心脏老化以及预防机制研究的新进展
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摘要
进行性心肌细胞肥大、炎症和心脏纤维化的逐渐发展是心脏衰老的标志。现概述心脏衰老中表现出的临床和细胞变化,以及维持体内平衡和延缓衰老的机制,这些机制包括自噬、泛素介导的蛋白质降解、细胞凋亡、线粒体稳态和心脏基质稳态并讨论心脏老化的干预措施,这些措施包括热量限制、雷帕霉素、白藜芦醇、生长分化因子-11和线粒体抗氧化剂等治疗剂。对干预措施的深入研究有望进一步改进治疗方式。
The progressive development of cardiomyocyte hypertrophy,inflammation and cardiac fibrosis is a hallmark of cardiac aging. This review outlines the clinical and cellular changes demonstrated during cardiac aging,and the mechanisms that maintain homeostasis and delay aging. These mechanisms include autophagy,ubiquitin-mediated protein degradation,apoptosis,mitochondrial homeostasis,and cardiac matrix homeostasis. Finally,the intervention measures of heart aging are discussed. These include calorie restriction,rapamycin,resveratrol,growth differentiation factor 11 and mitochondrial antioxidants. Further research into interventions is expected to improve the treatment.
The progressive development of cardiomyocyte hypertrophy,inflammation and cardiac fibrosis is a hallmark of cardiac aging. This review outlines the clinical and cellular changes demonstrated during cardiac aging,and the mechanisms that maintain homeostasis and delay aging. These mechanisms include autophagy,ubiquitin-mediated protein degradation,apoptosis,mitochondrial homeostasis,and cardiac matrix homeostasis. Finally,the intervention measures of heart aging are discussed. These include calorie restriction,rapamycin,resveratrol,growth differentiation factor 11 and mitochondrial antioxidants. Further research into interventions is expected to improve the treatment.
引文
[1]Zhu Q,Wang XB,Yao Y,et al.Association between anthropometric measures and cardiovascular disease(CVD)risk factors in Hainan centenarians:investigation based on the Centenarian's health study[J].BMC Cardiovasc Disord,2018,18(1):73.
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[14]Koga H,Kaushik S,Cuervo AM.Protein homeostasis and aging:the importance of exquisite quality control[J].Ageing Res Rev,2011,10:205-215.
[15]Korovila IM,Hugo JP,Castro,et al.Proteostasis,oxidative stress and aging[J].Redox Biol,2017,13:550-567.
[16]Dutta D,Xu J,Kim JS,et al.Upregulated autophagy protects cardiomyocytes from oxidative stress-induced toxicity[J].Autophagy,2013,9:328-344.
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[19]Meschiari CA,Ero OK,Pan H,et al.The impact of aging on cardiac extracellular matrix[J].Geroscience,2017,39(1):7-18.
[20]Speakman JR,Mitchell SE.Caloric restriction[J].Mol Aspects Med,2011,32:159-221.
[21]Dhabi JM,Tsuchiya T,Kim HJ,et al.Gene expression and physiologic responses of the heart to the initiation and withdrawal of caloric restriction[J].J Gerontol ABiol Sci Med Sci,2006,61:218-231.
[22]Dai DF,Karunadharma P,Chiao YA,et al.Altered proteome turnover and remodeling by short-term caloric restriction or rapamycin rejuvenate the aging heart[J].Aging Cell,2014,13:529-539.
[23]Wilkinson JE,Burmeister L,Brooks SV,et al.Rapamycin slows aging in mice[J].Aging Cell,2012,11:675-682.
[24]Flynn JM,O’Leary MN,Zambataro CA,et al.Late-life rapamycin treatment reverses age-related heart dysfunction[J].Aging Cell,2013,12:851-862.
[25]Pollack RM,Crandall JP.Resveratrol:therapeutic potential for improving cardiometabolic health[J].Am J Hypertens,2013,26(11):1260-1268.
[26]Loffredo FS,Steinhauser ML,Jay SM,et al.Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy[J].Cell,2013,153:828-839.
[27]Owada T,Yamauchi H,Saitoh SI,et al.Resolution of mitochondrial oxidant stress improves aged-cardiovascular performance[J].Coron Artery Dis,2017,28(1):33-43.
[2]Selim AJ,Fincke G,Berlowitz DR,et al.Comprehensive health status assessment of centenarians:results from the 1999 large health survey of veteran enrollees[J].J Gerontol A Biol Sci Med Sci,2005,60:515-519.
[3]Kheirbek RE,Fokar A,Shara N,et al.Characteristics and incidence of chronic illness in community-dwelling predominantly male U.S.veteran centenarians[J].Am Geriatr Soc,2017,65(9):2100-2106.
[4]Yashin AI,Akushevich IV,Arbeev KG,et al.Insights on aging and exceptional longevity from longitudinal data:novel findings from the Framingham Heart Study[J].Age(Dordr),2006,28:363-374.
[5]Dai DF,Rabinovitch PS.Cardiac aging in mice and humans:the role of mitochondrial oxidative stress[J].Trends Cardiovasc Med,2009,19:213-220.
[6]Bursi F,Weston SA,Redfield M,et al.Systolic and diastolic heart failure in the community[J].JAMA,2006,296:2209-2216.
[7]Correia LC,Lakatta EG,O’Connor FC,et al.Attenuated cardiovascular reserve during prolonged submaximal cycle exercise in healthy older subjects[J].J Am Coll Cardiol,2002,40:1290-1297.
[8]Lakatta EG.Arterial and cardiac aging:major shareholders in cardiovascular disease enterprises:partⅢ:cellular and molecular clues to heart and arterial aging[J].Circulation,2003,107:490-497.
[9]Karavidas A,Lazaros G,Tsiachris D,et al.Aging and the cardiovascular system[J].Hellenic J Cardiol,2010,51:421-427.
[10]Adegunsoye A,Mundkur M,Nanda NC,et al.Spectrum of calcific aortic valve disease:pathogenesis,disease progression,and treatment strategies[J].Echocardiography,2011,28(1):117-129.
[11]Correia LC,Lakatta EG,O’Connor FC,et al.Attenuated cardiovascular reserve during prolonged submaximal cycle exercise in healthy older subjects[J].J Am Coll Cardiol,2002,40:1290-1297.
[12]Johnson SC,Sangesland M,Kaeberlein M,et al.Modulating m TOR in aging and health[J].Interdiscip Gerontol,2015,40:107-127.
[13]Aunan JR,Cho WC,Sreide K.The biology of aging and cancer:a brief overview of shared and divergent molecular hallmarks[J].Aging Dis,2017,8(5):628-642.
[14]Koga H,Kaushik S,Cuervo AM.Protein homeostasis and aging:the importance of exquisite quality control[J].Ageing Res Rev,2011,10:205-215.
[15]Korovila IM,Hugo JP,Castro,et al.Proteostasis,oxidative stress and aging[J].Redox Biol,2017,13:550-567.
[16]Dutta D,Xu J,Kim JS,et al.Upregulated autophagy protects cardiomyocytes from oxidative stress-induced toxicity[J].Autophagy,2013,9:328-344.
[17]Pagan J,Seto T,Pagano M,et al.Role of the ubiquitin proteasome system in the heart[J].Circ Res,2013,112:1046-1058.
[18]Martín-Fernández B,Gredilla R.Mitochondria and oxidative stress in heart aging[J].Age(Dordr),2016,38(4):225-238.
[19]Meschiari CA,Ero OK,Pan H,et al.The impact of aging on cardiac extracellular matrix[J].Geroscience,2017,39(1):7-18.
[20]Speakman JR,Mitchell SE.Caloric restriction[J].Mol Aspects Med,2011,32:159-221.
[21]Dhabi JM,Tsuchiya T,Kim HJ,et al.Gene expression and physiologic responses of the heart to the initiation and withdrawal of caloric restriction[J].J Gerontol ABiol Sci Med Sci,2006,61:218-231.
[22]Dai DF,Karunadharma P,Chiao YA,et al.Altered proteome turnover and remodeling by short-term caloric restriction or rapamycin rejuvenate the aging heart[J].Aging Cell,2014,13:529-539.
[23]Wilkinson JE,Burmeister L,Brooks SV,et al.Rapamycin slows aging in mice[J].Aging Cell,2012,11:675-682.
[24]Flynn JM,O’Leary MN,Zambataro CA,et al.Late-life rapamycin treatment reverses age-related heart dysfunction[J].Aging Cell,2013,12:851-862.
[25]Pollack RM,Crandall JP.Resveratrol:therapeutic potential for improving cardiometabolic health[J].Am J Hypertens,2013,26(11):1260-1268.
[26]Loffredo FS,Steinhauser ML,Jay SM,et al.Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy[J].Cell,2013,153:828-839.
[27]Owada T,Yamauchi H,Saitoh SI,et al.Resolution of mitochondrial oxidant stress improves aged-cardiovascular performance[J].Coron Artery Dis,2017,28(1):33-43.