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Sports Medicine

01.06.2005 | Review Article

The Role of Apoptosis in Age-Related Skeletal Muscle Atrophy

verfasst von: Amie J. Dirks, Dr Christiaan Leeuwenburgh

Erschienen in: Sports Medicine | Ausgabe 6/2005

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Abstract

Skeletal myocyte atrophy and death contribute to sarcopenia, a condition associated with normal aging. By 80 years of age, it is estimated that humans generally lose 30–40% of skeletal muscle fibres. The mechanism for this loss is unknown; however, it may involve apoptosis. Mitochondrial dysfunction and sarcoplasmic reticulum (SR) stress that occurs with age may be possible stimuli inducing apoptosis. Hence, mitochondria and SR may be important organelles within skeletal myocytes responsible for apoptosis signalling. The activation of apoptosis may be partly responsible for the initiation of muscle protein degradation, loss of muscle nuclei associated with local atrophy, and cell death of the myocyte. Exercise training and caloric restriction are two interventions known to enhance skeletal muscle function. The effects of these interventions on apoptosis are discussed.
Literatur
1.
Leeuwenburgh C. Role of apoptosis in sarcopenia. J Gerontol A Biol Sci Med Sci 2003; 58: 999–1001PubMedCrossRef
2.
Dirks AJ, Leeuwenburgh C. Aging and lifelong calorie restriction result in adaptations of skeletal muscle apoptosis repressor, apoptosis-inducing factor, X-linked inhibitor of apoptosis, caspase-3, and caspase-12. Free Radic Biol Med 2004; 36: 27–39PubMedCrossRef
3.
Drew B, Phaneuf S, Dirks A, et al. Effects of aging and caloric restriction on mitochondrial energy production in gastrocnemius muscle and heart. Am J Physiol Regul Integr Comp Physiol 2003; 284: R474–80
4.
Dirks A, Leeuwenburgh C. Apoptosis in skeletal muscle with aging. Am J Physiol Regul Integr Comp Physiol 2002; 282: R519–27
5.
Bua EA, McKiernan SH, Wanagat J, et al. Mitochondrial abnormalities are more frequent in muscles undergoing sarcopenia. J Appl Physiol 2002; 92: 2617–24PubMed
6.
Roubenoff R. Sarcopenia and its implications for the elderly. Eur J Clin Nutr 2000; 54: S40–7CrossRef
7.
Marcell TJ. Sarcopenia: causes, consequences, and preventions. J Gerontol A Biol Sci Med Sci 2003; 58 (10): M911–6CrossRef
8.
Vellas B, Gillette-Guyonnet S, Nourhashemi F, et al. Falls, frailty and osteoporosis in the elderly: a public health problem. Rev Med Interne 2000; 21: 608–13PubMedCrossRef
9.
Moulias R, Meaume S, Raynaud-Simon A. Sarcopenia, hypermetabolism, and aging. Z Gerontol Geriatr 1999; 32: 425–32PubMedCrossRef
10.
Rantanen T, Guralnik JM, Foley D, et al. Midlife hand grip strength as a predictor of old age disability. JAMA 1999; 281: 558–60PubMedCrossRef
11.
Metter EJ, Talbot LA, Schrager M, et al. Skeletal muscle strength as a predictor of all-cause mortality in healthy men. J Gerontol A Biol Sci Med Sci 2002; 57: B359–65CrossRef
12.
Janssen HC, Samson MM, Meeuwsen IB, et al. Strength, mobility and falling in women referred to a geriatric outpatient clinic. Aging Clin Exp Res 2004; 16: 122–5PubMed
13.
Janssen I, Baumgartner RN, Ross R, et al. Skeletal muscle cutpoints associated with elevated physical disability risk in older men and women. Am J Epidemiol 2004; 159: 413–21PubMedCrossRef
14.
Lexell J. Human aging, muscle mass, and fiber type composition. J Gerontol A Biol Sci Med Sci 1995; 50: 11–6PubMed
15.
Leeuwenburgh C, Wagner P, Holloszy JO, et al. Caloric restriction attenuates dityrosine cross-linking of cardiac and skeletal muscle proteins in aging mice. Arch Biochem Biophys 1997; 346: 74–80PubMedCrossRef
16.
Faulkner JA, Brooks SV, Zerba E. Muscle atrophy and weakness with aging: contraction-induced injury as an underlying mechanism. J Gerontol A Biol Sci Med Sci 1995; 50: 124–9PubMed
17.
Wallace DC. Mitochondrial genetics: a paradigm for aging and degenerative diseases? Science 1992; 256: 628–32PubMedCrossRef
18.
Bejma J, Ji LL. Aging and acute exercise enhance free radical generation in rat skeletal muscle. J Appl Physiol 1999; 87: 465–70PubMed
19.
Lee CM, Aspnes LE, Chung SS, et al. Influences of caloric restriction on age-associated skeletal muscle fiber characteristics and mitochondrial changes in rats and mice. Ann N Y Acad Sci 1998; 854: 182–91PubMedCrossRef
20.
Aspnes LE, Lee CM, Weindruch R, et al. Caloric restriction reduces fiber loss and mitochondrial abnormalities in aged rat muscle. FASEB J 1997; 11: 573–81PubMed
21.
Wanagat J, Cao Z, Pathare P, et al. Mitochondrial DNA deletion mutations colocalize with segmental electron transport system abnormalities, muscle fiber atrophy, fiber splitting, and oxidative damage in sarcopenia. FASEB J 2001; 15: 322–32PubMedCrossRef
22.
Allen DL, Linderman JK, Roy RR, et al. Apoptosis: a mechanism contributing to remodeling of skeletal muscle in response to hindlimb unweighting. Am J Physiol 1997; 273: C579–87
23.
Bhasin S. Testosterone supplementation for aging-associated sarcopenia. J Gerontol A Biol Sci Med Sci 2003; 58: 1002–8PubMedCrossRef
24.
25.
Alway SE, Degens H, Krishnamurthy G, et al. Denervation stimulates apoptosis but not Id2 expression in hindlimb muscles of aged rats. J Gerontol A Biol Sci Med Sci 2003; 58: 687–97PubMedCrossRef
26.
Wallace DC. Mitochondrial genetics: a paradigm for aging and degenerative diseases? Science 1992; 256: 628–32PubMedCrossRef
27.
Sohal RS, Weindruch R. Oxidative stress, caloric restriction, and aging. Science 1996; 273: 59–63PubMedCrossRef
28.
Gredilla R, Sanz A, Lopez-Torres M, et al. Caloric restriction decreases mitochondrial free radical generation at complex I and lowers oxidative damage to mitochondrial DNA in the rat heart. FASEB J 2001; 15: 1589–91PubMed
29.
30.
Cadenas E, Davies KJ. Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 2000; 29: 222–30PubMedCrossRef
31.
de Grey AD. The reductive hotspot hypothesis: an update. Arch Biochem Biophys 2000; 373: 295–301PubMedCrossRef
32.
Zainal TA, Oberley TD, Allison DB, et al. Caloric restriction of rhesus monkeys lowers oxidative damage in skeletal muscle. FASEB J 2000; 14: 1825–36PubMedCrossRef
33.
Lopez-Torres M, Gredilla R, Sanz A, et al. Influence of aging and long-term caloric restriction on oxygen radical generation and oxidative DNA damage in rat liver mitochondria. Free Radic Biol Med 2002; 32: 882–9PubMedCrossRef
34.
Taylor RW, Taylor GA, Durham SE, et al. The determination of complete human mitochondrial DNA sequences in single cells: implications for the study of somatic mitochondrial DNA point mutations. Nucleic Acids Res 2001; 29: E74CrossRef
35.
Ramakrishna R, Edwards JS, McCulloch A, et al. Flux-balance analysis of mitochondrial energy metabolism: consequences of systemic stoichiometric constraints. Am J Physiol Regul Integr Comp Physiol 2001; 280: R695–704
36.
37.
Pollack M, Leeuwenburgh C. Apoptosis and aging: role of the mitochondria. J Gerontol A Biol Sci Med Sci 2001; 56: B475–82CrossRef
38.
Phaneuf S, Leeuwenburgh C. Cytochrome c release from mitochondria in the aging heart: a possible mechanism for apoptosis with age. Am J Physiol Regul Integr Comp Physiol 2002; 282: R423–30
39.
Sastre J, Pallardo FV, Vina J. Mitochondrial oxidative stress plays a key role in aging and apoptosis. IUBMB Life 2000; 49: 427–35PubMedCrossRef
40.
Mazat JP, Letellier T, Bedes F, et al. Metabolic control analysis and threshold effect in oxidative phosphorylation: implications for mitochondrial pathologies. Mol Cell Biochem 1997; 174: 143–8PubMedCrossRef
41.
Conley KE, Jubrias SA, Esselman PC. Oxidative capacity and ageing in human muscle. J Physiol 2000; 526 (Pt 1): 203–10PubMedCrossRef
42.
Alway SE, Degens H, Lowe DA, et al. Increased myogenic repressor Id mRNA and protein levels in hindlimb muscles of aged rats. Am J Physiol Regul Integr Comp Physiol 2002; 282: R411–22
43.
Baynes JW. The Maillard hypothesis on aging: time to focus on DNA. Ann N Y Acad Sci 2002; 959: 360–7PubMedCrossRef
44.
Cefalu WT, Bell-Farrow AD, Wang ZQ, et al. Caloric restriction decreases age-dependent accumulation of the glycoxidation products, N epsilon-(carboxymethyl)lysine and pentosidine, in rat skin collagen. J Gerontol A Biol Sci Med Sci 1995; 50: B337–41
45.
Ramamurthy B, Jones AD, Larsson L. Glutathione reverses early effects of glycation on myosin function. Am J Physiol Cell Physiol 2003; 285 (2): C419–24
46.
Alway SE, Degens H, Krishnamurthy G, et al. Potential role for Id myogenic repressors in apoptosis and attenuation of hypertrophy in muscles of aged rats. Am J Physiol Cell Physiol 2002; 283: C66–76
47.
McArdle A, Maglara A, Appleton P, et al. Apoptosis in multinucleated skeletal muscle myotubes. Lab Invest 1999; 79: 1069–76PubMed
48.
Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972; 26: 239–57PubMedCrossRef
49.
Kluck RM, Bossy-Wetzel E, Green DR, et al. The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 1997; 275: 1132–6PubMedCrossRef
50.
51.
Kajstura J, Cheng W, Sarangarajan R, et al. Necrotic and apoptotic myocyte cell death in the aging heart of Fischer 344 rats. Am J Physiol 1996; 271: H1215–28
52.
Nitahara JA, Cheng W, Liu Y, et al. Intracellular calcium, DNase activity and myocyte apoptosis in aging Fischer 344 rats. J Mol Cell Cardiol 1998; 30: 519–35PubMedCrossRef
53.
Maglara A, Jackson MJ, McArdle A. Programmed cell death in skeletal muscle [letter]. Biochem Soc Trans 1998; 26: S259
54.
Strasser H, Tiefenthaler M, Steinlechner M, et al. Age dependent apoptosis and loss of rhabdosphincter cells. J Urol 2000; 164: 1781–5PubMedCrossRef
55.
Strasser H, Tiefenthaler M, Steinlechner M, et al. Urinary incontinence in the elderly and age-dependent apoptosis of rhabdosphincter cells. Lancet 1999; 354: 918–9PubMedCrossRef
56.
Warner HR. Recent progress in understanding the relationships among aging, replicative senescence, cell turnover and cancer. In Vivo 2002; 16: 393–6PubMed
57.
Denis U, Lecomte M, Paget C, et al. Advanced glycation end-products induce apoptosis of bovine retinal pericytes in culture: involvement of diacylglycerol/ceramide production and oxidative stress induction. Free Radic Biol Med 2002; 33: 236–47PubMedCrossRef
58.
Cellek S, Qu W, Schmidt AM, et al. Synergistic action of advanced glycation end products and endogenous nitric oxide leads to neuronal apoptosis in vitro: a new insight into selective nitrergic neuropathy in diabetes. Diabetologia 2004; 47: 331–9PubMedCrossRef
59.
Borisov AB, Carlson BM. Cell death in denervated skeletal muscle is distinct from classical apoptosis. Anat Rec 2000; 258: 305–18PubMedCrossRef
60.
Cortopassi GA, Wong A. Mitochondria in organismal aging and degeneration. Biochim Biophys Acta 1999; 1410 (2): 183–93PubMedCrossRef
61.
Green D, Kroemer G. The central executioners of apoptosis: caspases or mitochondria? Trends Cell Biol 1998; 8: 267–71PubMedCrossRef
62.
Pollack M, Phaneuf S, Dirks A, et al. The role of apoptosis in the normal aging brain, skeletal muscle, and heart. Ann N Y Acad Sci 2002; 959: 93–107PubMedCrossRef
63.
Renatus M, Stennicke HR, Scott FL, et al. Dimer formation drives the activation of the cell death protease caspase 9. Proc Natl Acad Sci U S A 2001; 98: 14250–5PubMedCrossRef
64.
Sun XM, MacFarlane M, Zhuang J, et al. Distinct caspase cascades are initiated in receptor-mediated and chemical-induced apoptosis. J Biol Chem 1999; 274: 5053–60PubMedCrossRef
65.
Zimmermann KC, Bonzon C, Green DR. The machinery of programmed cell death. Pharmacol Ther 2001; 92: 57–70PubMedCrossRef
66.
Kroemer G. B709 mitochondrial control of cell death [letter]. Sci World J 2001; 1: 48CrossRef
67.
Bossy-Wetzel E, Green DR. Caspases induce cytochrome c release from mitochondria by activating cytosolic factors. J Biol Chem 1999; 274: 17484–90PubMedCrossRef
68.
Ekhterae D, Lin Z, Lundberg MS, et al. ARC inhibits cytochrome c release from mitochondria and protects against hypoxia-induced apoptosis in heart-derived H9c2 cells. Circ Res 1999; 85: e70–7CrossRef
69.
Liston P, Young SS, Mackenzie AE, et al. Life and death decisions: the role of the IAPs in modulating programmed cell death. Apoptosis 1997; 2: 423–41PubMedCrossRef
70.
Daugas E, Nochy D, Ravagnan L, et al. Apoptosis-inducing factor (AIF): a ubiquitous mitochondrial oxidoreductase involved in apoptosis. FEBS Lett 2000; 476: 118–23PubMedCrossRef
71.
Daugas E, Susin SA, Zamzami N, et al. Mitochondrio-nuclear translocation of AIF in apoptosis and necrosis. FASEB J 2000; 14: 729–39PubMed
72.
Larner SF, Hayes RL, McKinsey DM, et al. Increased expression and processing of caspase-12 after traumatic brain injury in rats. J Neurochem 2004; 88: 78–90PubMedCrossRef
73.
Rao RV, Hermel E, Castro-Obregon S, et al. Coupling endoplasmic reticulum stress to the cell death program: mechanism of caspase activation. J Biol Chem 2001; 276: 33869–74PubMedCrossRef
74.
Shibata M, Hattori H, Sasaki T, et al. Activation of caspase-12 by endoplasmic reticulum stress induced by transient middle cerebral artery occlusion in mice. Neuroscience 2003; 118: 491–9PubMedCrossRef
75.
Squier TC, Bigelow DJ. Protein oxidation and age-dependent alterations in calcium homeostasis. Front Biosci 2000; 5: D504–26CrossRef
76.
McKiernan S, Bua E, McGorray J, et al. Early-onset calorie restriction conserves fiber number in aging rat skeletal muscle. FASEB J 2004; 18 (3): 580–1PubMed
77.
Bua EA, McKiernan SH, Aiken JM. Calorie restriction limits the generation but not the progression of mitochondrial abnormalities in aging skeletal muscle. FASEB J 2004; 18 (3): 582–4PubMed
78.
Nakagawa T, Yuan J. Cross-talk between two cysteine protease families: activation of caspase-12 by calpain in apoptosis. J Cell Biol 2000; 150: 887–94PubMedCrossRef
79.
Nakagawa T, Zhu H, Morishima N, et al. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 2000; 403: 98–103PubMedCrossRef
80.
Adams V, Gielen S, Hambrecht R, et al. Apoptosis in skeletal muscle. Front Biosci 2001; 6: D1-D11CrossRef
81.
Allen DL, Roy RR, Edgerton VR. Myonuclear domains in muscle adaptation and disease. Muscle Nerve 1999; 22: 1350–60PubMedCrossRef
82.
McCartney N, Hicks AL, Martin J, et al. A longitudinal trial of weight training in the elderly: continued improvements in year 2. J Gerontol A Biol Sci Med Sci 1996; 51: B425–33CrossRef
83.
Nelson ME, Fiatarone MA, Morganti CM, et al. Effects of high-intensity strength training on multiple risk factors for osteoporotic fractures: a randomized controlled trial. JAMA 1994; 272: 1909–14PubMedCrossRef
84.
Bales CW, Ritchie CS. Sarcopenia, weight loss, and nutritional frailty in the elderly. Annu Rev Nutr 2002; 22: 309–23PubMedCrossRef
85.
Vincent KR, Vincent HK, Braith RW, et al. Resistance exercise training attenuates exercise-induced lipid peroxidation in the elderly. Eur J Appl Physiol 2002; 87: 416–23PubMedCrossRef
86.
Siu PM, Bryner RW, Martyn JK, et al. Apoptotic adaptations from exercise training in skeletal and cardiac muscles. FASEB J 2004; 18 (10): 1150–2PubMed
87.
Kobayashi Y, Kume A, Li M, et al. Chaperones Hsp70 and Hsp40 suppress aggregate formation and apoptosis in cultured neuronal cells expressing truncated androgen receptor protein with expanded polyglutamine tract. J Biol Chem 2000; 275: 8772–8PubMedCrossRef
88.
Cande C, Cohen I, Daugas E, et al. Apoptosis-inducing factor (AIF): a novel caspase-independent death effector released from mitochondria. Biochimie 2002; 84: 215–22PubMedCrossRef
89.
Weindruch R, Walford RL, Fligiel S, et al. The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake. J Nutr 1986; 116: 641–54PubMed
90.
Sohal RS, Ku HH, Agarwal S, et al. Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse. Mech Ageing Dev 1994; 74: 121–33PubMedCrossRef
91.
Lee CK, Prolla TA, Weindruch R. Caloric intake, oxidative stress and aging. Sci World J 2001; 1: 85CrossRef
92.
Payne AM, Dodd SL, Leeuwenburgh C. Life-long calorie restriction in Fischer 344 rats attenuates age-related loss in skeletal muscle-specific force and reduces extracellular space. J Appl Physiol 2003; 95: 2554–62PubMed
Metadaten
Titel
The Role of Apoptosis in Age-Related Skeletal Muscle Atrophy
verfasst von
Amie J. Dirks
Dr Christiaan Leeuwenburgh
Publikationsdatum
01.06.2005
Verlag
Springer International Publishing
Erschienen in
Sports Medicine / Ausgabe 6/2005
Print ISSN: 0112-1642
Elektronische ISSN: 1179-2035
DOI
https://doi.org/10.2165/00007256-200535060-00002

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