The biochemistry of aging muscle

Between the ages of 20 and 80, humans lose approximately 20-30% of their skeletal muscle mass. This age-related loss of muscle mass, sometimes described as 'sarcopenia of old age', is the consequence of complicated multifactorial processes and is commonly associated with osteopenia or osteoporosis. Consequences of the aging changes in muscle are declining physiological function and loss of muscle strength, typically associated with reduced physical activities. Consequently, falls and subsequent serious injuries are prevalent in the elderly. Thus, it is imperative to try and understand the processes, leading to age-related muscle loss, in order to develop means to retard this phenomenon leading to improved quality of life in the elderly. It is possible to divide the causes of muscle aging to intrinsic factors, involving changes at the molecular and cellular levels, and to extrinsic or environmental factors. The purpose of this review is to describe some of the biochemical processes and the possible mechanisms of muscle aging and to evaluate the importance of various extrinsic factors such as nutrition, exercise and limb immobilization. Changes in the aging skeletal muscle are reviewed with regard to: (a) enzyme activities, protein turnover and repair capacities (b) mitochondrial functioning and energy reserve systems (c) ion content and regulation (d) oxidative stress and free radicals (e) nutrition and caloric restriction (f) exercise and limb immobilization.

[1]  M. Vitiello,et al.  Somatomedin-C levels in healthy young and old men: relationship to peak and 24-hour integrated levels of growth hormone. , 1985, Journal of gerontology.

[2]  K. Nair,et al.  Age effect on transcript levels and synthesis rate of muscle MHC and response to resistance exercise. , 2001, American journal of physiology. Endocrinology and metabolism.

[3]  S. Pierno,et al.  Aging and chloride channel regulation in rat fast-twitch muscle fibres , 1994, Pflügers Archiv.

[4]  N. J. Crisona,et al.  Muscle satellite cells from dystrophic (mdx) mice have elevated levels of heparan sulphate proteoglycan receptors for fibroblast growth factor , 2004, Journal of Muscle Research & Cell Motility.

[5]  C. Sen,et al.  Oxidative Stress in Skeletal Muscle , 1998, MCBU Molecular and Cell Biology Updates.

[6]  A. Munnich,et al.  Biochemical parameters for the diagnosis of mitochondrial respiratory chain deficiency in humans, and their lack of age-related changes. , 1998, The Biochemical journal.

[7]  C. Sen.  Oxidants and antioxidants in exercise. , 1995, Journal of applied physiology.

[8]  E. Carmeli,et al.  Capacity for Recovery and Possible Mechanisms in Immobilization Atrophy of Young and Old Animals , 2001, Annals of the New York Academy of Sciences.

[9]  C. Sen,et al.  Skeletal muscle and heart antioxidant defences in response to sprint training. , 1996, Acta physiologica Scandinavica.

[10]  C. Schöneich,et al.  In vivo aging of rat skeletal muscle sarcoplasmic reticulum Ca-ATPase. Chemical analysis and quantitative simulation by exposure to low levels of peroxyl radicals. , 1997, Biochimica et biophysica acta.

[11]  E. Stadtman,et al.  Protein Oxidation in Aging, Disease, and Oxidative Stress* , 1997, The Journal of Biological Chemistry.

[12]  S. Powers,et al.  Exercise training-induced alterations in skeletal muscle antioxidant capacity: a brief review. , 1999, Medicine and science in sports and exercise.

[13]  C. Cross,et al.  Modification of plasma proteins by cigarette smoke as measured by protein carbonyl formation. , 1992, The Biochemical journal.

[14]  D. Allison,et al.  Caloric restriction of rhesus monkeys lowers oxidative damage in skeletal muscle , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[15]  R. Weindruch,et al.  Caloric restriction reduces fiber loss and mitochondrial abnormalities in aged rat muscle , 1997, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[16]  B. Yu,et al.  Effect of chronic food restriction in aging rats II. Liver cytosolic antioxidants and related enzymes , 1989, Mechanisms of Ageing and Development.

[17]  B. Sobel,et al.  Aging and high concentrations of glucose potentiate injury to mitochondrial DNA. , 1999, Free radical biology & medicine.

[18]  M. Messi,et al.  L-Type Ca(2+) channel charge movement and intracellular Ca(2+) in skeletal muscle fibers from aging mice. , 2000, Biophysical journal.

[19]  S. Welle,et al.  Myofibrillar protein synthesis in young and old human subjects after three months of resistance training. , 1995, The American journal of physiology.

[20]  Ana Navarro-Arévalo,et al.  Myocardial and skeletal muscle aging and changes in oxidative stress in relationship to rigorous exercise training , 1999, Mechanisms of Ageing and Development.

[21]  R. S. Sohal,et al.  Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse , 1994, Mechanisms of Ageing and Development.

[22]  F. Booth,et al.  Myogenic regulatory factors during regeneration of skeletal muscle in young, adult, and old rats. , 1997, Journal of applied physiology.

[23]  K. Nair,et al.  Effects of Aging on Mitochondrial DNA Copy Number and Cytochromec Oxidase Gene Expression in Rat Skeletal Muscle, Liver, and Heart* , 2000, The Journal of Biological Chemistry.

[24]  A. Linnane,et al.  The Universality of Bioenergetic Disease: Age‐associated Cellular Bioenergetic Degradation and Amelioration Therapy , 1998, Annals of the New York Academy of Sciences.

[25]  C M McCay,et al.  The effect of retarded growth upon the length of life span and upon the ultimate body size. 1935. , 1935, Nutrition.

[26]  A. Reznick,et al.  Effect of growth hormone on oxidative stress in immobilized muscles of old animals , 1998 .

[27]  D. Cai,et al.  Age‐related changes of aqueous protein profiles in rat fast and slow twitch skeletal muscles , 2000, Electrophoresis.

[28]  K. Nair.  Age-related changes in muscle. , 2000, Mayo Clinic proceedings.

[29]  D. Hostler,et al.  Fiber Type Composition of the Vastus Lateralis Muscle of Young Men and Women , 2000 .

[30]  O. Delbono,et al.  Effectiveness of caloric restriction in preventing age-related changes in rat skeletal muscle. , 1998, Biochemical and biophysical research communications.

[31]  S. Morimoto,et al.  Role of troponin I isoform switching in determining the pH sensitivity of Ca(2+) regulation in developing rabbit cardiac muscle. , 2000, Biochemical and biophysical research communications.

[32]  M. Ermini.  Ageing changes in mammalian skeletal muscle: biochemical studies. , 1976, Gerontology.

[33]  A. Aiyar,et al.  Effect of diet restriction on some biochemical parameters related to aging in mice. , 1983, The Journal of nutrition.

[34]  D. Jones,et al.  Effects of aging on sarcoplasmic reticulum function and contraction duration in skeletal muscles of the rat. , 1996, The American journal of physiology.

[35]  P. Esselman,et al.  Oxidative capacity and ageing in human muscle , 2000, The Journal of physiology.

[36]  F. Bardag-Gorce,et al.  Changes in 20S proteasome activity during ageing of the LOU rat , 1999, Molecular Biology Reports.

[37]  D. Camerino,et al.  ATP-sensitive K+ channels of skeletal muscle fibers from young adult and aged rats: possible involvement of thiol-dependent redox mechanisms in the age-related modifications of their biophysical and pharmacological properties. , 1994, Molecular pharmacology.

[38]  H. Kobayashi,et al.  Age change of skeletal muscles of rats. , 1971, Gerontologia.

[39]  B. Carlson.  Factors influencing the repair and adaptation of muscles in aged individuals: satellite cells and innervation. , 1995, The journals of gerontology. Series A, Biological sciences and medical sciences.

[40]  H. C. Lee,et al.  Simultaneous Increase of Mitochondrial DNA Deletions and Lipid Peroxidation in Human Aging a , 1996, Annals of the New York Academy of Sciences.

[41]  J. Holloszy,et al.  Longevity of exercising male rats: effect of an antioxidant supplemented diet , 1998, Mechanisms of Ageing and Development.

[42]  Y. Itokawa,et al.  Mechanism of oxidative stress in skeletal muscle atrophied by immobilization. , 1993, The American journal of physiology.

[43]  C. Schöneich,et al.  Protein modification during biological aging: selective tyrosine nitration of the SERCA2a isoform of the sarcoplasmic reticulum Ca2+-ATPase in skeletal muscle. , 1999, The Biochemical journal.

[44]  J. Holloszy,et al.  Markers of protein oxidation by hydroxyl radical and reactive nitrogen species in tissues of aging rats. , 1998, American journal of physiology. Regulatory, integrative and comparative physiology.

[45]  R. S. Sohal,et al.  Age-related changes in activities of mitochondrial electron transport complexes in various tissues of the mouse. , 2000, Archives of biochemistry and biophysics.

[46]  L. Packer,et al.  Exercise, oxidative damage and effects of antioxidant manipulation. , 1992, The Journal of nutrition.

[47]  D. Harman,et al.  The aging process. , 1981, Basic life sciences.

[48]  W. Millard,et al.  Altered IGF-I and IGFBPs in senescent male and female rats. , 1999, The journals of gerontology. Series A, Biological sciences and medical sciences.

[49]  T. Kaneko,et al.  The effect of exercise training on oxidative damage of lipids, proteins, and DNA in rat skeletal muscle: evidence for beneficial outcomes. , 1999, Free radical biology & medicine.

[50]  R. Weindruch,et al.  Influences of dietary restriction and age on liver enzyme activities and lipid peroxidation in mice. , 1987, The Journal of nutrition.

[51]  Peter Johnson,et al.  Cadiac and skeletal muscle enzymes levels in hypertensive and ageing rats , 1993 .

[52]  O. Pansarasa,et al.  Age-dependent changes of antioxidant activities and markers of free radical damage in human skeletal muscle. , 1999, Free radical biology & medicine.

[53]  Michael G. Bemben,et al.  Age-Related Alterations in Muscular Endurance , 1998, Sports medicine.

[54]  M. Kanter.  Free radicals, exercise and antioxidant supplementation. , 1994, The Proceedings of the Nutrition Society.

[55]  P. Saari,et al.  Age- and sex-related differences in lipid peroxidation of mouse cardiac and skeletal muscles. , 1988, Comparative biochemistry and physiology. B, Comparative biochemistry.

[56]  J. Fridén,et al.  Eccentric exercise-induced injuries to contractile and cytoskeletal muscle fibre components. , 2001, Acta physiologica Scandinavica.

[57]  R. Coleman,et al.  Muscle recovery after immobilisation by external fixation. , 1999, The Journal of bone and joint surgery. British volume.

[58]  Ronenn Roubenoff,et al.  From the Chicago MeetingsSarcopenia , 2001 .

[59]  R. Eccles,et al.  Depolarization of afferent terminals evoked by muscle stretch. , 1965, The Journal of physiology.

[60]  D. Edington,et al.  Exercise and longevity: evidence for a threshold age. , 1972, Journal of gerontology.

[61]  S. Papa,et al.  Decline with age of the respiratory chain activity in human skeletal muscle. , 1994, Biochimica et biophysica acta.

[62]  P. Nagley,et al.  Differential occurrence of mutations in mitochondrial DNA of human skeletal muscle during aging , 1998, Human mutation.

[63]  R. Burcelin,et al.  Regulation of Hexokinase II Gene Expression by Glucose Flux in Skeletal Muscle* , 1996, The Journal of Biological Chemistry.

[64]  D. Taillandier,et al.  Sensitivity and protein turnover response to glucocorticoids are different in skeletal muscle from adult and old rats. Lack of regulation of the ubiquitin-proteasome proteolytic pathway in aging. , 1995, The Journal of clinical investigation.

[65]  L. Packer,et al.  Oxidative damage to proteins: spectrophotometric method for carbonyl assay. , 1994, Methods in enzymology.

[66]  Eli Carmeli,et al.  Muscle Strength and Mass of Lower Extremities in Relation to Functional Abilities in Elderly Adults , 2000, Gerontology.

[67]  L. Ji,et al.  Aging and acute exercise enhance free radical generation in rat skeletal muscle. , 1999, Journal of applied physiology.

[68]  M. Hamilton,et al.  Association of insulin-like growth factor mRNA expressions with muscle regeneration in young, adult, and old rats. , 1997, The American journal of physiology.

[69]  R. Fielding,et al.  Exercise, free radical generation, and aging , 1997, Aging.

[70]  T. B. Symons,et al.  Functional and metabolic consequences of sarcopenia. , 2001, Canadian journal of applied physiology = Revue canadienne de physiologie appliquee.

[71]  M. Reid.  Nitric oxide, reactive oxygen species, and skeletal muscle contraction. , 2001, Medicine and science in sports and exercise.

[72]  J. Aiken,et al.  Mitochondrial DNA deletion mutations colocalize with segmental electron transport system abnormalities, muscle fiber atrophy, fiber splitting, and oxidative damage in sarcopenia , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[73]  D. Bigelow,et al.  The nucleotide-binding site of the sarcoplasmic reticulum Ca-ATPase is conformationally altered in aged skeletal muscle. , 1999, Biochemistry.

[74]  E. Carmeli,et al.  Effect of growth hormone on gastrocnemius muscle of aged rats after immobilization: biochemistry and morphology. , 1993, Journal of applied physiology.

[75]  C. K. Lee,et al.  Gene expression profile of aging and its retardation by caloric restriction. , 1999, Science.

[76]  R. Weindruch,et al.  Oxidative Stress, Caloric Restriction, and Aging , 1996, Science.

[77]  C. Elger,et al.  Flux control of cytochrome c oxidase in human skeletal muscle. , 2000, The Journal of biological chemistry.

[78]  K. Nair,et al.  Mechanisms of sarcopenia of aging. , 1999, Journal of endocrinological investigation.

[79]  B. Yu,et al.  Aging and oxidative stress: modulation by dietary restriction. , 1996, Free radical biology & medicine.

[80]  R. Armstrong,et al.  Mechanisms of Exercise-Induced Muscle Fibre Injury , 1991, Sports medicine.

[81]  J. Lawler,et al.  Relationship between NADP-specific isocitrate dehydrogenase and glutathione peroxidase in aging rat skeletal muscle , 2001, Mechanisms of Ageing and Development.

[82]  E. Carmeli,et al.  The Physiology and Biochemistry of Skeletal Muscle Atrophy as a Function of Age , 1994, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[83]  L. Packer,et al.  The threshold of age in exercise and antioxidants action. , 1992, EXS.

[84]  Ageing: Effects on oxidative function of skeletal muscle in vivo , 1997 .

[85]  A. Reznick,et al.  Characterization of alkaline and acid phosphatases from skeletal muscles of young and old rats. , 1997, Archives of gerontology and geriatrics.

[86]  V. Baracos,et al.  Restoration of insulin-like growth factor I action in skeletal muscle of old mice. , 1998, American journal of physiology. Endocrinology and metabolism.

[87]  A. Linnane,et al.  The age‐associated decrease in the amount of amplifiable full‐length mitochondrial DNA in human skeletal muscle , 1998, Biochemistry and molecular biology international.

[88]  Michelle M. Porter.  The effects of strength training on sarcopenia. , 2001, Canadian journal of applied physiology = Revue canadienne de physiologie appliquee.

[89]  K. Yasuda,et al.  Carbonylated proteins in aging and exercise: immunoblot approaches , 1999, Mechanisms of Ageing and Development.

[90]  B. Wiederanders,et al.  Accumulation of inactive cathepsin D in old rats , 1984, Mechanisms of Ageing and Development.

[91]  M. Jackson,et al.  Exercise, oxidative stress and ageing , 2000, Journal of anatomy.

[92]  D. Cocchi,et al.  Effects of chronic growth hormone treatment in aged rats on the biophysical and pharmacological properties of skeletal muscle chloride channels , 1997, British journal of pharmacology.

[93]  H. Kaminski,et al.  Nitric oxide synthase in aging rat skeletal muscle , 1999, Mechanisms of Ageing and Development.

[94]  R. Kawamori,et al.  Impairment of insulin-induced vasodilation is associated with muscle insulin resistance in type 2 diabetes. , 2000, Diabetes research and clinical practice.

[95]  B. Yu,et al.  Effect of chronic food restriction in aging rats I. Liver subcellular membranes , 1989, Mechanisms of Ageing and Development.

[96]  A Margreth,et al.  Sarcoplasmic reticulum in aged skeletal muscle. , 1999, Acta physiologica Scandinavica.

[97]  Y. Hellsten,et al.  Effect of sprint cycle training on activities of antioxidant enzymes in human skeletal muscle. , 1996, Journal of applied physiology.

[98]  L. Packer,et al.  Vitamin E inhibits protein oxidation in skeletal muscle of resting and exercised rats. , 1992, Biochemical and biophysical research communications.

[99]  K. Yarasheski,et al.  Muscle-specific mutations accumulate with aging in critical human mtDNA control sites for replication , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[100]  M. Dossena,et al.  The effects of aging on enzyme activities and metabolite concentrations in skeletal muscle from sedentary male and female subjects , 2000, Experimental Gerontology.

[101]  R. Holliday.  Somatic mutations and ageing. , 2000, Mutation research.

[102]  H. Alessio,et al.  Exercise-induced oxidative stress before and after vitamin C supplementation. , 1997, International journal of sport nutrition.

[103]  S. Melov,et al.  Marked increase in the number and variety of mitochondrial DNA rearrangements in aging human skeletal muscle , 1995 .

[104]  G. Cartee,et al.  Effect of long-term caloric restriction on GLUT4, phosphatidylinositol-3 kinase p85 subunit, and insulin receptor substrate-1 protein levels in rhesus monkey skeletal muscle. , 2000, The journals of gerontology. Series A, Biological sciences and medical sciences.

[105]  B. Yu,et al.  Can antioxidant supplementation slow the aging process? , 1998, BioFactors.

[106]  J. Ward,et al.  Should Antioxidant Vitamins be Routinely Recommended for Older People? , 1998, Drugs & aging.

[107]  IGF-I restores satellite cell proliferative potential in immobilized old skeletal muscle , 2000 .

[108]  B. Hansen,et al.  Calorie restriction in nonhuman primates: mechanisms of reduced morbidity and mortality. , 1999, Toxicological sciences : an official journal of the Society of Toxicology.

[109]  L. Martineau,et al.  Age-associated alterations in cardiac and skeletal muscle glucose transporters, insulin and IGF-1 receptors, and PI3-kinase protein contents in the C57BL/6 mouse , 1999, Mechanisms of Ageing and Development.

[110]  D. Ferrington,et al.  Altered Turnover of Calcium Regulatory Proteins of the Sarcoplasmic Reticulum in Aged Skeletal Muscle* , 1998, The Journal of Biological Chemistry.

[111]  Nair Ks.  Muscle Protein Turnover: Methodological Issues and the Effect of Aging , 1995 .

[112]  H. Degens,et al.  Glyceraldehyde-3-phosphate dehydrogenase varies with age in glycolytic muscles of rats. , 2000, The journals of gerontology. Series A, Biological sciences and medical sciences.

[113]  E. Carmeli,et al.  Recovery of muscles of old rats after hindlimb immobilisation by external fixation is impaired compared with those of young rats , 2001, Experimental Gerontology.

[114]  A. Giuliani,et al.  Exercise, free radical generation and vitamins , 1997, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[115]  G. Radda,et al.  Total ion content of skeletal and cardiac muscle in the mdx mouse dystrophy: Ca2+ is elevated at all ages , 1991, Journal of the Neurological Sciences.