Drugs & Aging

, Volume 17, Issue 4, pp 303–316 | Cite as

Aging-Related Changes in Skeletal Muscle

Mechanisms and Interventions
  • Lars LarssonEmail author
  • Bhagavathi Ramamurthy
Review Article


The aging-related motor handicap and the growing population of elderly citizens have enormous socioeconomic effects on the modern healthcare system. The mechanisms underlying impaired motor performance in old age are complex and involve the central and peripheral nervous systems and the muscle tissue itself. It is widely accepted that the aging-related loss of muscle mass, strength and quality has a significant detrimental impact on motor performance in old age and on the ability to recover from falls, resulting in an increased risk of fractures and dependency. Therefore, the prevention of falls and gait instability is a very important safety issue, and different intervention strategies have been used to improve motor performance among the aging population. There is general consensus that physical exercise is a powerful intervention to obtain long term benefits on muscle function, reduce the frequency of falls, and to maintain independence and a high quality of life in older persons. The results from studies using different types of hormone supplementation therapies have shown interesting and encouraging effects on skeletal muscle mass and function. However, the potential risks with both growth hormone and androgen treatment are not known and long term clinical trials are needed to address safety concerns and the effects on skeletal muscle.

Recent advancements in cellular/molecular, physiological and molecular biological techniques will significantly facilitate our understanding of aging-related impairments of muscle function and contribute to the evaluation of different intervention strategies.


Caloric Restriction Myofibrillar Protein Motility Assay Specific Tension Hind Limb Suspension 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This study was supported by grants from the Swedish Medical Research Council (8651), the European Union Commission (Biomed-2), the Swedish Work Environment Fund, the Swedish Central Association for Promotion of Sport, the Osterman Foundation and the Gerontology Center, the Pennsylvania State University, University Park, USA.


  1. 1.
    Frontera WR, Meredith CN. Exercise in the rehabilitation of the elderly. In: Felsenthal G, Garrison SJ, Steinberg FU, editors. Rehabilitation of the aging and elderly patient. Baltimore (MD): Williams & Wilkins, 1993: 35–46Google Scholar
  2. 2.
    Hughes MA, Myers BS, Schenkman ML. The role of strength in rising from a chair in the functionally impaired elderly. J Biomech 1996 29: 1509–13PubMedGoogle Scholar
  3. 3.
    Hemenway D, Solnick SJ, Koeck C, et al. The incidence of stairway injuries in Austria. Accid Anal Prev 1994; 26: 675–9PubMedCrossRefGoogle Scholar
  4. 4.
    Suzuki M, Okamura T, Shimazu Y, et al. A study of falls experience by institutionalized elderly. Jpn J Pub Health 1992 39: 927–40Google Scholar
  5. 5.
    Svantröm L. Falls on stairs: an epidemiological study. Lund, Sweden: Department of Social and Preventive Medicine and Architecture, Lund Institute of Technology, 1973Google Scholar
  6. 6.
    LaCroix AZ, Guralnik JM, Berkman LF, et al. Maintaining mobility in late life. II. Smoking, alcohol consumtion, physical activity, and body mass index. Am J Epidemiol 1993 137: 858–69PubMedGoogle Scholar
  7. 7.
    Moffet H, Richards CL, Malouin F, et al. Impact of knee extensor strength deficits on stair ascent performance in patients after medical meniscectomy. Scand J Rehabil Med 1993; 25: 63–71PubMedGoogle Scholar
  8. 8.
    Rantanen T, Era P, Heikkinen E. Maximal isometric strength and mobility among 75-year-old men and women. Age Ageing 1994; 23: 132–7PubMedCrossRefGoogle Scholar
  9. 9.
    Shiomi T. Effects of different patterns of stairclimbing on physiological cost and motor efficiency. J Human Ergol (Tokyo) 1994; 23: 111–20Google Scholar
  10. 10.
    Andriacchi TP, Andersson GBJ, Fermier RW, et al. A study of lower-limb mechanics during stair-climbing. J Bone Joint Surg 1980; 62: 749–57PubMedGoogle Scholar
  11. 11.
    Costigan PA, Wyss UP, Deluzio KJ, et al. Semiautomatic three dimensional knee motion assessment system. Med Biol Eng Comput 1992; 30: 343–50PubMedCrossRefGoogle Scholar
  12. 12.
    Jevsevar DS, Riley PO, Hodge WA, et al. Knee kinematics and kinetics during locomotor activities of daily living in subjects with arthroplasty and in healthy control subjects. Phys Ther 1993; 73: 229–39PubMedGoogle Scholar
  13. 13.
    Livingston LA, Stevenson JM, Olney SJ. Stairclimbing kinematics on stairs of different dimensions. Arch Phys Med Rehab 1991; 72: 398–402Google Scholar
  14. 14.
    McFayden BJ, Winter DA. An integrated biomechanical analysis of normal stair ascent and descent. J Biomech 1988; 21: 733–44CrossRefGoogle Scholar
  15. 15.
    Nevitt MC, Cummings SR, Hues ES. Risk factors for injurious falls: a prospective study. J Gerontol 1991; 46: 164–70CrossRefGoogle Scholar
  16. 16.
    Schultz AB, Ashton-Miller JA, Alexander NB. What leads to age and gender differences in balance maintenance and recovery? Muscle Nerve Suppl 1997; 5: S60–4PubMedCrossRefGoogle Scholar
  17. 17.
    Ansved T, Larsson L. Histochemical properties of aging rat skeletal muscle. In: Mohr U, Dungworth DL, Capen CC, editors. Pathobiology of the aging rat. Vol. 2. Washington, DC: ILSI Press, 1994:521–34Google Scholar
  18. 18.
    Brooks SV, Faulkner JA. The magnitude of the initial injury induced by stretches of maximally activated muscle fibres of mice and rats increases in old age. J Physiol 1996; 497: 573–80PubMedGoogle Scholar
  19. 19.
    Devor ST, Faulkner JA. Regeneration of new fibers in muscles of old rats reduces contraction-induced injury. J Appl Physiol 1999; 87: 750–6PubMedGoogle Scholar
  20. 20.
    Faulkner JA, Brooks SV, Zerba E. Muscle atrophy and weakness with aging: contraction-induced injury as an underlying mechanism. J Gerontol ABiol Sci Ned Sci 1995; 50: 124–9Google Scholar
  21. 21.
    Larsson L, Ansved T. Effects of ageing on the motor unit. Prog Neurobiol 1995; 45: 397–458PubMedCrossRefGoogle Scholar
  22. 22.
    Quetelet A. Sur l’homme et le dévelopment de ses facultés. Brussels: Haumann, 1836Google Scholar
  23. 23.
    Bassey EJ, Bendall JC, Short AH. Muscle strength in triceps surae and objectively measured customary walking activity in men and women over 65 years of age. Clin Sci 1988; 74: 85–9PubMedGoogle Scholar
  24. 24.
    Bruce SA, Newton D, Woledge RC. Effect of subnutrition on normalized muscle force and relaxation rate in human subjects using voluntary contractions. Clin Sci 1989; 76: 637–41PubMedGoogle Scholar
  25. 25.
    Cohn SH, Vartsky D, Yasumura S, et al. Compartmental body composition based on total-body, potassium, and calcium. Am J Physiol 1980; 239: E524–30PubMedGoogle Scholar
  26. 26.
    Cunningham DA, Morrison D, Rice CL, et al. Ageing and isokinetic plantar force. Eur J Appl Physiol 1987; 56: 24–9CrossRefGoogle Scholar
  27. 27.
    Fiatarone MA, ONeill EF, Ryan ND, et al. Exercise training and nutritional supplementation for phy sical frailty in very elderly people. N Engl J Med 1994; 330: 1769–75PubMedCrossRefGoogle Scholar
  28. 28.
    Frontera WR, Hughes VA, Lutz KS, et al. A cross-sectional study of muscle mass and strength in 45- to 78-year-old men and women. J Appl Physiol 1991; 71: 644–50PubMedGoogle Scholar
  29. 29.
    Häkkinen K, Izquierdo M, Aguado X, et al. Isometric and dynamic explosive force production of leg extensor muscles in men at different ages. J Hum Mov Stud 1996; 31: 105–21Google Scholar
  30. 30.
    Häkkinen K, Kallinen M, Linnamo V, et al. Neuromuscular adaptations during bilateral versus unilateral strength training in middle-aged and elderly men and women. Acta Physiol Scand 1996; 158: 77–88PubMedCrossRefGoogle Scholar
  31. 31.
    Häkkinen K, Kraemer WJ, Kallinen M, et al. Bilateral and unilateral neuromuscular function and muscle cross-sectional area in middle-aged and elderly men and women. J Gerontol Biol Sci 1996; 51A: B21–9CrossRefGoogle Scholar
  32. 32.
    Larsson L, Grimby G, Karlsson J. Muscle strength and speed of movement in relation to age and muscle morphology. J Appl Physiol 1979; 46: 451–56PubMedGoogle Scholar
  33. 33.
    Novak LP. Aging, total body potassium, fat free-mass, and cell mass in males and females between ages 18 and 85 years. J Gerontol 1972; 27: 438–43PubMedCrossRefGoogle Scholar
  34. 34.
    Rice CL, Cunningham DA, Paterson DH, et al. Strength in an elderly population. Arch Phys Med Rehab 1984; 70: 391–7Google Scholar
  35. 35.
    Young A, Stokes M, Crowe M. The size and strength of the quadriceps muscle of old and young women. Eur J Clin Invest 1984; 14: 282–7PubMedCrossRefGoogle Scholar
  36. 36.
    Alnaqeeb MA, Al Zaid NS, Goldspink G. Connective tissue changes properties of developing and aging skeletal muscle. JAnat 1984; 139:677–89Google Scholar
  37. 37.
    Ansved T, Larsson L. The effects of age on contractile, mor phometrical and enzyme-histochemical properties of the rat soleus muscle. J Neurol Sci 1989; 93: 105–24PubMedCrossRefGoogle Scholar
  38. 38.
    Fujisawa K. Some observations on the skeletal musculature of aged rats. Part 1. Histological aspects. J Neurol Sci 1974; 22: 353–66PubMedCrossRefGoogle Scholar
  39. 39.
    Kovanen V, Suominen H, Peltonen L. Effects of aging and life long physical training on collagen in slow and fast skeletal muscle in rats. Cell Tissue Res 1987; 248: 247–55PubMedCrossRefGoogle Scholar
  40. 40.
    Larsson L, Edström L. Effects of age on enzyme-histochemical fibre spectra and contractile properties of fast- and slow-twitch skeletal muscles in the rat. J Neurol Sci 1986; 76: 69–89PubMedCrossRefGoogle Scholar
  41. 41.
    Mohan S, Radha E. Age-related changes in rat muscle collagen. Gerontology 1980; 26: 61–7PubMedCrossRefGoogle Scholar
  42. 42.
    Frantzell A, Ingelmark BE. Occurence and distribution of fat in human muscles at various age levels. Acta Soc Med Upsalien 1951; 56: 59–87Google Scholar
  43. 43.
    Inamura KH, Ashida H, Ishikawa T, et al. Human major psoas muscle and sacrospinalis muscle in relation to age: a study by computed tomography. J Gerontol 1983; 38: 678–81CrossRefGoogle Scholar
  44. 44.
    Larsson L. Ageing in mammalian skeletal muscles. In: Mortimer JA, Pirozzolo FJ, Maletta GJ, editors. The aging motor system: advances in neurogerontology. Vol 3. New York: Praeger, 1982: 60–97Google Scholar
  45. 45.
    Hill AV The dimensions of animals and their muscular dynamics. Sci Prog 1950; 38: 209–30Google Scholar
  46. 46.
    Hoffman PA, Greaser ML, Moss RL. C-protein limits shortening velocity of rabbit skeletal muscle fibres at low levels of Ca2+activation. J Physiol 1991; 439: 701–15Google Scholar
  47. 47.
    Hoffman PA, Hartzell HC, Moss RL. Alterations in Ca2+ sensitive tension due to partial extraction of C-protein from rat skinned cardiac myocytes and rabbit skeletal muscle fibers. J Gen Physiol 1991; 971: 141–63Google Scholar
  48. 48.
    Delbono O, O’Rourke KS, Ettinger WH. Excitation-calcium release uncoupling in aged single human skeletal muscle fibers. J Membr Biol 1995; 148: 211–22PubMedGoogle Scholar
  49. 49.
    Delbono O, Renganathan M, Messi ML. Excitation-Ca2+ release-contraction coupling in single aged human skeletal muscle fiber. Muscle Nerve Suppl 1997; 5: 5: S88–92PubMedCrossRefGoogle Scholar
  50. 50.
    Larsson L, Moss RL. Maximal velocity of shortening in relation to myosin isoform composition in single fibres from human skeletal muscles. J Physiol 1993; 472: 595–614PubMedGoogle Scholar
  51. 51.
    Fitts RH, Costill DL, Gardetto PR. Effects of swim exercise training on human muscle fiber function. J Appl Physiol 1989; 66: 465–75PubMedGoogle Scholar
  52. 52.
    Larsson L. A technique for measuring contractile properties in single chemically skinned human fibres obtained from percutaneous biopsies. J Neurol Sci 1990; 98 Suppl: 430Google Scholar
  53. 53.
    Larsson L, Li X, Frontera WR. Effects of ageing on shortening velocity and myosin isoform composition in single fibres from man. Am J Physiol 1997; 272: C638–49PubMedGoogle Scholar
  54. 54.
    Larsson L, Li X, Berg H, et al. Effects of removal of weight-bearing function on contractility and myosin isoform composition in single human skeletal muscle cells. Pflüg Arch 1996; 432: 320–8CrossRefGoogle Scholar
  55. 55.
    Larsson L, Salviati G. A technique for studies of the contractile apparatus in single human muscle fibre segments obtained by percutaneous biopsy. Acta Physiol Scand 1992; 146: 485–95PubMedCrossRefGoogle Scholar
  56. 56.
    Stienen GJM, Kiers JL, Bottinelli R, et al. Myofibrillar ATPase activity in skinned human skeletal muscle fibres: fibre type and temperature dependence. J Physiol 1996; 493: 299–307PubMedGoogle Scholar
  57. 57.
    Frontera WR, Grimby L, Larsson L. Motoneurone firing rates, contractility and myosin isoform composition in single muscle fibres from patients with central paresis. Muscle Nerve 1997; 20: 938–47PubMedCrossRefGoogle Scholar
  58. 58.
    Lankford EB, Epstein ND, Fananapazir L, et al. Abnormal con tractile properties of muscle fibers expressing β-myosin heavy chain gene mutations in patients with hypertrophie cardiomyopathy. J Clin Invest 1995; 95: 1409–14PubMedCrossRefGoogle Scholar
  59. 59.
    Larsson L, Roland A. Farmakautlöst tetrapares orsakad av my-osinförlusthos en intensivvårdspatient. Läkartidningen 1996; 23: 2249–54Google Scholar
  60. 60.
    Larsson L, Müller U, Li X, et al. Thyroid hormone regulation of myosin heavy chain isoform composition in young and old rats: with special reference to type IIX myosin. Acta Physiol Scand 1995; 153: 109–16PubMedCrossRefGoogle Scholar
  61. 61.
    Larsson L, Li X, Edström L, et al. Loss of muscle myosin and acute quadriplegia in patients treated with with non-depolarizing neuromuscular blocking agents and corticosteroids: underlying cellular and molecular mechanisms. Crit Care Med 2000; 28: 34–45PubMedCrossRefGoogle Scholar
  62. 62.
    Close R. The relation between intrinsic speed of shortening and duration of the active state of muscle. J Physiol 1965; 180: 542–59PubMedGoogle Scholar
  63. 63.
    McMahon TA. Muscles, reflexes, and locomotion. New Jersey: Princeton University Press, 1984Google Scholar
  64. 64.
    Rome LC, Sosnicki AA, Goble DO. Maximum velocity of shortening of three fibre types from horse soleus muscle: implications for scaling with body size. J Physiol 1990; 431: 173–85PubMedGoogle Scholar
  65. 65.
    Moss RL, Diffee GM, Greaser ML. Contractile properties of skeletal muscle fibres in relation to myofibrillar protein iso-forms. Rev Physiol Bioch Pharm 1995; 126: 1–63CrossRefGoogle Scholar
  66. 66.
    Bottinelli R, Betto R, Schiaffino S, et al. Unloaded shortening velocity and myosin heavy chain and alkali light chain iso-form composition in rat skeletal muscle fibres. J Physiol 1994; 478: 341–49PubMedGoogle Scholar
  67. 67.
    Greaser ML, Moss RL, Reiser PJ. Variations in contractile properties of rabbit single muscle fibers in relation to troponin T isoforms and myosin light chains. J Physiol 1988; 409: 85–98Google Scholar
  68. 68.
    Li X, Larsson L. Maximum shortening velocity and myosin isoforms in single fibers from young and old rats. Am J Physiol 1996; 270: C352–60PubMedGoogle Scholar
  69. 69.
    Sweeney HL, Kushmerick MJ, Mabuchi K, et al. Myosin alkali light chain and heavy chain variations correlate with altered shortening velocity of isolated muscle fibers. J Biol Chem 1988; 263: 9034–9PubMedGoogle Scholar
  70. 70.
    Lowey S, Waller GS, Trybus KM. Function of skeletal muscle myosin heavy and light chain isoforms by an in vitro motility assay. J Biol Chem 1993; 268: 20414–8PubMedGoogle Scholar
  71. 71.
    Degens H, Yu F, Li X, et al. Effects of age and gender on short ening velocity and expression of myosin isoforms in single rat muscle fibres. Acta Physiol Scand 1998; 163: 33–40PubMedCrossRefGoogle Scholar
  72. 72.
    Li X, Larsson L. Contractility and myosin isoform compositions of skeletal muscles and muscle cells from rats treated with thyroid hormone for 0,4 and 8 weeks. J Muscle Res Cell Motil 1997; 18: 1–10CrossRefGoogle Scholar
  73. 73.
    Thompson LV, Brown M. Age-related changes in contractile properties of single skeletal muscle fibers from the soleus muscle. J Appl Physiol 1999; 86: 881–6PubMedCrossRefGoogle Scholar
  74. 74.
    Yu F, Degens H, Li X, et al. Effects of thyroid hormone, gender and age on contractility and myosin composition in single rat soleus fibres. Pflüg Arch 1998; 437: 21–30CrossRefGoogle Scholar
  75. 75.
    Galler S, Hilber K, Gohlsch B, et al. Two functionally distinct myosin heavy chain isoforms in slow skeletal muscle fibres. FEBS Lett 1997; 410: 150–2PubMedCrossRefGoogle Scholar
  76. 76.
    Hämäläinen N, Pette D. Expression of an α-cardiac-like myosin heavy chain in diaphragm, chronically stimulated, and denervated fast-twitch muscle of rabbit. J Muscle Res Cell Motil 1997; 18:401–11PubMedCrossRefGoogle Scholar
  77. 77.
    Hughes SH, Cho M, Karsch-Mizrachi I, et al. Three slow myosin heavy chains sequentially expressed in developing mammalian skeletal muscle. Dev Biol 1993; 158: 183–99PubMedCrossRefGoogle Scholar
  78. 78.
    Jandreski MA, Sole MJ, Liew CC. Two different forms of beta myosin heavy chain are expressed in human striated muscle. Hum Genet 1987; 77: 127–31PubMedCrossRefGoogle Scholar
  79. 79.
    Fauteck SP, Kandarian SC. Sensitive detection of myosin heavy chain composition in skeletal muscle under different loading conditions. Am J Physiol 1995; 268: C419–24PubMedGoogle Scholar
  80. 80.
    Schiaffino S, Reggiani C. Molecular diversity of myofibrillar proteins: gene regulation and functional significance. Physiol Rev 1996; 76: 371–423PubMedGoogle Scholar
  81. 81.
    Hoh JFY Muscle fiber types and function. Curr Opin Rheum 1992; 4: 801–8Google Scholar
  82. 82.
    Smerdu V, Karsch-Mizrachi I, Campione M, et al. Type IIx myosin heavy chain transcripts are expressed in type IIb fibers of human skeletal muscle. Am J Physiol 1994; 36: C1723–8Google Scholar
  83. 83.
    Pette D, Staron RS. Cellular and molecular diversities of mammalian skeletal muscle fibers. Rev Physiol Biochem Pharm 1990; 116: 1–76Google Scholar
  84. 84.
    Robbins J, Horan T, Gulick J, et al. The chicken myosin heavy chain family. J Biol Chem 1986; 261: 6606–12PubMedGoogle Scholar
  85. 85.
    Rattan SIS. Synthesis, modifications, and turnover of proteins during aging. Exp Gerontol 1996; 31: 33–47PubMedCrossRefGoogle Scholar
  86. 86.
    Balagopal P, Rooyackers OE, Asey 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: E790–800PubMedGoogle Scholar
  87. 87.
    Mooradian AD, Wong NCW. Molecular biology of aging: part II. A synopsis of current research. J Am Geriatr Soc 1991; 39: 717–23PubMedGoogle Scholar
  88. 88.
    Pryor WA, Cueto R, Jin X, et al. A practical method for preparing peroxynitrite solutions of low ionic strength and free of hydrogen peroxide. Free Radic Biol Med 1995; 18: 75–83PubMedCrossRefGoogle Scholar
  89. 89.
    Reid MB, Khawli F, Moody M. Reactive oxygen in skeletal muscle III. Contractility of unfatigued muscle. J Appl Physiol 1993; 75: 1081–7PubMedGoogle Scholar
  90. 90.
    Kobzik L, Reid MB, Bredt DS, et al. Nitric oxide in skeletal muscle. Nature 1994; 372: 546–8PubMedCrossRefGoogle Scholar
  91. 91.
    Viner RI, Ferrington DA, Hühmer AFR, et al. Accumulation of nitrotyrosine on the SERCA2a isoform of SR Ca-ATPase of rat skeletal muscle during aging: a peroxynitrite-mediated process? FEBS Lett 1996; 379: 286–90PubMedCrossRefGoogle Scholar
  92. 92.
    Wink DA, Nims RW, Darbyshire JF. Reaction kinetics for nitrosation of cysteine and glutathione in aerobic nitric oxide solutions at neutral pH: insight into the fate and physiological effects of intermediates generated in the NO/O2 reaction. Chem Res Toxicol 1994; 7: 519–25PubMedCrossRefGoogle Scholar
  93. 93.
    Warshaw DM. The in vitro motility assay: a window into the myosin molecular motor. News Physiol Sci 1996; 11: 1–7Google Scholar
  94. 94.
    Homsher E, Wang F, Sellers JR. Factors affecting movement of F-actin filaments propelled by skeletal muscle meromyosin. Am J Physiol 1992; 262: C714–23PubMedGoogle Scholar
  95. 95.
    Kron SJ, Spudich JA. Fluorescent actin filaments move on myosin fixed to a glass surface. Proc Natl Acad Sci U S A 1986; 83: 6272–6PubMedCrossRefGoogle Scholar
  96. 96.
    Van Buren P, Work SS, Warshaw DM. Enhanced force generation by smooth muscle myosin in vitro. Proc Natl Acad Sci U S A 1994; 91:202–5CrossRefGoogle Scholar
  97. 97.
    Finer JT, Simmons RM, Spudich JA. Single myosin molecule mechanics: piconewton forces and nanometre steps. Nature 1994; 368: 113–9PubMedCrossRefGoogle Scholar
  98. 98.
    Höök P, Li X, Larsson L. Effects of aging on in vitro motility speed of β/slow myosin extracted from single muscle cells. FASEB J 1998; 12: 2430Google Scholar
  99. 99.
    Höök P, Li X, Sleep J, et al. Motility of slow myosin extracted from single muscle cells in young and old rat soleus muscle. JPhysiol 1999 520:463–71CrossRefGoogle Scholar
  100. 100.
    Avigad G, Kniep A, Bailin G. Reaction of rabbit skeletal myosin with D glucose 6-phosphate. Biochem Mol Biol Int 1996; 40: 273–84PubMedGoogle Scholar
  101. 101.
    Watanabe H, Ogasawara M, Suzuki N, et al. Glycation of myofibrillar protein in aged rats and mice. Biosci Biotech Biochem 1992; 56: 1109–12CrossRefGoogle Scholar
  102. 102.
    Brownlee M. Advanced protein glycosylation in diabetes and aging. Am Rev Med 1995; 46: 223–34CrossRefGoogle Scholar
  103. 103.
    Ramamurthy B, Höök P, Larsson L. An overview of carbohydrate-protein intercations with specific reference to myosin and ageing. Acta Physiol Scand 1999; 167: 327–9PubMedCrossRefGoogle Scholar
  104. 104.
    Goldspink G, Scutt A, Loughna PT, et al. Gene expression in skeletal muscle in response to stretch and force generation. Am J Physiol 1991; 262: R356–63Google Scholar
  105. 105.
    Goldspink G. Changes in muscle mass and phenotype and the expression of autocrine and systemic growth factors by muscle in response to stretch and overload. J Anat 1999; 194: 323–34PubMedCrossRefGoogle Scholar
  106. 106.
    Aniansson A, Gustavsson E. Physical training in elderly men with specific reference to quadriceps muscle strength and morphology. Clin Physiol 1981; 1: 87–98CrossRefGoogle Scholar
  107. 107.
    Evans WJ. Reversing sarcopenia: how weight traning can build strength and vitality. Geriatrics 1996; 51: 46–53PubMedGoogle Scholar
  108. 108.
    Fiatarone MA, Marks EC, Ryan ND, et al. High-intensity strength training in nonagenarians. JAMA 1990; 263: 3029–34PubMedCrossRefGoogle Scholar
  109. 109.
    Frontera WR, Meredith CN, O’Reilly KP, et al. Strength conditioning in older men: skeletal muscle hypertrophy and improved function. J Appl Physiol 1988; 64: 1038–44PubMedGoogle Scholar
  110. 110.
    Larsson L. Physical training effects on muscle morphology in sedentary males. Med Sci Sports Exerc 1982; 14: 203–6PubMedGoogle Scholar
  111. 111.
    Bassey EJ, Fiatarone MA, O’Neill EF, et al. Leg extensor power and functional performance in very old men and women. Clin Sci 1992; 82: 321–7PubMedGoogle Scholar
  112. 112.
    Booth FW, Criswell DS. Molecular events underlying skeletal muscle atrophy and the development of effective counter-measures. Int J Sports Med 1997; 18Suppl. 4: S265–9PubMedCrossRefGoogle Scholar
  113. 113.
    Dudley GA, Duvoisin MR, Convertino VA, et al. Alterations of the in vivo torque-velocity relationship of human skeletal muscle following 30 days exposure to simulated microgravity. Aviat Space Envir Med 1989; 60: 659–63Google Scholar
  114. 114.
    Edgerton VR, Zhou M-Y, Ohira Y, et al. Human fiber size and enzymatic properties after 5 and 11 days of spaceflight. J Appl Physiol 1995; 78: 1733–9PubMedGoogle Scholar
  115. 115.
    Berg HE, Dudley GA, Häggmark T, et al. Effects of lower limb unloading on skeletal muscle mass and function in humans. J Appl Physiol 1991; 70: 1882–5PubMedCrossRefGoogle Scholar
  116. 116.
    Reiser PJ, Kasper CE, Moss RL. Myosin subunits and contractile properties of single fibers from hypokinetic rat muscles. J Appl Physiol 1987; 63: 2293–300PubMedGoogle Scholar
  117. 117.
    Gardetto PR, Schlüter JM, Fitts RH. Contractile function of single muscle fibers after hindlimb suspension. J Appl Physiol 1989; 66: 2739–49PubMedGoogle Scholar
  118. 118.
    Booth FW, Kirby CR. Changes in skeletal muscle gene expression consequent to altered weight bearing. Am J Physiol 1992; 262: R329–32PubMedGoogle Scholar
  119. 119.
    Thomason DB, Booth FW. Atrophy of the soleus muscle by hindlimb unweighting. J Appl Physiol 1990; 68: 1–12PubMedCrossRefGoogle Scholar
  120. 120.
    Welle S, Thornton R, Jozefowicz R, et al. Myofibrillar protein synthesis in young and old men. Am J Physiol 1993; 264: E693–8PubMedGoogle Scholar
  121. 121.
    Yarasheski KE, Zachwieja JJ, Bier DM. Acute effects of resistance exercise on muscle protein synthesis rate in young and elderly men and women. Am J Physiol 1993; 265: E210–14PubMedGoogle Scholar
  122. 122.
    Yarasheski KE, Zachwieja JJ, Campbell JA, et al. Effect of growth hormone and resistance exercise on muscle growth and strength in older men. Am J Physiol 1995 268: E268–76PubMedGoogle Scholar
  123. 123.
    Hack V, Schmid D, Breitkreutz R, et al. Cystine levels, cystine flux, and protein catabolism in cancer cachexia, HIV/SIV infection, and senescence. FASEB J 1997; 11: 84–92PubMedGoogle Scholar
  124. 124.
    Phillips SK, Rook KM, Siddle NC, et al. Muscle weakness in women occurs at an earlier age than in men, but strength is preserved by hormone replacement therapy. Clin Sci 1993; 84: 95–8PubMedGoogle Scholar
  125. 125.
    Armstrong AL, Oborne J, Coupland CA, et al. Effects of hormone replacement therapy on muscle performance and balance in post-menopausal women. Clin Sci 1996; 91: 685–90PubMedGoogle Scholar
  126. 126.
    Brown M, Birge SJ, Kohrt WM. Hormone replacement therapy does not augment gains in muscle strength or fat-free mass in response to weight-bearing exercise. J Gerontol A Biol Sci Med Sci 1997; 52: B166–70PubMedCrossRefGoogle Scholar
  127. 127.
    Preisinger E, Alacamlioglu Y, Saradeth T, et al. Forearm bone density and grip strength in women after menopause, with and without estrogen replacement therapy. Maturitas 1995; 21: 57–63PubMedCrossRefGoogle Scholar
  128. 128.
    Seeley DG, Cauley JA, Grady D, et al. Is postmenopausal estrogen therapy associated with neuromuscular function or falling in elderly women? Study of osteoporotic fractures research group. Arch Intern Med 1995; 155: 293–9PubMedCrossRefGoogle Scholar
  129. 129.
    Morley JE, Kaiser FE, Sih R, et al. Testosterone and frailty. Clin Geriatr Med 1997; 13: 685–695PubMedGoogle Scholar
  130. 130.
    Tenover JL. Testosterone and the aging male. J Androl 1997;18: 103–6PubMedGoogle Scholar
  131. 131.
    Tenover JS. Effects of testosterone supplementation in the aging male. J Clin Endocr Metab 1992; 75: 1092–8PubMedCrossRefGoogle Scholar
  132. 132.
    Urban RJ, Bodenburg YH, Gilkison C, et al. Testosterone administration to elderly men increases skeletal muscle strength and protein synthesis. Am J Physiol 1995; 269: E820–6PubMedGoogle Scholar
  133. 133.
    McKoy G, Ashley W, Mander J, et al. Expression of insulin growth factor-1 splice variants and structural genes in rabbit skeletal muscle induced by stretch and stimulation. J Physiol 1999; 516: 583–92PubMedCrossRefGoogle Scholar
  134. 134.
    Florini JR, Prinz PN, Vitiello MV, et al. Somatomedin-C levels in healthy young and old men: relationship to peak and 24-hour integrated levels of growth hormone. J Gerontol 1985; 40: 2–7PubMedCrossRefGoogle Scholar
  135. 135.
    Capuano-Pucci D, Rheault W, Rudman D. Relationship between plasma somatomedin C and muscle performance in a geriatric male population. Am J Phys Med 1987; 66: 364–70PubMedGoogle Scholar
  136. 136.
    Rudman D. Growth hormone, body composition and aging. J Am Geriatr Soc 1985; 33: 800–7PubMedGoogle Scholar
  137. 137.
    Vittone J, Blackman MR, Busby-Whitehead J, et al. Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men. Metabolism 1997; 46: 89–96PubMedCrossRefGoogle Scholar
  138. 138.
    Sonntag WE, Steger RW, Forman LJ, et al. Decreased pulsatile release of growth hormone in old male rats. Endocrinology 1980; 107: 1875–9PubMedCrossRefGoogle Scholar
  139. 139.
    Beach RK, Kostyo JL. Effect of growth hormone on the DNA content of muscle of young hypophysectomized rats. Endocrinology 1968; 82: 882–8PubMedCrossRefGoogle Scholar
  140. 140.
    Flain KE, Li JB, Jefferson LS. Protein turnover in rat skeletal muscle: effects of hypophysectomy andgrowth hormone. Am J Physiol 1978; 234: E38–43Google Scholar
  141. 141.
    Sonntag WE, Hykla VW, Meites J. Growth hormone restores protein synthesis in skeletal muscles of old male rats. J Gerontol 1984; 40: 689–94CrossRefGoogle Scholar
  142. 142.
    DeLuca A, Pierno S, Cocchi D, et al. Growth hormone administration to aged rats improves membrane electrical properties of skeletal muscle fibers. J Pharmacol Exp Ther 1994; 269: 948–53Google Scholar
  143. 143.
    Jorgenesen JE, Pedersen SA, Thuesen L, et al. Beneficial effects of growth hormone treatment in GH-deficient adults. Lancet 1989; I: 1221–5CrossRefGoogle Scholar
  144. 144.
    Marcus R, Butterfield G, Holloway L, et al. Effects of short term administration of recombinant human growth hormone to elderly people. J Clin Endocrinol Metab 1990; 70: 519–27PubMedCrossRefGoogle Scholar
  145. 145.
    Rudman D, Feller AG, Nagraj HS, et al. Effects of human growth hormone in men over 60 years old. N Engl J Med 1990; 323: 1–6PubMedCrossRefGoogle Scholar
  146. 146.
    Welle S, Thornton R, Statt M, et al. Growth hormone increases muscle mass and strength but does not rejuvenate myofibrillar protein synthesis in healthy subjects over 60 years old. J Clin Endocr Metab 1996; 81: 3239–43PubMedCrossRefGoogle Scholar
  147. 147.
    Florini JR, Ewton DZ, Coolican SA. Growth hormone and the insulin-like growth factor system in myogenesis. Endocr Rev 1996; 17:481–517PubMedGoogle Scholar
  148. 148.
    Barton-Davis ER, Shoturma DI, Musaro A, et al. Viral mediated expression of IGF-I blocks the aging-related loss of skeletal muscle function. Proc Natl Acad Sci U S A 1998; 95: 15603–7PubMedCrossRefGoogle Scholar
  149. 149.
    Barton-Davis ER, Shoturma DI, Sweeney HL. Contribution of satellite cells to IGF-I induced hypertrophy of skeletal muscle. Acta Physiol Scand 1999; 167: 301–5PubMedCrossRefGoogle Scholar
  150. 150.
    Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol A Biol Sci Med Sci 1956; 11:298–300Google Scholar
  151. 151.
    Benzi G, Pastoris O, Marzatico F, et al. The mitochondrial electron transfer alteration as a factor involved in brain aging. Neuronal Aging 1992; 13: 361–8CrossRefGoogle Scholar
  152. 152.
    Ji LL. Antioxidant enzyme response to exercise and aging. Med Sci Sports Exerc 1993; 25: 225–31PubMedGoogle Scholar
  153. 153.
    Bejma J, Ji LL. Aging and acute exercise enhance free radical generation in rat skeletal muscle. J Appl Physiol 1999; 87: 465–70PubMedGoogle Scholar
  154. 154.
    Pansarasa O, Bertorelli L, Vecchiet J, et al. Age-dependent changes of antioxidant activities and markers of free radical damage in human skeletal muscle. Free Radic Biol Med 1999; 27: 617–22PubMedCrossRefGoogle Scholar
  155. 155.
    Orr WC, Sohal RS. Extension of life span by overexpression of Superoxide dismutase and catalase in Drosophila melanogaster. Science 1994; 263: 1128–30PubMedCrossRefGoogle Scholar
  156. 156.
    Ho YS, Magnanat JL, Bronson RT, et al. Mice deficient in cellular glutathione peroxidase develop normally and show no increased sensitivity to hyperoxia. J Biol Chem 1997; 272: 16644–51PubMedCrossRefGoogle Scholar
  157. 157.
    Ji LL, Leeuwenburgh C, Leichtweis S, et al. Oxidative stress and aging: role of exercise and its influences on antioxidant systems. Ann NY Acad Sci 1998; 854: 102–17PubMedCrossRefGoogle Scholar
  158. 158.
    Oh-Ishi S, Kizaki T, Yamashita H, et al. Alterations of Superoxide dismutase iso-enzyme activity, content and mRNA expression with aging in rat skeletal muscle. Mech Ageing Dev 1995; 84: 65–76PubMedCrossRefGoogle Scholar
  159. 159.
    Leeuwenburgh C, Feibig R, Chandwaney R, Ji LL. Aging and exercise training in skeletal muscle: responses of glutathione and antioxidant enzyme systems. Am JPhysiol 1994 Aug 267 (2 Pt 2): R439–45Google Scholar
  160. 160.
    Asayama K, Dobashi K, Hayashibe H, et al. Vitamin E protects against thyroxine-induced acceleration of lipid peroxidation in cardiac and skeletal muscles in rats. J Nutr Sci Vitaminol (Tokyo) 1989 Oct; 35(5): 407–18CrossRefGoogle Scholar
  161. 161.
    Goldfarb AH, Mclntosh MK, Boyer BT, et al. Vitamin E effects on indexes of lipid peroxidation in muscle from DHEA treated and exercised rats. J Appl Physiol 1994 Apr; 76(4): 1630–5PubMedGoogle Scholar
  162. 162.
    Persky AM, Green PS, Stubley L, et al. Protective effect of estrogens against oxidative damage to heart and skeletal muscle in vivo and in vitro. Proc Soc Exp Biol Med 2000; 223: 59–66PubMedCrossRefGoogle Scholar
  163. 163.
    Weinruch R, Walford RL. Dietary restriction on mice beginning at 1 year of age: effect on life-span and spontaneous cancer incidence. Science 1982; 215: 1415–8CrossRefGoogle Scholar
  164. 164.
    Lee CK, Klopp RG, Weindruch R, et al. Gene expression profile of aging and its reterdation by caloric restriction. Science 1999; 285: 1390–3PubMedCrossRefGoogle Scholar
  165. 165.
    Renganathan M, Delbono O. Caloric restriction prevents age-related decline in skeletal muscle dihydropyridine receptor and ryanodine receptor expression. FEBS Lett 1998; 434: 346–50PubMedCrossRefGoogle Scholar
  166. 166.
    Weinruch R, Cheung MK, Verity A, et al. Modifications of mitochondrial respiration by aging and dietary restriction. Mech Ageing Dev 1980; 12: 375–92CrossRefGoogle Scholar
  167. 167.
    Sohal RS, Weinruch R. Oxidative stress, caloric restriction and aging. Science 1996; 273: 59–63PubMedCrossRefGoogle Scholar
  168. 168.
    Sohal RS, Agarwal S, Sohal BH. Oxidative stress and aging in the Mongolian gerbil (Meriones unguiculatus). Mech Ageing Dev 1995; 81: 15–25PubMedCrossRefGoogle Scholar
  169. 169.
    Clayton DA. Transcription of the mammalian mitochondrial genome. Ann Rev Biochem 1984; 53: 573–94PubMedCrossRefGoogle Scholar
  170. 170.
    Cadenas E, Packer L, editors. Understanding the process of aging: the roles of mitochondria, free radicals, and antioxidants. New York: Marcel Dekker, Inc., 1999Google Scholar
  171. 171.
    Richmonds CR, Kaminski HJ. Nitric oxide myotoxicity is age related. Mech Ageing Dev 2000; 113: 183–91PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2000

Authors and Affiliations

  1. 1.Noll Physiological Research CenterPennsylvania State UniversityUniversity ParkUSA

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