Apoptosis in Skeletal Myocytes: A Potential Target for Interventions against Sarcopenia and Physical Frailty – A Mini-Review

Background: Sarcopenia, the age-related loss of muscle mass and function, represents a relevant public health issue due to its high prevalence and detrimental consequences. While the exact mechanisms underlying the pathogenesis of sarcopenia are not clear, growing experimental evidence indicates tha...

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Veröffentlicht in:Gerontology (Basel) Jg. 58; H. 2; S. 99 - 106
Hauptverfasser: Marzetti, Emanuele, Calvani, Riccardo, Bernabei, Roberto, Leeuwenburgh, Christiaan
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Basel, Switzerland Karger 01.02.2012
S. Karger AG
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ISSN:0304-324X, 1423-0003, 1423-0003
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Abstract Background: Sarcopenia, the age-related loss of muscle mass and function, represents a relevant public health issue due to its high prevalence and detrimental consequences. While the exact mechanisms underlying the pathogenesis of sarcopenia are not clear, growing experimental evidence indicates that progressive myonuclear elimination over the course of aging via an apoptosis-like process may represent a converging mechanism through which muscle atrophy and loss of physical function develop. Notably, the proapoptotic environment taking place in aged muscle appears amenable to interventions. Objective: We aimed at providing (1) an overview of signaling pathways of apoptosis relevant to sarcopenia, and (2) a review of the literature supporting myocyte apoptosis as a target for interventions against muscle aging. Methods: We summarized findings from studies focused on skeletal myocyte apoptosis as a mechanism in the development of sarcopenia and reports supporting myonuclear apoptosis as a target for interventions against age-related muscle loss. Results: Advanced age is associated with increased signaling through extrinsic and intrinsic apoptotic pathways in skeletal myocytes. In contrast, downregulation of myocyte apoptosis through calorie restriction, exercise training, hormonal supplementation, drugs (e.g. angiotensin-converting enzyme inhibitors, acetaminophen, antimyostatin antibodies), nutraceuticals or genetic interventions (e.g. PGC-1α overexpression) is linked with preservation of muscle integrity and improved physical performance in late life. Preliminary data also indicate that skeletal myocyte apoptotic signaling may be downregulated by compounds, such as resveratrol, with calorie restriction-mimicking properties. Whether exercise mimetics exert a similar effect has not yet been investigated. Conclusions: Available evidence suggests that targeting myonuclear apoptosis might provide novel and effective therapeutic tools to combat sarcopenia. Further research is required to definitely establish if downregulating myonuclear apoptosis is effective in maintaining muscle mass and function in late life, identify the most relevant apoptotic pathway(s) to target, and determine the optimal timing for intervening.
AbstractList Background: Sarcopenia, the age-related loss of muscle mass and function, represents a relevant public health issue due to its high prevalence and detrimental consequences. While the exact mechanisms underlying the pathogenesis of sarcopenia are not clear, growing experimental evidence indicates that progressive myonuclear elimination over the course of aging via an apoptosis-like process may represent a converging mechanism through which muscle atrophy and loss of physical function develop. Notably, the proapoptotic environment taking place in aged muscle appears amenable to interventions. Objective: We aimed at providing (1) an overview of signaling pathways of apoptosis relevant to sarcopenia, and (2) a review of the literature supporting myocyte apoptosis as a target for interventions against muscle aging. Methods: We summarized findings from studies focused on skeletal myocyte apoptosis as a mechanism in the development of sarcopenia and reports supporting myonuclear apoptosis as a target for interventions against age-related muscle loss. Results: Advanced age is associated with increased signaling through extrinsic and intrinsic apoptotic pathways in skeletal myocytes. In contrast, downregulation of myocyte apoptosis through calorie restriction, exercise training, hormonal supplementation, drugs (e.g. angiotensin-converting enzyme inhibitors, acetaminophen, antimyostatin antibodies), nutraceuticals or genetic interventions (e.g. PGC-1α overexpression) is linked with preservation of muscle integrity and improved physical performance in late life. Preliminary data also indicate that skeletal myocyte apoptotic signaling may be downregulated by compounds, such as resveratrol, with calorie restriction-mimicking properties. Whether exercise mimetics exert a similar effect has not yet been investigated. Conclusions: Available evidence suggests that targeting myonuclear apoptosis might provide novel and effective therapeutic tools to combat sarcopenia. Further research is required to definitely establish if downregulating myonuclear apoptosis is effective in maintaining muscle mass and function in late life, identify the most relevant apoptotic pathway(s) to target, and determine the optimal timing for intervening.
Background: Sarcopenia, the age-related loss of muscle mass and function, represents a relevant public health issue due to its high prevalence and detrimental consequences. While the exact mechanisms underlying the pathogenesis of sarcopenia are not clear, growing experimental evidence indicates that progressive myonuclear elimination over the course of aging via an apoptosis-like process may represent a converging mechanism through which muscle atrophy and loss of physical function develop. Notably, the proapoptotic environment taking place in aged muscle appears amenable to interventions. Objective: We aimed at providing (1) an overview of signaling pathways of apoptosis relevant to sarcopenia, and (2) a review of the literature supporting myocyte apoptosis as a target for interventions against muscle aging. Methods: We summarized findings from studies focused on skeletal myocyte apoptosis as a mechanism in the development of sarcopenia and reports supporting myonuclear apoptosis as a target for interventions against age-related muscle loss. Results: Advanced age is associated with increased signaling through extrinsic and intrinsic apoptotic pathways in skeletal myocytes. In contrast, downregulation of myocyte apoptosis through calorie restriction, exercise training, hormonal supplementation, drugs (e.g. angiotensin-converting enzyme inhibitors, acetaminophen, antimyostatin antibodies), nutraceuticals or genetic interventions (e.g. PGC-1α overexpression) is linked with preservation of muscle integrity and improved physical performance in late life. Preliminary data also indicate that skeletal myocyte apoptotic signaling may be downregulated by compounds, such as resveratrol, with calorie restriction-mimicking properties. Whether exercise mimetics exert a similar effect has not yet been investigated. Conclusions: Available evidence suggests that targeting myonuclear apoptosis might provide novel and effective therapeutic tools to combat sarcopenia. Further research is required to definitely establish if downregulating myonuclear apoptosis is effective in maintaining muscle mass and function in late life, identify the most relevant apoptotic pathway(s) to target, and determine the optimal timing for intervening.[PUBLICATION ABSTRACT]
Sarcopenia, the age-related loss of muscle mass and function, represents a relevant public health issue due to its high prevalence and detrimental consequences. While the exact mechanisms underlying the pathogenesis of sarcopenia are not clear, growing experimental evidence indicates that progressive myonuclear elimination over the course of aging via an apoptosis-like process may represent a converging mechanism through which muscle atrophy and loss of physical function develop. Notably, the proapoptotic environment taking place in aged muscle appears amenable to interventions.BACKGROUNDSarcopenia, the age-related loss of muscle mass and function, represents a relevant public health issue due to its high prevalence and detrimental consequences. While the exact mechanisms underlying the pathogenesis of sarcopenia are not clear, growing experimental evidence indicates that progressive myonuclear elimination over the course of aging via an apoptosis-like process may represent a converging mechanism through which muscle atrophy and loss of physical function develop. Notably, the proapoptotic environment taking place in aged muscle appears amenable to interventions.We aimed at providing (1) an overview of signaling pathways of apoptosis relevant to sarcopenia, and (2) a review of the literature supporting myocyte apoptosis as a target for interventions against muscle aging.OBJECTIVEWe aimed at providing (1) an overview of signaling pathways of apoptosis relevant to sarcopenia, and (2) a review of the literature supporting myocyte apoptosis as a target for interventions against muscle aging.We summarized findings from studies focused on skeletal myocyte apoptosis as a mechanism in the development of sarcopenia and reports supporting myonuclear apoptosis as a target for interventions against age-related muscle loss.METHODSWe summarized findings from studies focused on skeletal myocyte apoptosis as a mechanism in the development of sarcopenia and reports supporting myonuclear apoptosis as a target for interventions against age-related muscle loss.Advanced age is associated with increased signaling through extrinsic and intrinsic apoptotic pathways in skeletal myocytes. In contrast, downregulation of myocyte apoptosis through calorie restriction, exercise training, hormonal supplementation, drugs (e.g. angiotensin-converting enzyme inhibitors, acetaminophen, antimyostatin antibodies), nutraceuticals or genetic interventions (e.g. PGC-1α overexpression) is linked with preservation of muscle integrity and improved physical performance in late life. Preliminary data also indicate that skeletal myocyte apoptotic signaling may be downregulated by compounds, such as resveratrol, with calorie restriction-mimicking properties. Whether exercise mimetics exert a similar effect has not yet been investigated.RESULTSAdvanced age is associated with increased signaling through extrinsic and intrinsic apoptotic pathways in skeletal myocytes. In contrast, downregulation of myocyte apoptosis through calorie restriction, exercise training, hormonal supplementation, drugs (e.g. angiotensin-converting enzyme inhibitors, acetaminophen, antimyostatin antibodies), nutraceuticals or genetic interventions (e.g. PGC-1α overexpression) is linked with preservation of muscle integrity and improved physical performance in late life. Preliminary data also indicate that skeletal myocyte apoptotic signaling may be downregulated by compounds, such as resveratrol, with calorie restriction-mimicking properties. Whether exercise mimetics exert a similar effect has not yet been investigated.Available evidence suggests that targeting myonuclear apoptosis might provide novel and effective therapeutic tools to combat sarcopenia. Further research is required to definitely establish if downregulating myonuclear apoptosis is effective in maintaining muscle mass and function in late life, identify the most relevant apoptotic pathway(s) to target, and determine the optimal timing for intervening.CONCLUSIONSAvailable evidence suggests that targeting myonuclear apoptosis might provide novel and effective therapeutic tools to combat sarcopenia. Further research is required to definitely establish if downregulating myonuclear apoptosis is effective in maintaining muscle mass and function in late life, identify the most relevant apoptotic pathway(s) to target, and determine the optimal timing for intervening.
Background: Sarcopenia, the age-related loss of muscle mass and function, represents a relevant public health issue due to its high prevalence and detrimental consequences. While the exact mechanisms underlying the pathogenesis of sarcopenia are not clear, growing experimental evidence indicates that progressive myonuclear elimination over the course of aging via an apoptosis-like process may represent a converging mechanism through which muscle atrophy and loss of physical function develop. Notably, the proapoptotic environment taking place in aged muscle appears amenable to interventions. Objective: We aimed at providing (1) an overview of signaling pathways of apoptosis relevant to sarcopenia, and (2) a review of the literature supporting myocyte apoptosis as a target for interventions against muscle aging. Methods: We summarized findings from studies focused on skeletal myocyte apoptosis as a mechanism in the development of sarcopenia and reports supporting myonuclear apoptosis as a target for interventions against age-related muscle loss. Results: Advanced age is associated with increased signaling through extrinsic and intrinsic apoptotic pathways in skeletal myocytes. In contrast, downregulation of myocyte apoptosis through calorie restriction, exercise training, hormonal supplementation, drugs (e.g. angiotensin-converting enzyme inhibitors, acetaminophen, antimyostatin antibodies), nutraceuticals or genetic interventions (e.g. PGC-1 alpha overexpression) is linked with preservation of muscle integrity and improved physical performance in late life. Preliminary data also indicate that skeletal myocyte apoptotic signaling may be downregulated by compounds, such as resveratrol, with calorie restriction-mimicking properties. Whether exercise mimetics exert a similar effect has not yet been investigated. Conclusions: Available evidence suggests that targeting myonuclear apoptosis might provide novel and effective therapeutic tools to combat sarcopenia. Further research is required to definitely establish if downregulating myonuclear apoptosis is effective in maintaining muscle mass and function in late life, identify the most relevant apoptotic pathway(s) to target, and determine the optimal timing for intervening. Copyright [copy 2011 S. Karger AG, Basel
Sarcopenia, the age-related loss of muscle mass and function, represents a relevant public health issue due to its high prevalence and detrimental consequences. While the exact mechanisms underlying the pathogenesis of sarcopenia are not clear, growing experimental evidence indicates that progressive myonuclear elimination over the course of aging via an apoptosis-like process may represent a converging mechanism through which muscle atrophy and loss of physical function develop. Notably, the proapoptotic environment taking place in aged muscle appears amenable to interventions. We aimed at providing (1) an overview of signaling pathways of apoptosis relevant to sarcopenia, and (2) a review of the literature supporting myocyte apoptosis as a target for interventions against muscle aging. We summarized findings from studies focused on skeletal myocyte apoptosis as a mechanism in the development of sarcopenia and reports supporting myonuclear apoptosis as a target for interventions against age-related muscle loss. Advanced age is associated with increased signaling through extrinsic and intrinsic apoptotic pathways in skeletal myocytes. In contrast, downregulation of myocyte apoptosis through calorie restriction, exercise training, hormonal supplementation, drugs (e.g. angiotensin-converting enzyme inhibitors, acetaminophen, antimyostatin antibodies), nutraceuticals or genetic interventions (e.g. PGC-1α overexpression) is linked with preservation of muscle integrity and improved physical performance in late life. Preliminary data also indicate that skeletal myocyte apoptotic signaling may be downregulated by compounds, such as resveratrol, with calorie restriction-mimicking properties. Whether exercise mimetics exert a similar effect has not yet been investigated. Available evidence suggests that targeting myonuclear apoptosis might provide novel and effective therapeutic tools to combat sarcopenia. Further research is required to definitely establish if downregulating myonuclear apoptosis is effective in maintaining muscle mass and function in late life, identify the most relevant apoptotic pathway(s) to target, and determine the optimal timing for intervening.
Author Calvani, Riccardo
Leeuwenburgh, Christiaan
Bernabei, Roberto
Marzetti, Emanuele
AuthorAffiliation c Department of Department of Aging and Geriatric Research, Institute on Aging, University of Florida, Gainesville, Fla., USA
b Department of Gerontology, Geriatrics and Physiatrics, University Hospital Agostino Gemelli, Catholic University of the Sacred Heart, Rome, Italy
a Department of Orthopaedics and Traumatology University Hospital Agostino Gemelli, Catholic University of the Sacred Heart, Rome, Italy
AuthorAffiliation_xml – name: a Department of Orthopaedics and Traumatology University Hospital Agostino Gemelli, Catholic University of the Sacred Heart, Rome, Italy
– name: b Department of Gerontology, Geriatrics and Physiatrics, University Hospital Agostino Gemelli, Catholic University of the Sacred Heart, Rome, Italy
– name: c Department of Department of Aging and Geriatric Research, Institute on Aging, University of Florida, Gainesville, Fla., USA
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  surname: Marzetti
  fullname: Marzetti, Emanuele
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  surname: Calvani
  fullname: Calvani, Riccardo
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  givenname: Roberto
  surname: Bernabei
  fullname: Bernabei, Roberto
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  givenname: Christiaan
  surname: Leeuwenburgh
  fullname: Leeuwenburgh, Christiaan
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https://www.ncbi.nlm.nih.gov/pubmed/21952604$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Copyright 2011 S. Karger AG, Basel
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Copyright (c) 2012 S. Karger AG, Basel
Copyright © 2011 by S. Karger AG, Basel 2011
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Issue 2
Keywords Angiotensin-converting enzyme inhibitors
Mitochondria
Exercise
Calorie restriction
Resveratrol
Muscle
Hormones
Physical exercise
Senescence
Enzyme inhibitor
Review
Antioxidant
Striated muscle
Stilbene derivatives
Myocyte
Sarcopenia
Renin angiotensin system
Vertebrata
Mammalia
Angiotensin
Apoptosis
Language English
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  year: 2012
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PublicationTitle Gerontology (Basel)
PublicationTitleAlternate Gerontology
PublicationYear 2012
Publisher Karger
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References 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;36:27–39.1473228810.1016%2Fj.freeradbiomed.2003.10.003
Marzetti E, Wohlgemuth SE, Lees HA, Chung HY, Giovannini S, Leeuwenburgh C: Age-related activation of mitochondrial caspase-independent apoptotic signaling in rat gastrocnemius muscle. Mech Ageing Dev 2008;129:542–549.10.1016%2Fj.mad.2008.05.005
Argiles JM, Lopez-Soriano FJ, Busquets S: Apoptosis signalling is essential and precedes protein degradation in wasting skeletal muscle during catabolic conditions. Int J Biochem Cell Biol 2008;40:1674–1678.10.1016%2Fj.biocel.2008.02.001
Safdar A, Bourgeois JM, Ogborn DI, Little JP, Hettinga BP, Akhtar M, Thompson JE, Melov S, Mocellin NJ, Kujoth GC, Prolla TA, Tarnopolsky MA: Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice. Proc Natl Acad Sci USA 2011;108:4135–4140.10.1073%2Fpnas.1019581108
Narkar VA, Downes M, Yu RT, Embler E, Wang YX, Banayo E, Mihaylova MM, Nelson MC, Zou Y, Juguilon H, Kang H, Shaw RJ, Evans RM: AMPK and PPARdelta agonists are exercise mimetics. Cell 2008;134:405–415.1867480910.1016%2Fj.cell.2008.06.051
Frankel JE, Bean JF, Frontera WR: Exercise in the elderly: research and clinical practice. Clin Geriatr Med 2006;22:239–256.10.1016%2Fj.cger.2005.12.002
Ekhterae D, Lin Z, Lundberg MS, Crow MT, Brosius FC, III, Nunez G: ARC inhibits cytochrome c release from mitochondria and protects against hypoxia-induced apoptosis in heart-derived H9c2 cells. Circ Res 1999;85:e70–e77.
Walston J, Fedarko N, Yang H, Leng S, Beamer B, Espinoza S, Lipton A, Zheng H, Becker K: The physical and biological characterization of a frail mouse model. J Gerontol A Biol Sci Med Sci 2008;63:391–398.10.1093%2Fgerona%2F63.4.391
Phillips T, Leeuwenburgh C: Muscle fiber specific apoptosis and TNF-alpha signaling in sarcopenia are attenuated by life-long calorie restriction. FASEB J 2005;19:668–670.
Du J, Wang X, Miereles C, Bailey JL, Debigare R, Zheng B, Price SR, Mitch WE: Activation of caspase-3 is an initial step triggering accelerated muscle proteolysis in catabolic conditions. J Clin Invest 2004;113:115–123.14702115
Marzetti E, Privitera G, Simili V, Wohlgemuth SE, Aulisa L, Pahor M, Leeuwenburgh C: Multiple pathways to the same end: mechanisms of myonuclear apoptosis in sarcopenia of aging. Scientific World J 2010;10:340–349.10.1100%2Ftsw.2010.27
Chung S, Yao H, Caito S, Hwang JW, Arunachalam G, Rahman I: Regulation of SIRT1 in cellular functions: role of polyphenols. Arch Biochem Biophys 2010;501:79–90.10.1016%2Fj.abb.2010.05.003
Kujoth GC, Leeuwenburgh C, Prolla TA: Mitochondrial DNA mutations and apoptosis in mammalian aging. Cancer Res 2006;66:7386–7389.10.1158%2F0008-5472.CAN-05-4670
Marzetti E, Carter CS, Wohlgemuth SE, Lees HA, Giovannini S, Anderson B, Quinn LS, Leeuwenburgh C: Changes in IL-15 expression and death-receptor apoptotic signaling in rat gastrocnemius muscle with aging and life-long calorie restriction. Mech Ageing Dev 2009;130:272–280.10.1016%2Fj.mad.2008.12.008
Wenz T, Rossi SG, Rotundo RL, Spiegelman BM, Moraes CT: Increased muscle PGC-1alpha expression protects from sarcopenia and metabolic disease during aging. Proc Natl Acad Sci USA 2009;106:20405–20410.1991807510.1073%2Fpnas.0911570106
Kerr JF, Wyllie AH, Currie AR: Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972;26:239–257.456102710.1038%2Fbjc.1972.33
Fiatarone MA, O’Neill EF, Ryan ND, Clements KM, Solares GR, Nelson ME, Roberts SB, Kehayias JJ, Lipsitz LA, Evans WJ: Exercise training and nutritional supplementation for physical frailty in very elderly people. N Engl J Med 1994;330:1769–1775.819015210.1056%2FNEJM199406233302501
Siddiqui MA, Kashyap MP, Kumar V, Al-Khedhairy AA, Musarrat J, Pant AB: Protective potential of trans-resveratrol against 4-hydroxynonenal induced damage in PC12 cells. Toxicol In Vitro 2010;24:1592–1598.10.1016%2Fj.tiv.2010.06.008
Marzetti E, Hwang JC, Lees HA, Wohlgemuth SE, Dupont-Versteegden EE, Carter CS, Bernabei R, Leeuwenburgh C: Mitochondrial death effectors: relevance to sarcopenia and disuse muscle atrophy. Biochim Biophys Acta 2010;1800:235–244.10.1016%2Fj.bbagen.2009.05.007
Xu J, Seo AY, Vorobyeva DA, Carter CS, Anton SD, Lezza AM, Leeuwenburgh C: Beneficial effects of a Q-ter based nutritional mixture on functional performance, mitochondrial function, and oxidative stress in rats. PLoS One 2010;5:e10572.10.1371%2Fjournal.pone.0010572
Landi F, Zuccala G, Gambassi G, Incalzi RA, Manigrasso L, Pagano F, Carbonin P, Bernabei R: Body mass index and mortality among older people living in the community. J Am Geriatr Soc 1999;47:1072–1076.10484248
Song W, Kwak HB, Lawler JM: Exercise training attenuates age-induced changes in apoptotic signaling in rat skeletal muscle. Antioxid Redox Signal 2006;8:517–528.10.1089%2Fars.2006.8.517
Turpin SM, Lancaster GI, Darby I, Febbraio MA, Watt MJ: Apoptosis in skeletal muscle myotubes is induced by ceramides and is positively related to insulin resistance. Am J Physiol Endocrinol Metab 2006;291:E1341–E1350.10.1152%2Fajpendo.00095.2006
Murphy KT, Koopman R, Naim T, Leger B, Trieu J, Ibebunjo C, Lynch GS: Antibody-directed myostatin inhibition in 21-mo-old mice reveals novel roles for myostatin signaling in skeletal muscle structure and function. FASEB J 2010;24:4433–4442.10.1096%2Ffj.10-159608
Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, Martin FC, Michel JP, Rolland Y, Schneider SM, Topinkova E, Vandewoude M, Zamboni M: Sarcopenia: European consensus on definition and diagnosis: report of the European Working Group on Sarcopenia in Older People. Age Ageing 2010;39:412–423.10.1093%2Fageing%2Fafq034
Carter CS, Giovaninni S, Seo DO, Dupree J, Morgan D, Chung HY, Lees H, Daniels M, Hubbard GB, Lee S, Ikeno Y, Foster TC, Buford TW, Marzetti E: Differential effects of enalapril and losartan on body composition and indices of muscle quality in aged male Fischer 344 × Brown Norway rats. Age (Dordr) 2011;33:167–183.10.1007%2Fs11357-010-9196-y
Roubenoff R: Sarcopenia: a major modifiable cause of frailty in the elderly. J Nutr Health Aging 2000;4:140–142.
Jang YC, Lustgarten MS, Liu Y, Muller FL, Bhattacharya A, Liang H, Salmon AB, Brooks SV, Larkin L, Hayworth CR, Richardson A, Van RH: Increased superoxide in vivo accelerates age-associated muscle atrophy through mitochondrial dysfunction and neuromuscular junction degeneration. FASEB J 2010;24:1376–1390.10.1096%2Ffj.09-146308
Zimmermann KC, Bonzon C, Green DR: The machinery of programmed cell death. Pharmacol Ther 2001;92:57–70.10.1016%2FS0163-7258%2801%2900159-0
Marzetti E, Groban L, Wohlgemuth SE, Lees HA, Lin M, Jobe H, Giovannini S, Leeuwenburgh C, Carter CS: Effects of short-term GH supplementation and treadmill exercise training on physical performance and skeletal muscle apoptosis in old rats. Am J Physiol Regul Integr Comp Physiol 2008;294: R558–R567.10.1152%2Fajpregu.00620.2007
Parsons MJ, Green DR: Mitochondria in cell death. Essays Biochem 2010;47:99–114.10.1042%2Fbse0470099
Kovacheva EL, Hikim AP, Shen R, Sinha I, Sinha-Hikim I: Testosterone supplementation reverses sarcopenia in aging through regulation of myostatin, c-Jun NH2-terminal kinase, Notch, and Akt signaling pathways. Endocrinology 2010;151:628–638.10.1210%2Fen.2009-1177
Pistilli EE, Alway SE: Systemic elevation of interleukin-15 in vivo promotes apoptosis in skeletal muscles of young adult and aged rats. Biochem Biophys Res Commun 2008;373:20–24.10.1016%2Fj.bbrc.2008.05.188
Jackson JR, Ryan MJ, Hao Y, Alway SE: Mediation of endogenous antioxidant enzymes and apoptotic signaling by resveratrol following muscle disuse in the gastrocnemius muscles of young and old rats. Am J Physiol Regul Integr Comp Physiol 2010;299:R1572–R1581.10.1152%2Fajpregu.00489.2010
Wu M, Katta A, Gadde MK, Liu H, Kakarla SK, Fannin J, Paturi S, Arvapalli RK, Rice KM, Wang Y, Blough ER: Aging-associated dysfunction of Akt/protein kinase B: S-nitrosylation and acetaminophen intervention. PLoS One 2009;4:e6430.10.1371%2Fjournal.pone.0006430
Marzetti E, Lees HA, Wohlgemuth SE, Leeuwenburgh C: Sarcopenia of aging: underlying cellular mechanisms and protection by calorie restriction. Bio Factors 2009;35:28–35.1931984310.1002%2Fbiof.5
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References_xml – reference: Marzetti E, Privitera G, Simili V, Wohlgemuth SE, Aulisa L, Pahor M, Leeuwenburgh C: Multiple pathways to the same end: mechanisms of myonuclear apoptosis in sarcopenia of aging. Scientific World J 2010;10:340–349.10.1100%2Ftsw.2010.27
– reference: Kerr JF, Wyllie AH, Currie AR: Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972;26:239–257.456102710.1038%2Fbjc.1972.33
– reference: Parsons MJ, Green DR: Mitochondria in cell death. Essays Biochem 2010;47:99–114.10.1042%2Fbse0470099
– reference: Marzetti E, Carter CS, Wohlgemuth SE, Lees HA, Giovannini S, Anderson B, Quinn LS, Leeuwenburgh C: Changes in IL-15 expression and death-receptor apoptotic signaling in rat gastrocnemius muscle with aging and life-long calorie restriction. Mech Ageing Dev 2009;130:272–280.10.1016%2Fj.mad.2008.12.008
– reference: Du J, Wang X, Miereles C, Bailey JL, Debigare R, Zheng B, Price SR, Mitch WE: Activation of caspase-3 is an initial step triggering accelerated muscle proteolysis in catabolic conditions. J Clin Invest 2004;113:115–123.14702115
– reference: Turpin SM, Lancaster GI, Darby I, Febbraio MA, Watt MJ: Apoptosis in skeletal muscle myotubes is induced by ceramides and is positively related to insulin resistance. Am J Physiol Endocrinol Metab 2006;291:E1341–E1350.10.1152%2Fajpendo.00095.2006
– reference: Wenz T, Rossi SG, Rotundo RL, Spiegelman BM, Moraes CT: Increased muscle PGC-1alpha expression protects from sarcopenia and metabolic disease during aging. Proc Natl Acad Sci USA 2009;106:20405–20410.1991807510.1073%2Fpnas.0911570106
– reference: Argiles JM, Lopez-Soriano FJ, Busquets S: Apoptosis signalling is essential and precedes protein degradation in wasting skeletal muscle during catabolic conditions. Int J Biochem Cell Biol 2008;40:1674–1678.10.1016%2Fj.biocel.2008.02.001
– reference: Jackson JR, Ryan MJ, Hao Y, Alway SE: Mediation of endogenous antioxidant enzymes and apoptotic signaling by resveratrol following muscle disuse in the gastrocnemius muscles of young and old rats. Am J Physiol Regul Integr Comp Physiol 2010;299:R1572–R1581.10.1152%2Fajpregu.00489.2010
– reference: Kujoth GC, Leeuwenburgh C, Prolla TA: Mitochondrial DNA mutations and apoptosis in mammalian aging. Cancer Res 2006;66:7386–7389.10.1158%2F0008-5472.CAN-05-4670
– reference: Marzetti E, Wohlgemuth SE, Lees HA, Chung HY, Giovannini S, Leeuwenburgh C: Age-related activation of mitochondrial caspase-independent apoptotic signaling in rat gastrocnemius muscle. Mech Ageing Dev 2008;129:542–549.10.1016%2Fj.mad.2008.05.005
– reference: Zimmermann KC, Bonzon C, Green DR: The machinery of programmed cell death. Pharmacol Ther 2001;92:57–70.10.1016%2FS0163-7258%2801%2900159-0
– reference: Xu J, Seo AY, Vorobyeva DA, Carter CS, Anton SD, Lezza AM, Leeuwenburgh C: Beneficial effects of a Q-ter based nutritional mixture on functional performance, mitochondrial function, and oxidative stress in rats. PLoS One 2010;5:e10572.10.1371%2Fjournal.pone.0010572
– reference: Chung S, Yao H, Caito S, Hwang JW, Arunachalam G, Rahman I: Regulation of SIRT1 in cellular functions: role of polyphenols. Arch Biochem Biophys 2010;501:79–90.10.1016%2Fj.abb.2010.05.003
– reference: Ekhterae D, Lin Z, Lundberg MS, Crow MT, Brosius FC, III, Nunez G: ARC inhibits cytochrome c release from mitochondria and protects against hypoxia-induced apoptosis in heart-derived H9c2 cells. Circ Res 1999;85:e70–e77.
– reference: Marzetti E, Groban L, Wohlgemuth SE, Lees HA, Lin M, Jobe H, Giovannini S, Leeuwenburgh C, Carter CS: Effects of short-term GH supplementation and treadmill exercise training on physical performance and skeletal muscle apoptosis in old rats. Am J Physiol Regul Integr Comp Physiol 2008;294: R558–R567.10.1152%2Fajpregu.00620.2007
– reference: Murphy KT, Koopman R, Naim T, Leger B, Trieu J, Ibebunjo C, Lynch GS: Antibody-directed myostatin inhibition in 21-mo-old mice reveals novel roles for myostatin signaling in skeletal muscle structure and function. FASEB J 2010;24:4433–4442.10.1096%2Ffj.10-159608
– reference: Song W, Kwak HB, Lawler JM: Exercise training attenuates age-induced changes in apoptotic signaling in rat skeletal muscle. Antioxid Redox Signal 2006;8:517–528.10.1089%2Fars.2006.8.517
– reference: Roubenoff R: Sarcopenia: a major modifiable cause of frailty in the elderly. J Nutr Health Aging 2000;4:140–142.
– reference: Frankel JE, Bean JF, Frontera WR: Exercise in the elderly: research and clinical practice. Clin Geriatr Med 2006;22:239–256.10.1016%2Fj.cger.2005.12.002
– reference: Narkar VA, Downes M, Yu RT, Embler E, Wang YX, Banayo E, Mihaylova MM, Nelson MC, Zou Y, Juguilon H, Kang H, Shaw RJ, Evans RM: AMPK and PPARdelta agonists are exercise mimetics. Cell 2008;134:405–415.1867480910.1016%2Fj.cell.2008.06.051
– reference: Wu M, Katta A, Gadde MK, Liu H, Kakarla SK, Fannin J, Paturi S, Arvapalli RK, Rice KM, Wang Y, Blough ER: Aging-associated dysfunction of Akt/protein kinase B: S-nitrosylation and acetaminophen intervention. PLoS One 2009;4:e6430.10.1371%2Fjournal.pone.0006430
– reference: 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;36:27–39.1473228810.1016%2Fj.freeradbiomed.2003.10.003
– reference: Marzetti E, Lees HA, Wohlgemuth SE, Leeuwenburgh C: Sarcopenia of aging: underlying cellular mechanisms and protection by calorie restriction. Bio Factors 2009;35:28–35.1931984310.1002%2Fbiof.5
– reference: Kovacheva EL, Hikim AP, Shen R, Sinha I, Sinha-Hikim I: Testosterone supplementation reverses sarcopenia in aging through regulation of myostatin, c-Jun NH2-terminal kinase, Notch, and Akt signaling pathways. Endocrinology 2010;151:628–638.10.1210%2Fen.2009-1177
– reference: Phillips T, Leeuwenburgh C: Muscle fiber specific apoptosis and TNF-alpha signaling in sarcopenia are attenuated by life-long calorie restriction. FASEB J 2005;19:668–670.
– reference: Landi F, Zuccala G, Gambassi G, Incalzi RA, Manigrasso L, Pagano F, Carbonin P, Bernabei R: Body mass index and mortality among older people living in the community. J Am Geriatr Soc 1999;47:1072–1076.10484248
– reference: Siddiqui MA, Kashyap MP, Kumar V, Al-Khedhairy AA, Musarrat J, Pant AB: Protective potential of trans-resveratrol against 4-hydroxynonenal induced damage in PC12 cells. Toxicol In Vitro 2010;24:1592–1598.10.1016%2Fj.tiv.2010.06.008
– reference: Fiatarone MA, O’Neill EF, Ryan ND, Clements KM, Solares GR, Nelson ME, Roberts SB, Kehayias JJ, Lipsitz LA, Evans WJ: Exercise training and nutritional supplementation for physical frailty in very elderly people. N Engl J Med 1994;330:1769–1775.819015210.1056%2FNEJM199406233302501
– reference: Jang YC, Lustgarten MS, Liu Y, Muller FL, Bhattacharya A, Liang H, Salmon AB, Brooks SV, Larkin L, Hayworth CR, Richardson A, Van RH: Increased superoxide in vivo accelerates age-associated muscle atrophy through mitochondrial dysfunction and neuromuscular junction degeneration. FASEB J 2010;24:1376–1390.10.1096%2Ffj.09-146308
– reference: Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, Martin FC, Michel JP, Rolland Y, Schneider SM, Topinkova E, Vandewoude M, Zamboni M: Sarcopenia: European consensus on definition and diagnosis: report of the European Working Group on Sarcopenia in Older People. Age Ageing 2010;39:412–423.10.1093%2Fageing%2Fafq034
– reference: Marzetti E, Hwang JC, Lees HA, Wohlgemuth SE, Dupont-Versteegden EE, Carter CS, Bernabei R, Leeuwenburgh C: Mitochondrial death effectors: relevance to sarcopenia and disuse muscle atrophy. Biochim Biophys Acta 2010;1800:235–244.10.1016%2Fj.bbagen.2009.05.007
– reference: Pistilli EE, Alway SE: Systemic elevation of interleukin-15 in vivo promotes apoptosis in skeletal muscles of young adult and aged rats. Biochem Biophys Res Commun 2008;373:20–24.10.1016%2Fj.bbrc.2008.05.188
– reference: Safdar A, Bourgeois JM, Ogborn DI, Little JP, Hettinga BP, Akhtar M, Thompson JE, Melov S, Mocellin NJ, Kujoth GC, Prolla TA, Tarnopolsky MA: Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice. Proc Natl Acad Sci USA 2011;108:4135–4140.10.1073%2Fpnas.1019581108
– reference: Carter CS, Giovaninni S, Seo DO, Dupree J, Morgan D, Chung HY, Lees H, Daniels M, Hubbard GB, Lee S, Ikeno Y, Foster TC, Buford TW, Marzetti E: Differential effects of enalapril and losartan on body composition and indices of muscle quality in aged male Fischer 344 × Brown Norway rats. Age (Dordr) 2011;33:167–183.10.1007%2Fs11357-010-9196-y
– reference: Walston J, Fedarko N, Yang H, Leng S, Beamer B, Espinoza S, Lipton A, Zheng H, Becker K: The physical and biological characterization of a frail mouse model. J Gerontol A Biol Sci Med Sci 2008;63:391–398.10.1093%2Fgerona%2F63.4.391
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Snippet Background: Sarcopenia, the age-related loss of muscle mass and function, represents a relevant public health issue due to its high prevalence and detrimental...
Sarcopenia, the age-related loss of muscle mass and function, represents a relevant public health issue due to its high prevalence and detrimental...
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Index Database
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StartPage 99
SubjectTerms Age
Age differences
Aged
Aging
Animals
Antibodies
Apoptosis
Apoptosis - drug effects
Apoptosis - genetics
Apoptosis - physiology
Atrophy
Biological and medical sciences
Caloric Restriction
Cell Nucleus - pathology
Cells
Clinical Section / Mini-Review
Development. Metamorphosis. Moult. Ageing
Diet
Drug therapy
Drugs
Elimination
Exercise
Exercise Therapy
Frail Elderly
Frailty
Function
Fundamental and applied biological sciences. Psychology
Genetics
Hormones
Humans
Intervention
Literature reviews
Models, Biological
Morality
Muscle Fibers, Skeletal - drug effects
Muscle Fibers, Skeletal - pathology
Muscle Fibers, Skeletal - physiology
Musculoskeletal diseases
Novels
Physical ability
Preservation
Property
Public health
Sarcopenia
Sarcopenia - pathology
Sarcopenia - physiopathology
Sarcopenia - prevention & control
Sarcopenia - therapy
Signal Transduction - physiology
Signaling
Vertebrates: anatomy and physiology, studies on body, several organs or systems
Title Apoptosis in Skeletal Myocytes: A Potential Target for Interventions against Sarcopenia and Physical Frailty – A Mini-Review
URI https://karger.com/doi/10.1159/000330064
https://www.ncbi.nlm.nih.gov/pubmed/21952604
https://www.proquest.com/docview/1013527553
https://www.proquest.com/docview/1492628510
https://www.proquest.com/docview/926150994
https://pubmed.ncbi.nlm.nih.gov/PMC7077073
Volume 58
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