscle fibres in elderly subjects is modulated by the level of physical activity. Eur J Appl Physiol. 2007;100(5):603–11.

    PubMed  Google Scholar 

  126. Larsson L, Li X, Frontera WR. Effects of aging on shortening velocity and myosin isoform composition in single human skeletal muscle cells. Am J Physiol. 1997;272(2 Pt 1):C638–49.

    CAS  PubMed  Google Scholar 

  127. Wang K, Ramirez-Mitchell R. A network of transverse and longitudinal intermediate filaments is associated with sarcomeres of adult vertebrate skeletal muscle. J Cell Biol. 1983;96(2):562–70.

    CAS  PubMed  Google Scholar 

  128. Huxley AF. Muscle structure and theories of contraction. Prog Biophys Chem. 1957;7:255–318.

    CAS  Google Scholar 

  129. Clark KA, McElhinny AS, Beckerle MC, et al. Striated muscle cytoarchitecture: an intricate web of form and function. Annu Rev Cell Dev Biol. 2002;18:637–706.

    CAS  PubMed  Google Scholar 

  130. Frank D, Kuhn C, Katus HA, et al. The sarcomeric Z-disc: a nodal point in signalling and disease. J Mol Med. 2006;84(6):446–68.

    CAS  PubMed  Google Scholar 

  131. Au Y. The muscle ultrastructure: a structural perspective of the sarcomere. Cell Mol Life Sci. 2004;61(24):3016–33.

    CAS  PubMed  Google Scholar 

  132. Luther PK, Padron R, Ritter S, et al. Heterogeneity of Z-band structure within a single muscle sarcomere: implications for sarcomere assembly. J Mol Biol. 2003;332(1):161–9.

    CAS  PubMed  Google Scholar 

  133. Gordon AM, Huxley AF, Julian FJ. The variation in isometric tension with sarcomere length in vertebrate muscle fibres. J Physiol. 1966;184(1):170–92.

    PubMed Central  CAS  PubMed  Google Scholar 

  134. Herzog W, Kamal S, Clarke HD. Myofilament lengths of cat skeletal muscle: theoretical considerations and functional implications. J Biomech. 1992;25(8):945–8.

    CAS  PubMed  Google Scholar 

  135. Kragstrup TW, Kjaer M, Mackey AL. Structural, biochemical, cellular, and functional changes in skeletal muscle extracellular matrix with aging. Scand J Med Sci Sports. 2011;21(6):749–57.

    CAS  PubMed  Google Scholar 

  136. Tanner BC, Daniel TL, Regnier M. Sarcomere lattice geometry influences cooperative myosin binding in muscle. PLoS Comput Biol. 2007;3(7):e115.

    PubMed Central  PubMed  Google Scholar 

  137. Visser M, Langlois J, Guralnik JM, et al. High body fatness, but not low fat-free mass, predicts disability in older men and women: the Cardiovascular Health Study. Am J Clin Nutr. 1998;68(3):584–90.

    CAS  PubMed  Google Scholar 

  138. Plotnikov SV, Kenny AM, Walsh SJ, et al. Measurement of muscle disease by quantitative second-harmonic generation imaging. J Biomed Opt. 2008;13(4):044018.

    PubMed  Google Scholar 

  139. Gollapudi SK, Lin DC. Experimental determination of sarcomere force-length relationship in type-I human skeletal muscle fibers. J Biomech. 2009;42(13):2011–6.

    PubMed  Google Scholar 

  140. Cartwright MS, Demar S, Griffin LP, et al. Validity and reliability of nerve and muscle ultrasound. Muscle Nerve. 2013;47(4):515–21.

    PubMed  Google Scholar 

  141. Scott JM, Martin DS, Ploutz-Snyder R, et al. Reliability and validity of panoramic ultrasound for muscle quantification. Ultrasound Med Biol. 2012;38(9):1656–61.

    PubMed  Google Scholar 

  142. Pillen S, Tak RO, Zwarts MJ, et al. Skeletal muscle ultrasound: correlation between fibrous tissue and echo intensity. Ultrasound Med Biol. 2009;35(3):443–6.

    PubMed  Google Scholar 

  143. Rosenberg JG, Ryan ED, Sobolewski EJ, et al. Reliability of panoramic ultrasound imaging to simultaneously examine muscle size and quality of the medial gastrocnemius. Muscle Nerve. 2014;49(5):736–40.

    PubMed  Google Scholar 

  144. Pillen S, van Dijk JP, Weijers G, et al. Quantitative gray-scale analysis in skeletal muscle ultrasound: a comparison study of two ultrasound devices. Muscle Nerve. 2009;39(6):781–6.

    PubMed  Google Scholar 

  145. Cadore EL, Izquierdo M, Conceicao M, et al. Echo intensity is associated with skeletal muscle power and cardiovascular performance in elderly men. Exp Gerontol. 2012;47(6):473–8.

    PubMed  Google Scholar 

  146. Trip J, Pillen S, Faber CG, et al. Muscle ultrasound measurements and functional muscle parameters in non-dystrophic myotonias suggest structural muscle changes. Neuromuscul Disord. 2009;19(7):462–7.

    CAS  PubMed  Google Scholar 

  147. Roth SM, Martel GF, Rogers MA. Muscle biopsy and muscle fiber hypercontraction: a brief review. Eur J Appl Physiol. 2000;83(4–5):239–45.

    CAS  PubMed  Google Scholar 

  148. Mouton P. Principles and practices of unbiased stereology. An introduction for bioscientists. Baltimore: Johns Hopkins University Press; 2002.

    Google Scholar 

  149. Campagnola PJ, Loew LM. Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms. Nat Biotechnol. 2003;21(11):1356–60.

    CAS  PubMed  Google Scholar 

  150. Both M, Vogel M, Friedrich O, et al. Second harmonic imaging of intrinsic signals in muscle fibers in situ. J Biomed Opt. 2004;9(5):882–92.

    PubMed  Google Scholar 

  151. Greenhalgh C, Prent N, Green C, et al. Influence of semicrystalline order on the second-harmonic generation efficiency in the anisotropic bands of myocytes. Appl Opt. 2007;46(10):1852–9.

    PubMed  Google Scholar 

  152. Plotnikov S, Juneja V, Isaacson AB, et al. Optical clearing for improved contrast in second harmonic generation imaging of skeletal muscle. Biophys J. 2006;90(1):328–39.

    PubMed Central  CAS  PubMed  Google Scholar 

  153. Plotnikov SV, Millard AC, Campagnola PJ, et al. Characterization of the myosin-based source for second-harmonic generation from muscle sarcomeres. Biophys J. 2006;90(2):693–703.

    PubMed Central  CAS  PubMed  Google Scholar 

  154. Mohler W, Millard AC, Campagnola PJ. Second harmonic generation imaging of endogenous structural proteins. Methods. 2003;29(1):97–109.

    CAS  PubMed  Google Scholar 

  155. Liu W, Raben N, Ralston E. Quantitative evaluation of skeletal muscle defects in second harmonic generation images. J Biomed Opt. 2013;18(2):26005.

    PubMed  Google Scholar 

  156. Buttgereit A, Weber C, Friedrich O. A novel quantitative morphometry approach to assess regeneration in dystrophic skeletal muscle. Neuromuscul Disord. 2014;24(7):596–603.

    PubMed  Google Scholar 

  157. Nan X, Cheng JX, Xie XS. Vibrational imaging of lipid droplets in live fibroblast cells with coherent anti-Stokes Raman scattering microscopy. J Lipid Res. 2003;44(11):2202–8.

    CAS  PubMed  Google Scholar 

  158. Flusberg BA, Cocker ED, Piyawattanametha W, et al. Fiber-optic fluorescence imaging. Nat Methods. 2005;2(12):941–50.

    PubMed Central  CAS  PubMed  Google Scholar 

  159. Fu L, Gan X, Gu M. Use of a single-mode fiber coupler for second-harmonic-generation microscopy. Opt Lett. 2005;30(4):385–7.

    PubMed  Google Scholar 

  160. Rothstein EC, Nauman M, Chesnick S, et al. Multi-photon excitation microscopy in intact animals. J Microsc. 2006;222(Pt 1):58–64.

    PubMed Central  PubMed  Google Scholar 

  161. Llewellyn ME, Barretto RP, Delp SL, et al. Minimally invasive high-speed imaging of sarcomere contractile dynamics in mice and humans. Nature. 2008;454(7205):784–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  162. Cromie MJ, Sanchez GN, Schnitzer MJ, et al. Sarcomere lengths in human extensor carpi radialis brevis measured by microendoscopy. Muscle Nerve. 2013;48(2):286–92.

    PubMed  Google Scholar 

  163. Cesari M, Fielding RA, Pahor M, et al. Biomarkers of sarcopenia in clinical trials-recommendations from the International Working Group on Sarcopenia. J Cachexia Sarcopenia Muscle. 2012;3(3):181–90.

    PubMed Central  PubMed  Google Scholar 

  164. Morley JE, Malmstrom TK. Frailty, sarcopenia, and hormones. Endocrinol Metab Clin N Am. 2013;42(2):391–405.

    Google Scholar 

  165. Sato K, Iemitsu M. Exercise and sex steroid hormones in skeletal muscle. J Steroid Biochem Mol Biol. 2015;145:200–5.

    CAS  PubMed  Google Scholar 

  166. Hameed M, Harridge SD, Goldspink G. Sarcopenia and hypertrophy: a role for insulin-like growth factor-1 in aged muscle? Exerc Sport Sci Rev. 2002;30(1):15–9.

    PubMed  Google Scholar 

  167. Nass R. Growth hormone axis and aging. Endocrinol Metab Clin N Am. 2013;42(2):187–99.

    CAS  Google Scholar 

  168. Michaud M, Balardy L, Moulis G, et al. Proinflammatory cytokines, aging, and age-related diseases. J Am Med Dir Assoc. 2013;14(12):877–82.

    PubMed  Google Scholar 

  169. Nelson ME, Fiatarone MA, Layne JE, et al. Analysis of body-composition techniques and models for detecting change in soft tissue with strength training. Am J Clin Nutr. 1996;63(5):678–86.

    CAS  PubMed  Google Scholar 

  170. Prockop DJ, Kivirikko KI, Tuderman L, et al. The biosynthesis of collagen and its disorders (second of two parts). N Engl J Med. 1979;301(2):77–85.

    CAS  PubMed  Google Scholar 

  171. De la Haba G, Kamali HM, Tiede DM. Myogenesis of avian striated muscle in vitro: role of collagen in myofiber formation. Proc Natl Acad Sci. 1975;72(7):2729–32.

    PubMed Central  PubMed  Google Scholar 

  172. Bhasin S, He EJ, Kawakubo M, et al. N-terminal propeptide of type III procollagen as a biomarker of anabolic response to recombinant human GH and testosterone. J Clin Endocrinol Metab. 2009;94(11):4224–33.

    PubMed Central  CAS  PubMed  Google Scholar 

  173. Bolliger MF, Zurlinden A, Luscher D, et al. Specific proteolytic cleavage of agrin regulates maturation of the neuromuscular junction. J Cell Sci. 2010;123(Pt 22):3944–55.

    CAS  PubMed  Google Scholar 

  174. Butikofer L, Zurlinden A, Bolliger MF, et al. Destabilization of the neuromuscular junction by proteolytic cleavage of agrin results in precocious sarcopenia. FASEB J. 2011;25(12):4378–93.

    CAS  PubMed  Google Scholar 

  175. Hettwer S, Dahinden P, Kucsera S, et al. Elevated levels of a C-terminal agrin fragment identifies a new subset of sarcopenia patients. Exp Gerontol. 2013;48(1):69–75.

    CAS  PubMed  Google Scholar 

  176. Drey M, Sieber CC, Bauer JM, et al. C-terminal Agrin Fragment as a potential marker for sarcopenia caused by degeneration of the neuromuscular junction. Exp Gerontol. 2013;48(1):76–80.

    CAS  PubMed  Google Scholar 

  177. Fragala MS, Jajtner AR, Beyer KS, et al. Biomarkers of muscle quality: N-terminal propeptide of type III procollagen and C-terminal agrin fragment responses to resistance exercise training in older adults. J Cachexia Sarcopenia Muscle. 2014;5(2):139–48.

    PubMed Central  PubMed  Google Scholar 

  178. Jones TE, Stephenson KW, King JG, et al. Sarcopenia–mechanisms and treatments. J Geriatr Phys Ther. 2009;32(2):83–9.

    PubMed  Google Scholar 

  179. Voznesensky M, Walsh S, Dauser D, et al. The association between dehydroepiandosterone and frailty in older men and women. Age Ageing. 2009;38(4):401–6.

    PubMed Central  CAS  PubMed  Google Scholar 

  180. 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(12):M772–7.

    PubMed  Google Scholar 

  181. Perrini S, Laviola L, Natalicchio A, et al. Associated hormonal declines in aging: DHEAS. J Endocrinol Invest. 2005;28(3 Suppl):85–93.

    CAS  PubMed  Google Scholar 

  182. Baker WL, Karan S, Kenny AM. Effect of dehydroepiandrosterone on muscle strength and physical function in older adults: a systematic review. J Am Geriatr Soc. 2011;59(6):997–1002.

    PubMed  Google Scholar 

  183. Kenny AM, Dawson L, Kleppinger A, et al. Prevalence of sarcopenia and predictors of skeletal muscle mass in nonobese women who are long-term users of estrogen-replacement therapy. J Gerontol A Biol Sci Med Sci. 2003;58(5):M436–40.

    PubMed  Google Scholar 

  184. Kenny AM, Kleppinger A, Wang Y, et al. Effects of ultra-low-dose estrogen therapy on muscle and physical function in older women. J Am Geriatr Soc. 2005;53(11):1973–7.

    PubMed  Google Scholar 

  185. Taaffe DR, Newman AB, Haggerty CL, et al. Estrogen replacement, muscle composition, and physical function: the Health ABC Study. Med Sci Sports Exerc. 2005;37(10):1741–7.

    CAS  PubMed  Google Scholar 

  186. Miljkovic I, Cauley JA, Dressen AS, et al. Bioactive androgens and glucuronidated androgen metabolites are associated with subcutaneous and ectopic skeletal muscle adiposity among older black men. Metabolism. 2011;60(8):1178–85.

    PubMed Central  CAS  PubMed  Google Scholar 

  187. Kenny AM, Kleppinger A, Annis K, et al. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels, low bone mass, and physical frailty. J Am Geriatr Soc. 2010;58(6):1134–43.

    PubMed Central  PubMed  Google Scholar 

  188. Schroeder ET, Terk M, Sattler FR. Androgen therapy improves muscle mass and strength but not muscle quality: results from two studies. Am J Physiol Endocrinol Metab. 2003;285(1):E16–24.

    CAS  PubMed  Google Scholar 

  189. Borst SE. Interventions for sarcopenia and muscle weakness in older people. Age Ageing. 2004;33(6):548–55.

    PubMed  Google Scholar 

  190. Pollanen E, Sipila S, Alen M, et al. Differential influence of peripheral and systemic sex steroids on skeletal muscle quality in pre- and postmenopausal women. Aging Cell. 2011;10(4):650–60.

    CAS  PubMed  Google Scholar 

  191. Lynch GS. Update on emerging drugs for sarcopenia—age-related muscle wasting. Expert Opin Emerg Drugs. 2008;13(4):655–73.

    CAS  PubMed  Google Scholar 

  192. Studenski SA, Peters KW, Alley DE, et al. The FNIH sarcopenia project: rationale, study description, conference recommendations, and final estimates. J Gerontol A Biol Sci Med Sci. 2014;69(5):547–58.

    PubMed Central  PubMed  Google Scholar 

  193. Vellas B, Pahor M, Manini T, et al. Designing pharmaceutical trials for sarcopenia in frail older adults: EU/US Task Force recommendations. J Nutr Health Aging. 2013;17(7):612–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  194. Brass EP, Sietsema KE. Considerations in the development of drugs to treat sarcopenia. J Am Geriatr Soc. 2011;59(3):530–5.

    PubMed  Google Scholar 

  195. Sayer AA, Robinson SM, Patel HP, et al. New horizons in the pathogenesis, diagnosis and management of sarcopenia. Age Ageing. 2013;42(2):145–50.

    PubMed Central  PubMed  Google Scholar 

  196. Witham MD, Sumukadas D, McMurdo ME. ACE inhibitors for sarcopenia–as good as exercise training? Age Ageing. 2008;37(4):363–5.

    PubMed  Google Scholar 

  197. Brault JJ, Jespersen JG, Goldberg AL. Peroxisome proliferator-activated receptor gamma coactivator 1alpha or 1beta overexpression inhibits muscle protein degradation, induction of ubiquitin ligases, and disuse atrophy. J Biol Chem. 2010;285(25):19460–71.

    PubMed Central  CAS  PubMed  Google Scholar 

  198. Wissing ER, Millay DP, Vuagniaux G, et al. Debio-025 is more effective than prednisone in reducing muscular pathology in mdx mice. Neuromuscul Disord. 2010;20(11):753–60.

    PubMed Central  PubMed  Google Scholar 

  199. Cadilla R, Turnbull P. Selective androgen receptor modulators in drug discovery: medicinal chemistry and therapeutic potential. Curr Top Med Chem. 2006;6(3):245–70.

    CAS  PubMed  Google Scholar 

  200. Bhasin S, Jasuja R. Selective androgen receptor modulators as function promoting therapies. Curr Opin Clin Nutr Metab Care. 2009;12(3):232–40.

    PubMed Central  CAS  PubMed  Google Scholar 

  201. Marzetti E, Calvani R, Bernabei R, et al. Apoptosis in skeletal myocytes: a potential target for interventions against sarcopenia and physical frailty—a mini-review. Gerontology. 2012;58(2):99–106.

    CAS  PubMed  Google Scholar 

  202. Husom AD, Peters EA, Kolling EA, et al. Altered proteasome function and subunit composition in aged muscle. Arch Biochem Biophys. 2004;421(1):67–76.

    CAS  PubMed  Google Scholar 

  203. Lee EJ, De Winter JM, Buck D, et al. Fast skeletal muscle troponin activation increases force of mouse fast skeletal muscle and ameliorates weakness due to nebulin-deficiency. PLoS One. 2013;8(2):e55861.

    PubMed Central  CAS  PubMed  Google Scholar 

  204. Gurtan AM, Sharp PA. The role of miRNAs in regulating gene expression networks. J Mol Biol. 2013;425(19):3582–600.

    PubMed Central  CAS  PubMed  Google Scholar 

  205. Mercken EM, Majounie E, Ding J, et al. Age-associated miRNA alterations in skeletal muscle from rhesus monkeys reversed by caloric restriction. Aging (Albany NY). 2013;5(9):692–703.

    CAS  Google Scholar 

  206. Berardi E, Annibali D, Cassano M, et al. Molecular and cell-based therapies for muscle degenerations: a road under construction. Front Physiol. 2014;5:119.

    PubMed Central  PubMed  Google Scholar 

  207. Valdez G, Heyer MP, Feng G, et al. The role of muscle microRNAs in repairing the neuromuscular junction. PLoS One. 2014;9(3):e93140.

    PubMed Central  PubMed  Google Scholar 

  208. Volpi E, Mittendorfer B, Rasmussen BB, et al. The response of muscle protein anabolism to combined hyperaminoacidemia and glucose-induced hyperinsulinemia is impaired in the elderly. J Clin Endocrinol Metab. 2000;85(12):4481–90.

    PubMed Central  CAS  PubMed  Google Scholar 

  209. Cuthbertson D, Smith K, Babraj J, et al. Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. FASEB J. 2005;19(3):422–4.

    CAS  PubMed  Google Scholar 

  210. Casperson SL, Sheffield-Moore M, Hewlings SJ, et al. Leucine supplementation chronically improves muscle protein synthesis in older adults consuming the RDA for protein. Clin Nutr. 2012;31(4):512–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  211. Iglay HB, Apolzan JW, Gerrard DE, et al. Moderately increased protein intake predominately from egg sources does not influence whole body, regional, or muscle composition responses to resistance training in older people. J Nutr Health Aging. 2009;13(2):108–14.

    CAS  PubMed  Google Scholar 

  212. Stout JR, Graves SB, Cramer JT, et al. Effects of creatine supplementation on the onset of neuromuscular fatigue threshold and muscle strength in elderly men and women (64–86 years). J Nutr Health Aging. 2007;11(6):459–64.

    CAS  PubMed  Google Scholar 

  213. Gotshalk LA, Kraemer WJ, Mendonca MA, et al. Creatine supplementation improves muscular performance in older women. Eur J Appl Physiol. 2008;102(2):223–31.

    CAS  PubMed  Google Scholar 

  214. McCormack WP, Stout JR, Emerson NS, et al. Oral nutritional supplement fortified with beta-alanine improves physical working capacity in older adults: a randomized, placebo-controlled study. Exp Gerontol. 2013;48(9):933–9.

    CAS  PubMed  Google Scholar 

  215. Stout JR, Smith-Ryan AE, Fukuda DH, et al. Effect of calcium beta-hydroxy-beta-methylbutyrate (CaHMB) with and without resistance training in men and women 65+yrs: a randomized, double-blind pilot trial. Exp Gerontol. 2013;48(11):1303–10.

    CAS  PubMed  Google Scholar 

  216. Brosnan JT, Brosnan ME. Creatine: endogenous metabolite, dietary, and therapeutic supplement. Annu Rev Nutr. 2007;27:241–61.

    CAS  PubMed  Google Scholar 

  217. Harris RC, Tallon MJ, Dunnett M, et al. The absorption of orally supplied beta-alanine and its effect on muscle carnosine synthesis in human vastus lateralis. Amino Acids. 2006;30(3):279–89.

    CAS  PubMed  Google Scholar 

  218. Wilkinson DJ, Hossain T, Hill DS, et al. Effects of leucine and its metabolite beta-hydroxy-beta-methylbutyrate on human skeletal muscle protein metabolism. J Physiol. 2013;591(Pt 11):2911–23.

    PubMed Central  CAS  PubMed  Google Scholar 

  219. Rousseau JH, Kleppinger A, Kenny AM. Self-reported dietary intake of omega-3 fatty acids and association with bone and lower extremity function. J Am Geriatr Soc. 2009;57(10):1781–8.

    PubMed  Google Scholar 

  220. Hakkinen K, Kraemer WJ, Pakarinen A, et al. Effects of heavy resistance/power training on maximal strength, muscle morphology, and hormonal response patterns in 60–75-year-old men and women. Can J Appl Physiol. 2002;27(3):213–31.

    CAS  PubMed  Google Scholar 

  221. Sallinen J, Ojanen T, Karavirta L, et al. Muscle mass and strength, body composition and dietary intake in master strength athletes vs untrained men of different ages. J Sports Med Phys Fitness. 2008;48(2):190–6.

    CAS  PubMed  Google Scholar 

  222. Aagaard P, Suetta C, Caserotti P, et al. Role of the nervous system in sarcopenia and muscle atrophy with aging: strength training as a countermeasure. Scand J Med Sci Sports. 2010;20(1):49–64.

    CAS  PubMed  Google Scholar 

  223. de Vos NJ, Singh NA, Ross DA, et al. Optimal load for increasing muscle power during explosive resistance training in older adults. J Gerontol A Biol Sci Med Sci. 2005;60(5):638–47.

    PubMed  Google Scholar 

  224. Fielding RA. The role of progressive resistance training and nutrition in the preservation of lean body mass in the elderly. J Am Coll Nutr. 1995;14(6):587–94.

    CAS  PubMed  Google Scholar 

  225. Sullivan DH, Roberson PK, Johnson LE, et al. Effects of muscle strength training and testosterone in frail elderly males. Med Sci Sports Exerc. 2005;37(10):1664–72.

    CAS  PubMed  Google Scholar 

  226. American College of Sports M, Chodzko-Zajko WJ, Proctor DN, et al. American College of Sports Medicine position stand. Exercise and physical activity for older adults. Med Sci Sports Exerc. 2009;41(7):1510–30.

    Google Scholar 

  227. Sillanpaa E, Hakkinen A, Nyman K, et al. Body composition and fitness during strength and/or endurance training in older men. Med Sci Sports Exerc. 2008;40(5):950–8.

    PubMed  Google Scholar 

  228. Liu CJ, Latham NK. Progressive resistance strength training for improving physical function in older adults. Cochrane Database Syst Rev 2009(3):CD002759.

  229. Sharman MJ, Newton RU, Triplett-McBride T, et al. Changes in myosin heavy chain composition with heavy resistance training in 60–75-year-old men and women. Eur J Appl Physiol. 2001;84(1–2):127–32.

    CAS  PubMed  Google Scholar 

  230. Izquierdo M, Hakkinen K, Ibanez J, et al. Effects of strength training on muscle power and serum hormones in middle-aged and older men. J Appl Physiol (1985). 2001;90(4):1497–507.

    CAS  Google Scholar 

  231. Fiatarone MA, Marks EC, Ryan ND, et al. High-intensity strength training in nonagenarians. Effects on skeletal muscle. JAMA. 1990;263(22):3029–34.

    CAS  PubMed  Google Scholar 

  232. Morganti CM, Nelson ME, Fiatarone MA, et al. Strength improvements with 1 yr of progressive resistance training in older women. Med Sci Sports Exerc. 1995;27(6):906–12.

    CAS  PubMed  Google Scholar 

  233. Hakkinen K, Kallinen M, Izquierdo M, et al. Changes in agonist-antagonist EMG, muscle CSA, and force during strength training in middle-aged and older people. J Appl Physiol. 1998;84(4):1341–9.

    CAS  PubMed  Google Scholar 

  234. De Luca CJ, Kline JC, Contessa P. Transposed firing activation of motor units. J Neurophysiol. 2014;112(4):962–70.

    PubMed  Google Scholar 

  235. Hughes VA, Roubenoff R, Wood M, et al. Anthropometric assessment of 10-y changes in body composition in the elderly. Am J Clin Nutr. 2004;80(2):475–82.

    CAS  PubMed  Google Scholar 

  236. Hakkinen K, Kraemer WJ, Newton RU, et al. Changes in electromyographic activity, muscle fibre and force production characteristics during heavy resistance/power strength training in middle-aged and older men and women. Acta Physiol Scand. 2001;171(1):51–62.

    CAS  PubMed  Google Scholar 

  237. Frontera WR, Meredith CN, O’Reilly KP, et al. Strength conditioning in older men: skeletal muscle hypertrophy and improved function. J Appl Physiol (1985). 1988;64(3):1038–44.

    CAS  Google Scholar 

  238. Kraemer WJ, Hakkinen K, Newton RU, et al. Effects of heavy-resistance training on hormonal response patterns in younger vs. older men. J Appl Physiol. 1999;87(3):982–92.

    CAS  PubMed  Google Scholar 

  239. Kraemer WJ, Hakkinen K, Newton RU, et al. Effects of heavy-resistance training on hormonal response patterns in younger vs. older men. J Appl Physiol (1985). 1999;87(3):982–92.

    CAS  Google Scholar 

  240. Urso ML, Fiatarone Singh MA, Ding W, et al. Exercise training effects on skeletal muscle plasticity and IGF-1 receptors in frail elders. Age (Dordr). 2005;27(2):117–25.

    PubMed Central  Google Scholar 

  241. Bruusgaard JC, Liestol K, Gundersen K. Distribution of myonuclei and microtubules in live muscle fibers of young, middle-aged, and old mice. J Appl Physiol. 2006;100(6):2024–30.

    CAS  PubMed  Google Scholar 

  242. Malatesta M, Perdoni F, Muller S, et al. Nuclei of aged myofibres undergo structural and functional changes suggesting impairment in RNA processing. Eur J Histochem. 2009;53(2):97–106.

    CAS  PubMed  Google Scholar 

  243. Edgerton VR, Roy RR. Regulation of skeletal muscle fiber size, shape and function. J Biomech. 1991;24(Suppl 1):123–33.

    PubMed  Google Scholar 

  244. Schultz E. Satellite cell behavior during skeletal muscle growth and regeneration. Med Sci Sports Exerc. 1989;21(5 Suppl):S181–6.

    CAS  PubMed  Google Scholar 

  245. Qaisar R, Renaud G, Morine K, et al. Is functional hypertrophy and specific force coupled with the addition of myonuclei at the single muscle fiber level? FASEB J. 2012;26(3):1077–85.

    PubMed Central  CAS  PubMed  Google Scholar 

  246. Hall ZW, Ralston E. Nuclear domains in muscle cells. Cell. 1989;59(5):771–2.

    CAS  PubMed  Google Scholar 

  247. Kadi F, Schjerling P, Andersen LL, et al. The effects of heavy resistance training and detraining on satellite cells in human skeletal muscles. J Physiol. 2004;558(Pt 3):1005–12.

    PubMed Central  CAS  PubMed  Google Scholar 

  248. Ralston E, Lu Z, Biscocho N, et al. Blood vessels and desmin control the positioning of nuclei in skeletal muscle fibers. J Cell Physiol. 2006;209(3):874–82.

    CAS  PubMed  Google Scholar 

  249. Atherton GW, James NT. Stereological analysis of the number of nuclei in skeletal muscle fibres. Acta Anat (Basel). 1980;107(2):236–40.

    CAS  Google Scholar 

  250. Burleigh IG. Observations on the number of nuclei within the fibres of some red and white muscles. J Cell Sci. 1977;23:269–84.

    CAS  PubMed  Google Scholar 

  251. Tseng BS, Kasper CE, Edgerton VR. Cytoplasm-to-myonucleus ratios and succinate dehydrogenase activities in adult rat slow and fast muscle fibers. Cell Tissue Res. 1994;275(1):39–49.

    CAS  PubMed  Google Scholar 

  252. Handschin C, Spiegelman BM. The role of exercise and PGC1alpha in inflammation and chronic disease. Nature. 2008;454(7203):463–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  253. Tarnopolsky MA, Rennie CD, Robertshaw HA, et al. Influence of endurance exercise training and sex on intramyocellular lipid and mitochondrial ultrastructure, substrate use, and mitochondrial enzyme activity. Am J Physiol Regul Integr Comp Physiol. 2007;292(3):R1271–8.

    CAS  PubMed  Google Scholar 

  254. Parise G, Brose AN, Tarnopolsky MA. Resistance exercise training decreases oxidative damage to DNA and increases cytochrome oxidase activity in older adults. Exp Gerontol. 2005;40(3):173–80.

    CAS  PubMed  Google Scholar 

  255. Melov S, Tarnopolsky MA, Beckman K, et al. Resistance exercise reverses aging in human skeletal muscle. PLoS One. 2007;2(5):e465.

    PubMed Central  PubMed  Google Scholar 

  256. Hakkinen K, Newton RU, Gordon SE, et al. Changes in muscle morphology, electromyographic activity, and force production characteristics during progressive strength training in young and older men. J Gerontol A Biol Sci Med Sci. 1998;53(6):B415–23.

    CAS  PubMed  Google Scholar 

  257. Visser M, Simonsick EM, Colbert LH, et al. Type and intensity of activity and risk of mobility limitation: the mediating role of muscle parameters. J Am Geriatr Soc. 2005;53(5):762–70.

    PubMed  Google Scholar 

  258. Ivey FM, Tracy BL, Lemmer JT, et al. Effects of strength training and detraining on muscle quality: age and gender comparisons. J Gerontol A Biol Sci Med Sci. 2000;55(3):B152–7 (discussion B158–9).

    CAS  PubMed  Google Scholar 

  259. Goodpaster BH, Chomentowski P, Ward BK, et al. Effects of physical activity on strength and skeletal muscle fat infiltration in older adults: a randomized controlled trial. J Appl Physiol (1985). 2008;105(5):1498–503.

    Google Scholar 

  260. Evans WJ. Effects of exercise on senescent muscle. Clin Orthop Relat Res. 2002;403 Suppl:S211–20.

    PubMed  Google Scholar 

  261. Singh MA, Ding W, Manfredi TJ, et al. Insulin-like growth factor I in skeletal muscle after weight-lifting exercise in frail elders. Am J Physiol. 1999;277(1 Pt 1):E135–43.

    CAS  PubMed  Google Scholar 

  262. Manfredi TG, Fielding RA, O’Reilly KP, et al. Plasma creatine kinase activity and exercise-induced muscle damage in older men. Med Sci Sports Exerc. 1991;23(9):1028–34.

    CAS  PubMed  Google Scholar 

  263. Villareal DT, Steger-May K, Schechtman KB, et al. Effects of exercise training on bone mineral density in frail older women and men: a randomised controlled trial. Age Ageing. 2004;33(3):309–12.

    PubMed  Google Scholar 

  264. Prats C, Donsmark M, Qvortrup K, et al. Decrease in intramuscular lipid droplets and translocation of HSL in response to muscle contraction and epinephrine. J Lipid Res. 2006;47(11):2392–9.

    CAS  PubMed  Google Scholar 

  265. Holm C, Kirchgessner TG, Svenson KL, et al. Hormone-sensitive lipase: sequence, expression, and chromosomal localization to 19 cent-q13.3. Science. 1988;241(4872):1503–6.

    CAS  PubMed  Google Scholar 

  266. Goldspink G. Cellular and molecular aspects of muscle growth, adaptation and ageing. Gerodontology. 1998;15(1):35–43.

    CAS  PubMed  Google Scholar 

  267. Visser M. Towards a definition of sarcopenia–results from epidemiologic studies. J Nutr Health Aging. 2009;13(8):713–6.

    CAS  PubMed  Google Scholar 

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Acknowledgments

The authors have no potential conflicts of interest that are directly relevant to the content of this review. No sources of funding were used to assist in the preparation of this review.

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  1. Institute of Exercise Physiology and Wellness, University of Central Florida, 4000 Central Florida Blvd, Orlando, FL, 32816, USA

    Maren S. Fragala

  2. University of Connecticut Center on Aging, University of Connecticut Health Center, Farmington, CT, USA

    Maren S. Fragala, Anne M. Kenny & George A. Kuchel

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  1. Maren S. Fragala
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Correspondence to Maren S. Fragala.

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Fragala, M.S., Kenny, A.M. & Kuchel, G.A. Muscle Quality in Aging: a Multi-Dimensional Approach to Muscle Functioning with Applications for Treatment. Sports Med 45, 641–658 (2015). https://doi.org/10.1007/s40279-015-0305-z

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