Cardiac aging: From molecular mechanisms to significance in human health and disease

Antioxidants and Redox Signaling

Volumn 16, Issue 12, 2012, Pages 1492-1536

  Dai, Dao Fu ^a   Chen, Tony ^a   Johnson, Simon C ^a   Szeto, Hazel ^b   Rabinovitch, Peter S ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA TOCOPHEROL; ATRIAL NATRIURETIC FACTOR; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BRAIN NATRIURETIC PEPTIDE; ENALAPRIL; HIGH DENSITY LIPOPROTEIN; LOSARTAN; LOW DENSITY LIPOPROTEIN; MATRIX METALLOPROTEINASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; RESVERATROL; RETINOL; SOMATOMEDIN C;

AGING; ALZHEIMER DISEASE; ANEMIA; ANGIOGENESIS; AORTA STENOSIS; AORTA VALVE DISEASE; ARTERIOLOSCLEROSIS; CAENORHABDITIS ELEGANS; CALCIFICATION; CANINE TOOTH; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CELL AGING; CONGESTIVE HEART FAILURE; DIABETES MELLITUS; DIASTOLIC DYSFUNCTION; DNA METHYLATION; DOPPLER ECHOCARDIOGRAPHY; DROSOPHILA MELANOGASTER; EXERCISE; GENE OVEREXPRESSION; HEART ARRHYTHMIA; HEART ATRIUM CONTRACTION; HEART ATRIUM FIBRILLATION; HEART EJECTION FRACTION; HEART INFARCTION; HEART LEFT VENTRICLE HYPERTROPHY; HEART MUSCLE FIBROSIS; HEART VENTRICLE HYPERTROPHY; HORMONAL REGULATION; HUMAN; HYPERLIPIDEMIA; HYPERTENSION; KIDNEY FAILURE; LIFESPAN; MEMBRANE DEPOLARIZATION; MITRAL VALVE REGURGITATION; MITRAL VALVE STENOSIS; MORBIDITY; MORTALITY; NATIONAL HEALTH ORGANIZATION; NEOPLASM; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; OSTEOPOROSIS; OXIDATIVE STRESS; PREVALENCE; PRIORITY JOURNAL; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; SACCHAROMYCES CEREVISIAE; STEM CELL; SYSTOLIC DYSFUNCTION; SYSTOLIC HEART MURMUR; TELOMERE;

ANIMALS; CARDIOVASCULAR DISEASES; HUMANS; MITOCHONDRIA; OXIDATIVE STRESS; SIGNAL TRANSDUCTION;

EID: 84860196585     PISSN: 15230864     EISSN: 15577716     Source Type: Journal    
DOI: 10.1089/ars.2011.4179     Document Type: Review

References (360)

1. Abadir PM, Foster DB, Crow M, Cooke CA, Rucker JJ, Jain A, Smith BJ, Burks TN, Cohn RD, Fedarko NS, Carey RM, O'Rourke B, and Walston JD. Identification and characterization of a functional mitochondrial angiotensin system. Proc Natl Acad Sci USA 108: 14849-14854, 2011.
2. Adlam VJ, Harrison JC, Porteous CM, James AM, Smith RA, Murphy MP, and Sammut IA. Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury. Faseb J 19: 1088-1095, 2005. (Pubitemid 40946434)
3. Ago T, Kuroda J, Pain J, Fu C, Li H, and Sadoshima J. Upregulation of Nox4 by hypertrophic stimuli promotes apoptosis and mitochondrial dysfunction in cardiac myocytes. Circ Res 106: 1253-1264, 2010.
4. Ahmed HM, Blaha MJ, Nasir K, Rivera JJ, and Blumenthal RS. Effects of physical activity on cardiovascular disease. Am J Cardiol, 109: 288-295, 2012.
5. Ahmet I, Tae HJ, de Cabo R, Lakatta EG, and Talan MI. Effects of calorie restriction on cardioprotection and cardiovascular health. J Mol Cell Cardiol 51: 263-271, 2011.
6. Akazawa H, Komazaki S, Shimomura H, Terasaki F, Zou Y, Takano H, Nagai T, and Komuro I. Diphtheria toxininduced autophagic cardiomyocyte death plays a pathogenic role in mouse model of heart failure. J Biol Chem 279: 41095-41103, 2004. (Pubitemid 39287711)
7. Akins CW, Daggett WM, Vlahakes GJ, Hilgenberg AD, Torchiana DF, Madsen JC, and Buckley MJ. Cardiac operations in patients 80 years old and older. Ann Thorac Surg 64: 606-614; discussion 614-615, 1997.
8. Alcendor RR, Gao S, Zhai P, Zablocki D, Holle E, Yu X, Tian B, Wagner T, Vatner SF, and Sadoshima J. Sirt1 regulates aging and resistance to oxidative stress in the heart. Circ Res 100: 1512-1521, 2007. (Pubitemid 46834764)
9. Anderson EJ, Lustig ME, Boyle KE, Woodlief TL, Kane DA, Lin CT, Price JW, 3rd, Kang L, Rabinovitch PS, Szeto HH, Houmard JA, Cortright RN, Wasserman DH, and Neufer PD. Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. J Clin Invest 119: 573-581, 2009.
10. Anderson RM, Bitterman KJ, Wood JG, Medvedik O, and Sinclair DA. Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae. Nature 423: 181-185, 2003. (Pubitemid 36569542)
11. Andersson DC, Fauconnier J, Yamada T, Lacampagne A, Zhang SJ, Katz A, and Westerblad H. Mitochondrial production of reactive oxygen species contributes to the betaadrenergic stimulation of mouse cardiomycytes. J Physiol 589: 1791-1801, 2011.
12. Antonenko YN, Avetisyan AV, Bakeeva LE, Chernyak BV, Chertkov VA, Domnina LV, Ivanova OY, Izyumov DS, Khailova LS, Klishin SS, Korshunova GA, Lyamzaev KG, Muntyan MS, Nepryakhina OK, Pashkovskaya AA, Pletjushkina OY, Pustovidko AV, Roginsky VA, Rokitskaya TI, Ruuge EK, Saprunova VB, Severina II, Simonyan RA, Skulachev IV, Skulachev MV, Sumbatyan NV, Sviryaeva IV, Tashlitsky VN, Vassiliev JM, Vyssokikh MY, Yaguzhinsky LS, Zamyatnin AA, Jr., and Skulachev VP. Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 1. Cationic plastoquinone derivatives: synthesis and in vitro studies. Biochemistry (Mosc) 73: 1273-1287, 2008.
13. Anversa P, Puntillo E, Nikitin P, Olivetti G, Capasso JM, and Sonnenblick EH. Effects of age on mechanical and structural properties of myocardium of Fischer 344 rats. Am J Physiol 256: H1440-H1449, 1989.
14. Anyukhovsky EP, Sosunov EA, Chandra P, Rosen TS, Boyden PA, Danilo P, Jr., and Rosen MR. Age-associated changes in electrophysiologic remodeling: a potential contributor to initiation of atrial fibrillation. Cardiovasc Res 66: 353-363, 2005. (Pubitemid 40471050)
15. Apfeld J and Kenyon C. Cell nonautonomy of C. elegans daf-2 function in the regulation of diapause and life span. Cell 95: 199-210, 1998. (Pubitemid 28473781)
16. Arbab-Zadeh A, Dijk E, Prasad A, Fu Q, Torres P, Zhang R, Thomas JD, Palmer D, and Levine BD. Effect of aging and physical activity on left ventricular compliance. Circulation 110: 1799-1805, 2004. (Pubitemid 39302657)
17. Aronow WS, Ahn C, Shirani J, and Kronzon I. Comparison of frequency of new coronary events in older subjects with and without valvular aortic sclerosis. Am J Cardiol 83: 599-600, A8, 1999. (Pubitemid 29097965)
18. Baccarelli A, Wright R, Bollati V, Litonjua A, Zanobetti A, Tarantini L, Sparrow D, Vokonas P, and Schwartz J. Ischemic heart disease and stroke in relation to blood DNA methylation. Epidemiology 21: 819-828, 2010.
19. Bakeeva LE, Barskov IV, Egorov MV, Isaev NK, Kapelko VI, Kazachenko AV, Kirpatovsky VI, Kozlovsky SV, Lakomkin VL, Levina SB, Pisarenko OI, Plotnikov EY, Saprunova VB, Serebryakova LI, Skulachev MV, Stelmashook EV, Studneva IM, Tskitishvili OV, Vasilyeva AK, Victorov IV, Zorov DB, and Skulachev VP. Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 2. Treatment of some ROS-and agerelated diseases (heart arrhythmia, heart infarctions, kidney ischemia, and stroke). Biochemistry (Mosc) 73: 1288-1299, 2008.
20. Barger JL, Kayo T, Vann JM, Arias EB, Wang J, Hacker TA, Wang Y, Raederstorff D, Morrow JD, Leeuwenburgh C, Allison DB, Saupe KW, Cartee GD, Weindruch R, and Prolla TA. A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS One 3: e2264, 2008.
21. Bass TM, Weinkove D, Houthoofd K, Gems D, and Partridge L. Effects of resveratrol on lifespan in Drosophila melanogaster and Caenorhabditis elegans. Mech Ageing Dev 128: 546-552, 2007. (Pubitemid 47498522)
22. Basso N, Cini R, Pietrelli A, Ferder L, Terragno NA, and Inserra F. Protective effect of long-term angiotensin II inhibition. Am J Physiol Heart Circ Physiol 293: H1351-H1358, 2007. (Pubitemid 47367173)
23. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, and Sinclair DA. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444: 337-342, 2006. (Pubitemid 44764104)
24. Baur JA and Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 5: 493-506, 2006. (Pubitemid 44136961)
25. Becker LB, vanden Hoek TL, Shao ZH, Li CQ, and Schumacker PT. Generation of superoxide in cardiomyocytes during ischemia before reperfusion. Am J Physiol 277: H2240-H2246, 1999. (Pubitemid 30048143)
26. Beer M, Seyfarth T, Sandstede J, Landschutz W, Lipke C, Kostler H, von Kienlin M, Harre K, Hahn D, and Neubauer S. Absolute concentrations of high-energy phosphate metabolites in normal, hypertrophied, and failing human myocardium measured noninvasively with (31)P-SLOOP magnetic resonance spectroscopy. J Am Coll Cardiol 40: 1267-1274, 2002.
27. Bellizzi D, Rose G, Cavalcante P, Covello G, Dato S, De Rango F, Greco V, Maggiolini M, Feraco E, Mari V, Franceschi C, Passarino G, and De Benedictis G. A novel VNTR enhancer within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ages. Genomics 85: 258-263, 2005. (Pubitemid 40164791)
28. Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, Kasahara H, Rota M, Musso E, Urbanek K, Leri A, Kajstura J, Nadal-Ginard B, and Anversa P. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114: 763-776, 2003. (Pubitemid 37186770)
29. Benigni A, Corna D, Zoja C, Sonzogni A, Latini R, Salio M, Conti S, Rottoli D, Longaretti L, Cassis P, Morigi M, Coffman TM, and Remuzzi G. Disruption of the Ang II type 1 receptor promotes longevity in mice. J Clin Invest 119: 524-530, 2009.
30. Beregi E and Regius O. Comparative morphological study of age related mitochondrial changes of the lymphocytes and skeletal muscle cells. Acta Morphol Hung 35: 219-224, 1987.
31. Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabe-Heider F, Walsh S, Zupicich J, Alkass K, Buchholz BA, Druid H, Jovinge S, and Frisen J. Evidence for cardiomyocyte renewal in humans. Science 324: 98-102, 2009.
32. Berk BC, Fujiwara K, and Lehoux S. ECM remodeling in hypertensive heart disease. J Clin Invest 117: 568-575, 2007. (Pubitemid 46348511)
33. Bers DM. Altered cardiac myocyte Ca regulation in heart failure. Physiology (Bethesda) 21: 380-387, 2006. (Pubitemid 44879246)
34. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, and Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA 297: 842-857, 2007. (Pubitemid 46333949)
35. Blasco MA, Lee HW, Hande MP, Samper E, Lansdorp PM, DePinho RA, and Greider CW. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 91: 25-34, 1997. (Pubitemid 27431310)
36. Boluyt MO, Converso K, Hwang HS, Mikkor A, and Russell MW. Echocardiographic assessment of age-associated changes in systolic and diastolic function of the female F344 rat heart. J Appl Physiol 96: 822-828, 2004. (Pubitemid 38140193)
37. Bordone L, Cohen D, Robinson A, Motta MC, van Veen E, Czopik A, Steele AD, Crowe H, Marmor S, Luo J, Gu W, and Guarente L. SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging Cell 6: 759-767, 2007. (Pubitemid 350131044)
38. Boyle AJ, Shih H, Hwang J, Ye J, Lee B, Zhang Y, Kwon D, Jun K, Zheng D, Sievers R, Angeli F, Yeghiazarians Y, and Lee R. Cardiomyopathy of aging in the mammalian heart is characterized by myocardial hypertrophy, fibrosis and a predisposition towards cardiomyocyte apoptosis and autophagy. Exp Gerontol 46: 549-559, 2011.
39. Braidy N, Guillemin GJ, Mansour H, Chan-Ling T, Poljak A, and Grant R. Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats. PLoS One 6: e19194, 2011.
40. Broglio F, Fubini A, Morello M, Arvat E, Aimaretti G, Gianotti L, Boghen MF, Deghenghi R, Mangiardi L, and Ghigo E. Activity of GH/IGF-I axis in patients with dilated cardiomyopathy. Clin Endocrinol (Oxf) 50: 417-430, 1999. (Pubitemid 29193224)
41. Brown VA, Patel KR, Viskaduraki M, Crowell JA, Perloff M, Booth TD, Vasilinin G, Sen A, Schinas AM, Piccirilli G, Brown K, Steward WP, Gescher AJ, and Brenner DE. Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis. Cancer Res 70: 9003-9011, 2010.
42. Brunk UT and Terman A. The mitochondrial-lysosomal axis theory of aging: accumulation of damaged mitochondria as a result of imperfect autophagocytosis. Eur J Biochem 269: 1996-2002, 2002. (Pubitemid 34437840)
43. Bursi F, Weston SA, Redfield MM, Jacobsen SJ, Pakhomov S, Nkomo VT, Meverden RA, and Roger VL. Systolic and diastolic heart failure in the community. Jama 296: 2209-2216, 2006. (Pubitemid 44708051)
44. Cadenas S, Aragones J, and Landazuri MO. Mitochondrial reprogramming through cardiac oxygen sensors in ischaemic heart disease. Cardiovasc Res 88: 219-228, 2010.
45. Cai Z, Zhong H, Bosch-Marce M, Fox-Talbot K, Wang L, Wei C, Trush MA, and Semenza GL. Complete loss of ischaemic preconditioning-induced cardioprotection in mice with partial deficiency of HIF-1 alpha. Cardiovasc Res 77: 463-470, 2008. (Pubitemid 351197653)
46. Camins A, Sureda FX, Junyent F, Verdaguer E, Folch J, Pelegri C, Vilaplana J, Beas-Zarate C, and Pallas M. Sirtuin activators: designing molecules to extend life span. Biochim Biophys Acta 1799: 740-749, 2010.
47. Chan DC. Mitochondria: dynamic organelles in disease, aging, and development. Cell 125: 1241-1252, 2006. (Pubitemid 43929096)
48. Chan NC, Salazar AM, Pham AH, Sweredoski MJ, Kolawa NJ, Graham RL, Hess S, and Chan DC. Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy. Hum Mol Genet 20: 1726-1737, 2011.
49. Chandel NS, Maltepe E, Goldwasser E, Mathieu CE, Simon MC, and Schumacker PT. Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc Natl Acad Sci USA 95: 11715-11720, 1998. (Pubitemid 28460480)
50. Chen H and Chan DC. Physiological functions of mitochondrial fusion. Ann N Y Acad Sci 1201: 21-25, 2010.
51. Chen H, Vermulst M, Wang YE, Chomyn A, Prolla TA, McCaffery JM, and Chan DC. Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations. Cell 141: 280-289, 2010.
52. Chimenti C, Kajstura J, Torella D, Urbanek K, Heleniak H, Colussi C, Di Meglio F, Nadal-Ginard B, Frustaci A, Leri A, Maseri A, and Anversa P. Senescence and death of primitive cells and myocytes lead to premature cardiac aging and heart failure. Circ Res 93: 604-613, 2003. (Pubitemid 37222156)
53. Chiribau CB, Cheng L, Cucoranu IC, Yu YS, Clempus RE, and Sorescu D. FOXO3A regulates peroxiredoxin III expression in human cardiac fibroblasts. J Biol Chem 283: 8211-8217, 2008.
54. Cho J, Won K, Wu D, Soong Y, Liu S, Szeto HH, and Hong MK. Potent mitochondria-targeted peptides reduce myocardial infarction in rats. Coron Artery Dis 18: 215-220, 2007. (Pubitemid 46608500)
55. Cho S, Szeto HH, Kim E, Kim H, Tolhurst AT, and Pinto JT. A novel cell-permeable antioxidant peptide, SS31, attenuates ischemic brain injury by down-regulating CD36. J Biol Chem 282: 4634-4642, 2007. (Pubitemid 47100960)
56. Chomyn A, Meola G, Bresolin N, Lai ST, Scarlato G, and Attardi G. In vitro genetic transfer of protein synthesis and respiration defects to mitochondrial DNA-less cells with myopathy-patient mitochondria. Mol Cell Biol 11: 2236-2244, 1991. (Pubitemid 21895596)
57. Chou TC, Yen MH, Li CY, and Ding YA. Alterations of nitric oxide synthase expression with aging and hypertension in rats. Hypertension 31: 643-648, 1998.
58. Chudyk A and Petrella RJ. Effects of exercise on cardiovascular risk factors in type 2 diabetes: a meta-analysis. Diabetes Care 34: 1228-1237, 2011.
59. Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, Allison DB, Cruzen C, Simmons HA, Kemnitz JW, and Weindruch R. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325: 201-204, 2009.
60. Colom B, Oliver J, Roca P, and Garcia-Palmer FJ. Caloric restriction and gender modulate cardiac muscle mitochondrial H2O2 production and oxidative damage. Cardiovasc Res 74: 456-465, 2007. (Pubitemid 46693701)
61. Corpas E, Harman SM, and Blackman MR. Human growth hormone and human aging. Endocr Rev 14: 20-39, 1993. (Pubitemid 23066530)
62. Corral-Debrinski M, Stepien G, Shoffner JM, Lott MT, Kanter K, and Wallace DC. Hypoxemia is associated with mitochondrial DNA damage and gene induction. Implications for cardiac disease. Jama 266: 1812-1816, 1991.
63. Correia LC, Lakatta EG, O'Connor FC, Becker LC, Clulow J, Townsend S, Gerstenblith G, and Fleg JL. Attenuated cardiovascular reserve during prolonged submaximal cycle exercise in healthy older subjects. J Am Coll Cardiol 40: 1290-1297, 2002.
64. Cruzen C and Colman RJ. Effects of caloric restriction on cardiovascular aging in non-human primates and humans. Clin Geriatr Med 25: 733-743, ix-x, 2009.
65. Curtis NJ, Ringo JM, and Dowse HB. Morphology of the pupal heart, adult heart, and associated tissues in the fruit fly, Drosophila melanogaster. J Morphol 240: 225-235, 1999. (Pubitemid 29273140)
66. Dai DF, Chen T, Szeto H, Nieves-Cintron M, Kutyavin V, Santana LF, and Rabinovitch PS. Mitochondrial targeted antioxidant peptide ameliorates hypertensive cardiomyopathy. J Am Coll Cardiol 58: 73-82, 2011.
67. Dai DF, Chen T, Wanagat J, Laflamme M, Marcinek DJ, Emond MJ, Ngo CP, and Prolla TA, Rabinovitch PS. Agedependent cardiomyopathy in mitochondrial mutator mice is attenuated by overexpression of catalase targeted to mitochondria. Aging Cell 9: 536-544, 2010.
68. Dai DF, Hwang JJ, Chen CL, Chiang FT, Lin JL, Hsu KL, Tseng CD, and Tseng YZ. Effect of physical activity on the prevalence of metabolic syndrome and left ventricular hypertrophy in apparently healthy adults. J Formos Med Assoc 109: 716-724, 2010.
69. Dai DF, Johnson SC, Villarin JJ, Chin MT, Nieves-Cintron M, Chen T, Marcinek DJ, Dorn GW, 2nd, Kang YJ, Prolla TA, Santana LF, and Rabinovitch PS. Mitochondrial oxidative stress mediates angiotensin II-induced cardiac hypertrophy and G{alpha}q overexpression-Induced heart failure. Circ Res 108: 837-846, 2011.
70. Dai DF and Rabinovitch PS. Cardiac aging in mice and humans: the role of mitochondrial oxidative stress. Trends Cardiovasc Med 19: 213-220, 2009.
71. Dai DF, Santana LF, Vermulst M, Tomazela DM, Emond MJ, MacCoss MJ, Gollahon K, Martin GM, Loeb LA, Ladiges WC, and Rabinovitch PS. Overexpression of catalase targeted to mitochondria attenuates murine cardiac aging. Circulation 119: 2789-2797, 2009.
72. De Meyer GR, De Keulenaer GW, and Martinet W. Role of autophagy in heart failure associated with aging. Heart Fail Rev 15: 423-430, 2010.
73. Di Lisa F and Bernardi P. Mitochondria and ischemia-reperfusion injury of the heart: fixing a hole. Cardiovasc Res 70: 191-199, 2006.
74. Di Lisa F and Bernardi P. A CaPful of mechanisms regulating the mitochondrial permeability transition. J Mol Cell Cardiol 46: 775-780, 2009.
75. Dickinson HO, Mason JM, Nicolson DJ, Campbell F, Beyer FR, Cook JV, Williams B, and Ford GA. Lifestyle interventions to reduce raised blood pressure: a systematic review of randomized controlled trials. J Hypertens 24: 215-233, 2006.
76. DiMauro S and Schon EA. Mitochondrial respiratory-chain diseases. N Engl J Med 348: 2656-2668, 2003. (Pubitemid 36741594)
77. Dorman JB, Albinder B, Shroyer T, and Kenyon C. The age-1 and daf-2 genes function in a common pathway to control the lifespan of Caenorhabditis elegans. Genetics 141: 1399-1406, 1995.
78. Doughan AK and Dikalov SI. Mitochondrial redox cycling of mitoquinone leads to superoxide production and cellular apoptosis. Antioxid Redox Signal 9: 1825-1836, 2007. (Pubitemid 47622346)
79. Doughan AK, Harrison DG, and Dikalov SI. Molecular mechanisms of angiotensin II-mediated mitochondrial dysfunction: linking mitochondrial oxidative damage and vascular endothelial dysfunction. Circ Res 102: 488-496, 2008. (Pubitemid 351651106)
80. Ducharme A, Frantz S, Aikawa M, Rabkin E, Lindsey M, Rohde LE, Schoen FJ, Kelly RA, Werb Z, Libby P, and Lee RT. Targeted deletion of matrix metalloproteinase-9 attenuates left ventricular enlargement and collagen accumulation after experimental myocardial infarction. J Clin Invest 106: 55-62, 2000. (Pubitemid 30437240)
81. Eckle T, Kohler D, Lehmann R, El Kasmi K, and Eltzschig HK. Hypoxia-inducible factor-1 is central to cardioprotection: a new paradigm for ischemic preconditioning. Circulation 118: 166-175, 2008.
82. Ellison KE and Gandhi G. Optimising the use of betaadrenoceptor antagonists in coronary artery disease. Drugs 65: 787-797, 2005. (Pubitemid 40593627)
83. Evans GB, Furneaux RH, Gainsford GJ, Hanson JC, Kicska GA, Sauve AA, Schramm VL, and Tyler PC. 8-Azaimmucillins as transition-state analogue inhibitors of purine nucleoside phosphorylase and nucleoside hydrolases. J Med Chem 46: 155-160, 2003. (Pubitemid 36043795)
84. Fagard RH. Effects of exercise, diet and their combination on blood pressure. J Hum Hypertens 19 Suppl 3: S20-S24, 2005. (Pubitemid 41823778)
85. Faggiano P, Antonini-Canterin F, Erlicher A, Romeo C, Cervesato E, Pavan D, Piazza R, Huang G, and Nicolosi GL. Progression of aortic valve sclerosis to aortic stenosis. Am J Cardiol 91: 99-101, 2003. (Pubitemid 36050784)
86. Finocchietto PV, Franco MC, Holod S, Gonzalez AS, Converso DP, Antico Arciuch VG, Serra MP, Poderoso JJ, and Carreras MC. Mitochondrial nitric oxide synthase: a masterpiece of metabolic adaptation, cell growth, transformation, and death. Exp Biol Med (Maywood) 234: 1020-1028, 2009.
87. Fleg JL, O'Connor F, Gerstenblith G, Becker LC, Clulow J, Schulman SP, and Lakatta EG. Impact of age on the cardiovascular response to dynamic upright exercise in healthy men and women. J Appl Physiol 78: 890-900, 1995.
88. Floreani M, Napoli E, Quintieri L, and Palatini P. Oral administration of trans-resveratrol to guinea pigs increases cardiac DT-diaphorase and catalase activities, and protects isolated atria from menadione toxicity. Life Sci 72: 2741-2750, 2003. (Pubitemid 36385079)
89. Flores-Mateo G, Carrillo-Santisteve P, Elosua R, Guallar E, Marrugat J, Bleys J, and Covas MI. Antioxidant enzyme activity and coronary heart disease: meta-analyses of observational studies. Am J Epidemiol 170: 135-147, 2009.
90. Foo RS, Mani K, and Kitsis RN. Death begets failure in the heart. J Clin Invest 115: 565-571, 2005. (Pubitemid 40322226)
91. Forman DE, Cittadini A, Azhar G, Douglas PS, and Wei JY. Cardiac morphology and function in senescent rats: gender-related differences. J Am Coll Cardiol 30: 1872-1877, 1997. (Pubitemid 27521276)
92. Fowler CG, Chiasson KB, Leslie TH, Thomas D, Beasley TM, Kemnitz JW, and Weindruch R. Auditory function in rhesus monkeys: effects of aging and caloric restriction in the Wisconsin monkeys five years later. Hear Res 261: 75-81, 2010.
93. Frankel EN, Waterhouse AL, and Kinsella JE. Inhibition of human LDL oxidation by resveratrol. Lancet 341: 1103-1104, 1993. (Pubitemid 23114451)
94. Freeman RV and Otto CM. Spectrum of calcific aortic valve disease: pathogenesis, disease progression, and treatment strategies. Circulation 111: 3316-3326, 2005. (Pubitemid 40875006)
95. Frishman WH. Fifty years of beta-adrenergic blockade: a golden era in clinical medicine and molecular pharmacology. Am J Med 121: 933-934, 2008.
96. Fujimoto N, Prasad A, Hastings JL, Arbab-Zadeh A, Bhella PS, Shibata S, Palmer D, and Levine BD. Cardiovascular effects of 1 year of progressive and vigorous exercise training in previously sedentary individuals older than 65 years of age. Circulation 122: 1797-1805, 2010.
97. Fulkerson PK, Beaver BM, Auseon JC, and Graber HL. Calcification of the mitral annulus: etiology, clinical associations, complications and therapy. Am J Med 66: 967-977, 1979. (Pubitemid 9198581)
98. Gane EJ, Weilert F, Orr DW, Keogh GF, Gibson M, Lockhart MM, Frampton CM, Taylor KM, Smith RA, and Murphy MP. The mitochondria-targeted anti-oxidant mitoquinone decreases liver damage in a phase II study of hepatitis C patients. Liver Int 30: 1019-1026, 2010.
99. Gao L, Wang W, Liu D, and Zucker IH. Exercise training normalizes sympathetic outflow by central antioxidant mechanisms in rabbits with pacing-induced chronic heart failure. Circulation 115: 3095-3102, 2007. (Pubitemid 46957475)
100. Gao XM, Wong G, Wang B, Kiriazis H, Moore XL, Su YD, Dart A, and Du XJ. Inhibition of mTOR reduces chronic pressure-overload cardiac hypertrophy and fibrosis. J Hypertens 24: 1663-1670, 2006. (Pubitemid 44162470)
101. Gardin JM and Lauer MS. Left ventricular hypertrophy: the next treatable, silent killer? Jama 292: 2396-2398, 2004. (Pubitemid 39491925)
102. Gates PE, Tanaka H, Graves J, and Seals DR. Left ventricular structure and diastolic function with human ageing. Relation to habitual exercise and arterial stiffness. Eur Heart J 24: 2213-2220, 2003. (Pubitemid 37522674)
103. Giannakou ME, Goss M, Junger MA, Hafen E, Leevers SJ, and Partridge L. Long-lived Drosophila with overexpressed dFOXO in adult fat body. Science 305: 361, 2004. (Pubitemid 38938145)
104. Gluckman PD, Hanson MA, Buklijas T, Low FM, and Beedle AS. Epigenetic mechanisms that underpin metabolic and cardiovascular diseases. Nat Rev Endocrinol 5: 401-408, 2009.
105. Goffart S, von Kleist-Retzow J-C, and Wiesner RJ. Regulation of mitochondrial proliferation in the heart: powerplant failure contributes to cardiac failure in hypertrophy. Cardiovascular Research 64: 198-207, 2004. (Pubitemid 39361680)
106. Gonzalez A, Rota M, Nurzynska D, Misao Y, Tillmanns J, Ojaimi C, Padin-Iruegas ME, Muller P, Esposito G, Bearzi C, Vitale S, Dawn B, Sanganalmath SK, Baker M, Hintze TH, Bolli R, Urbanek K, Hosoda T, Anversa P, Kajstura J, and Leri A. Activation of cardiac progenitor cells reverses the failing heart senescent phenotype and prolongs lifespan. Circ Res 102: 597-606, 2008. (Pubitemid 351416761)
107. Goswami SK and Das DK. Autophagy in the myocardium: dying for survival? Exp Clin Cardiol 11: 183-188, 2006. (Pubitemid 44548798)
108. Gottlieb RA and Carreira RS. Autophagy in health and disease. 5. Mitophagy as a way of life. Am J Physiol Cell Physiol 299: C203-C210, 2010.
109. Graham D, Huynh NN, Hamilton CA, Beattie E, Smith RA, Cocheme HM, Murphy MP, and Dominiczak AF. Mitochondria-targeted antioxidant MitoQ10 improves endothelial function and attenuates cardiac hypertrophy. Hypertension 54: 322-328, 2009.
110. Gravina S and Vijg J. Epigenetic factors in aging and longevity. Pflugers Arch 459: 247-258, 2010.
111. Groban L, Pailes NA, Bennett CD, Carter CS, Chappell MC, Kitzman DW, and Sonntag WE. Growth hormone replacement attenuates diastolic dysfunction and cardiac angiotensin II expression in senescent rats. J Gerontol A Biol Sci Med Sci 61: 28-35, 2006. (Pubitemid 43227799)
112. Guglielmini C. Cardiovascular diseases in the ageing dog: diagnostic and therapeutic problems. Vet Res Commun 27 Suppl 1: 555-560, 2003. (Pubitemid 37121394)
113. Guzy RD, Hoyos B, Robin E, Chen H, Liu L, Mansfield KD, Simon MC, Hammerling U, and Schumacker PT. Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing. Cell Metab 1: 401-408, 2005. (Pubitemid 43960623)
114. Hachamovitch R, Wicker P, Capasso JM, and Anversa P. Alterations of coronary blood flow and reserve with aging in Fischer 344 rats. Am J Physiol 256: H66-H73, 1989.
115. Hafner AV, Dai J, Gomes AP, Xiao CY, Palmeira CM, Rosenzweig A, and Sinclair DA. Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy. Aging (Albany NY) 2: 914-923, 2010.
116. Hamanaka RB and Chandel NS. Mitochondrial reactive oxygen species regulate hypoxic signaling. Curr Opin Cell Biol 21: 894-899, 2009.
117. Hamanaka RB and Chandel NS. Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes. Trends Biochem Sci 35: 505-513, 2010.
118. Hamlin RL. Animal models of ventricular arrhythmias. Pharmacol Ther 113: 276-295, 2007. (Pubitemid 46151721)
119. Hamlin RL and Smith CR. Anatomical and physiologic basis for interpretation of the electrocardiogram. Am J Vet Res 21: 701-708, 1960.
120. Hariharan N, Maejima Y, Nakae J, Paik J, Depinho RA, and Sadoshima J. Deacetylation of FoxO by Sirt1 Plays an Essential Role in Mediating Starvation-Induced Autophagy in Cardiac Myocytes. Circ Res 107: 1470-1482, 2010.
121. Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol 11: 298-300, 1956.
122. Harman D. The biologic clock: the mitochondria? J Am Geriatr Soc 20: 145-147, 1972.
123. Heineke J, Auger-Messier M, Xu J, Oka T, Sargent MA, York A, Klevitsky R, Vaikunth S, Duncan SA, Aronow BJ, Robbins J, Crombleholme TM, and Molkentin JD. Cardiomyocyte GATA4 functions as a stress-responsive regulator of angiogenesis in the murine heart. J Clin Invest 117: 3198-3210, 2007. (Pubitemid 350096978)
124. Hepple RT, Baker DJ, McConkey M, Murynka T, and Norris R. Caloric restriction protects mitochondrial function with aging in skeletal and cardiac muscles. Rejuvenation Res 9: 219-222, 2006. (Pubitemid 43856812)
125. Herbert KE, Mistry Y, Hastings R, Poolman T, Niklason L, and Williams B. Angiotensin II-mediated oxidative DNA damage accelerates cellular senescence in cultured human vascular smooth muscle cells via telomere-dependent and independent pathways. Circ Res 102: 201-208, 2008. (Pubitemid 351651124)
126. Hesselink RP, Schaart G, Wagenmakers AJ, Drost MR, and van der Vusse GJ. Age-related morphological changes in skeletal muscle cells of acid alpha-glucosidase knockout mice. Muscle Nerve 33: 505-513, 2006.
127. Hobai IA and O'Rourke B. Decreased sarcoplasmic reticulum calcium content is responsible for defective excitationcontraction coupling in canine heart failure. Circulation 103: 1577-1584, 2001. (Pubitemid 32226268)
128. Horton KL, Stewart KM, Fonseca SB, Guo Q, and Kelley SO. Mitochondria-penetrating peptides. Chem Biol 15: 375-382, 2008. (Pubitemid 351508434)
129. Hoshijima M, Ikeda Y, Iwanaga Y, Minamisawa S, Date MO, Gu Y, Iwatate M, Li M, Wang L, Wilson JM, Wang Y, Ross J, Jr., and Chien KR. Chronic suppression of heartfailure progression by a pseudophosphorylated mutant of phospholamban via in vivo cardiac rAAV gene delivery. Nat Med 8: 864-871, 2002.
130. Hosoi H, Dilling MB, Shikata T, Liu LN, Shu L, Ashmun RA, Germain GS, Abraham RT, and Houghton PJ. Rapamycin causes poorly reversible inhibition of mTOR and induces p53-independent apoptosis in human rhabdomyosarcoma cells. Cancer Res 59: 886-894, 1999. (Pubitemid 29086744)
131. Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, and Sinclair DA. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425: 191-196, 2003. (Pubitemid 37150899)
132. Huang TT, Carlson EJ, Gillespie AM, Shi Y, and Epstein CJ. Ubiquitous overexpression of CuZn superoxide dismutase does not extend life span in mice. J Gerontol A Biol Sci Med Sci 55: B5-B9, 2000. (Pubitemid 30140724)
133. Inserra F, Basso N, Ferder M, Userpater M, Stella I, Paglia N, Inserra P, Tenembaum D, and Ferder L. Changes seen in the aging kidney and the effect of blocking the reninangiotensin system. Ther Adv Cardiovasc Dis 3: 341-346, 2009.
134. Isoyama S and Nitta-Komatsubara Y. Acute and chronic adaptation to hemodynamic overload and ischemia in the aged heart. Heart Fail Rev 7: 63-69, 2002. (Pubitemid 34154900)
135. Izumiya Y, Shiojima I, Sato K, Sawyer DB, Colucci WS, and Walsh K. Vascular endothelial growth factor blockade promotes the transition from compensatory cardiac hypertrophy to failure in response to pressure overload. Hypertension 47: 887-893, 2006. (Pubitemid 44297560)
136. Jager S, Handschin C, St-Pierre J, and Spiegelman BM. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci USA 104: 12017-12022, 2007. (Pubitemid 47185622)
137. Jang YC, Perez VI, Song W, Lustgarten MS, Salmon AB, Mele J, Qi W, Liu Y, Liang H, Chaudhuri A, Ikeno Y, Epstein CJ, Van Remmen H, and Richardson A. Overexpression of Mn superoxide dismutase does not increase life span in mice. J Gerontol A Biol Sci Med Sci 64: 1114-1125, 2009.
138. Jebara VA, Dervanian P, Acar C, Grare P, Mihaileanu S, Chauvaud S, Fabiani JN, Deloche A, and Carpentier A. Mitral valve repair using Carpentier techniques in patients more than 70 years old. Early and late results. Circulation 86: II53-II59, 1992.
139. Jeon DS, Atar S, Brasch AV, Luo H, Mirocha J, Naqvi TZ, Kraus R, Berman DS, and Siegel RJ. Association of mitral annulus calcification, aortic valve sclerosis and aortic root calcification with abnormal myocardial perfusion single photon emission tomography in subjects age (Pubitemid 33116575)
140. Jian B, Narula N, Li QY, Mohler ER, 3rd, and Levy RJ. Progression of aortic valve stenosis: TGF-beta1 is present in calcified aortic valve cusps and promotes aortic valve interstitial cell calcification via apoptosis. Ann Thorac Surg 75: 457-465; discussion 465-6, 2003.
141. Jiang JC, Wawryn J, Shantha Kumara HM, and Jazwinski SM. Distinct roles of processes modulated by histone deacetylases Rpd3p, Hda1p, and Sir2p in life extension by caloric restriction in yeast. Exp Gerontol 37: 1023-1030, 2002.
142. Juhaszova M, Rabuel C, Zorov DB, Lakatta EG, and Sollott SJ. Protection in the aged heart: preventing the heart-break of old age? Cardiovasc Res 66: 233-244, 2005. (Pubitemid 40471038)
143. Kaeberlein M, Kirkland KT, Fields S, and Kennedy BK. Sir2-independent life span extension by calorie restriction in yeast. PLoS Biol 2: E296, 2004.
144. Kaeberlein M, McDonagh T, Heltweg B, Hixon J, Westman EA, Caldwell SD, Napper A, Curtis R, DiStefano PS, Fields S, Bedalov A, and Kennedy BK. Substrate-specific activation of sirtuins by resveratrol. J Biol Chem280: 17038-17045, 2005. (Pubitemid 41389166)
145. Karavidas A, Lazaros G, Tsiachris D, and Pyrgakis V. Aging and the cardiovascular system. Hellenic J Cardiol 51: 421-427, 2010.
146. Kastman EK, Willette AA, Coe CL, Bendlin BB, Kosmatka KJ, McLaren DG, Xu G, Canu E, Field AS, Alexander AL, Voytko ML, Beasley TM, Colman RJ, Weindruch RH, and Johnson SC. A calorie-restricted diet decreases brain iron accumulation and preserves motor performance in old rhesus monkeys. J Neurosci 30: 7940-7947, 2010.
147. Katzmarzyk PT, Leon AS, Wilmore JH, Skinner JS, Rao DC, Rankinen T, and Bouchard C. Targeting the metabolic syndrome with exercise: evidence from the HERITAGE Family Study. Med Sci Sports Exerc 35: 1703-1709, 2003. (Pubitemid 37221901)
148. Kelly G. A review of the sirtuin system, its clinical implications, and the potential role of dietary activators like resveratrol: part 1. Altern Med Rev 15: 245-263, 2010.
149. Kelly GS. A review of the sirtuin system, its clinical implications, and the potential role of dietary activators like resveratrol: part 2. Altern Med Rev 15: 313-328, 2010.
150. Kelso GF, Porteous CM, Coulter CV, Hughes G, Porteous WK, Ledgerwood EC, Smith RA, and Murphy MP. Selective targeting of a redox-active ubiquinone to mitochondria within cells: antioxidant and antiapoptotic properties. J Biol Chem 276: 4588-4596, 2001.
151. Kennedy BK, Steffen KK, and Kaeberlein M. Ruminations on dietary restriction and aging. Cell Mol Life Sci 64: 1323-1328, 2007. (Pubitemid 46889228)
152. Kenyon C, Chang J, Gensch E, Rudner A, and Tabtiang R. A C. elegans mutant that lives twice as long as wild type. Nature 366: 461-464, 1993. (Pubitemid 24013878)
153. Kimura S, Zhang GX, Nishiyama A, Shokoji T, Yao L, Fan YY, Rahman M, and Abe Y. Mitochondria-derived reactive oxygen species and vascular MAP kinases: comparison of angiotensin II and diazoxide. Hypertension 45: 438-444, 2005. (Pubitemid 40315815)
154. Koch LG, Kemi OJ, Qi N, Leng SX, Bijma P, Gilligan LJ, Wilkinson JE, Wisloff H, Hoydal MA, Rolim N, Abadir PM, van Grevenhof EM, Smith GL, Burant CF, Ellingsen O, Britton SL, and Wisloff U. Intrinsic aerobic capacity sets a divide for aging and longevity. Circ Res 109: 1162-1172, 2011.
155. Kodama S, Tanaka S, Saito K, Shu M, Sone Y, Onitake F, Suzuki E, Shimano H, Yamamoto S, Kondo K, Ohashi Y, Yamada N, and Sone H. Effect of aerobic exercise training on serum levels of high-density lipoprotein cholesterol: a meta-analysis. Arch Intern Med 167: 999-1008, 2007. (Pubitemid 46835787)
156. Koh GY, Soonpaa MH, Klug MG, Pride HP, Cooper BJ, Zipes DP, and Field LJ. Stable fetal cardiomyocyte grafts in the hearts of dystrophic mice and dogs. J Clin Invest 96: 2034-2042, 1995.
157. Kops GJ, Dansen TB, Polderman PE, Saarloos I, Wirtz KW, Coffer PJ, Huang TT, Bos JL, Medema RH, and Burgering BM. Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress. Nature 419: 316-321, 2002.
158. Korzick DH, Holiman DA, Boluyt MO, Laughlin MH, and Lakatta EG. Diminished alpha1-adrenergic-mediated contraction and translocation of PKC in senescent rat heart. Am J Physiol Heart Circ Physiol 281: H581-H589, 2001.
159. Kostin S, Pool L, Elsasser A, Hein S, Drexler HC, Arnon E, Hayakawa Y, Zimmermann R, Bauer E, Klovekorn WP, and Schaper J. Myocytes die by multiple mechanisms in failing human hearts. Circ Res 92: 715-724, 2003. (Pubitemid 36457635)
160. Kosugi R, Shioi T, Watanabe-Maeda K, Yoshida Y, Takahashi K, Machida Y, and Izumi T. Angiotensin II receptor antagonist attenuates expression of aging markers in diabetic mouse heart. Circ J 70: 482-488, 2006.
161. Kowald A, Kirkwood TB. Evolution of the mitochondrial fusion-fission cycle and its role in aging. Proc Natl Acad Sci USA 108: 10237-42, 2011.
162. Kraus WE, Houmard JA, Duscha BD, Knetzger KJ, Wharton MB, McCartney JS, Bales CW, Henes S, Samsa GP, Otvos JD, Kulkarni KR, and Slentz CA. Effects of the amount and intensity of exercise on plasma lipoproteins. N Engl J Med 347: 1483-1492, 2002. (Pubitemid 35257587)
163. Krause K, Schneider C, Kuck KH, and Jaquet K. Stem cell therapy in cardiovascular disorders. Cardiovasc Ther 28: e101-e110, 2010.
164. Kris-Etherton PM, Lichtenstein AH, Howard BV, Steinberg D, and Witztum JL. Antioxidant vitamin supplements and cardiovascular disease. Circulation 110: 637-641, 2004. (Pubitemid 39031177)
165. Kroemer G and Levine B. Autophagic cell death: the story of a misnomer. Nat Rev Mol Cell Biol 9: 1004-1010, 2008.
166. Kujoth GC, Hiona A, Pugh TD, Someya S, Panzer K, Wohlgemuth SE, Hofer T, Seo AY, Sullivan R, Jobling WA, Morrow JD, Van Remmen H, Sedivy JM, Yamasoba T, Tanokura M, Weindruch R, Leeuwenburgh C, and Prolla TA. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 309: 481-484, 2005. (Pubitemid 40994689)
167. Kumaran S, Savitha S, Anusuya Devi M, and Panneerselvam C. L-carnitine and DL-alpha-lipoic acid reverse the age-related deficit in glutathione redox state in skeletal muscle and heart tissues. Mech Ageing Dev 125: 507-512, 2004. (Pubitemid 38916609)
168. Kuroda J, Ago T, Matsushima S, Zhai P, Schneider MD, and Sadoshima J. NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart. Proc Natl Acad Sci USA 107: 15565-15570, 2010.
169. Kurosu H, Yamamoto M, Clark JD, Pastor JV, Nandi A, Gurnani P, McGuinness OP, Chikuda H, Yamaguchi M, Kawaguchi H, Shimomura I, Takayama Y, Herz J, Kahn CR, Rosenblatt KP, and Kuro-o M. Suppression of aging in mice by the hormone Klotho. Science 309: 1829-1833, 2005. (Pubitemid 41325087)
170. Kusama S, Ueda R, Suda T, Nishihara S, and Matsuura ET. Involvement of Drosophila Sir2-like genes in the regulation of life span. Genes Genet Syst 81: 341-348, 2006. (Pubitemid 44912785)
171. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, and Auwerx J. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127: 1109-1122, 2006. (Pubitemid 44894520)
172. Lakatta EG. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part III: cellular and molecular clues to heart and arterial aging. Circulation 107: 490-497, 2003. (Pubitemid 36158054)
173. Lakatta EG and Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part I: aging arteries: a "set up" for vascular disease. Circulation 107: 139-146, 2003. (Pubitemid 36070946)
174. Lakatta EG and Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part II: the aging heart in health: links to heart disease. Circulation 107: 346-354, 2003. (Pubitemid 36135235)
175. Lane MA, Ingram DK, and Roth GS. Calorie restriction in nonhuman primates: effects on diabetes and cardiovascular disease risk. Toxicol Sci 52: 41-48, 1999. (Pubitemid 30017574)
176. Lane MA, Mattison J, Ingram DK, and Roth GS. Caloric restriction and aging in primates: relevance to humans and possible CR mimetics. Microsc Res Tech 59: 335-338, 2002. (Pubitemid 35332955)
177. Lanza IR, Short DK, Short KR, Raghavakaimal S, Basu R, Joyner MJ, McConnell JP, and Nair KS. Endurance exercise as a countermeasure for aging. Diabetes 57: 2933-2942, 2008.
178. Lee RT. Matrix metalloproteinase inhibition and the prevention of heart failure. Trends Cardiovasc Med 11: 202-205, 2001. (Pubitemid 32946868)
179. Lee SJ, Hwang AB, and Kenyon C. Inhibition of respiration extends C. elegans life span via reactive oxygen species that increase HIF-1 activity. Curr Biol 20: 2131-2136, 2010.
180. Lennox SD, Mulkerrin E, Penney M, and Woodhouse K. Plasma atrial natriuretic polypeptide in the elderly: age or hypertension? Arch Gerontol Geriatr 19: 1-5, 1994. (Pubitemid 24296291)
181. Leon AS, Rice T, Mandel S, Despres JP, Bergeron J, Gagnon J, Rao DC, Skinner JS, Wilmore JH, and Bouchard C. Blood lipid response to 20 weeks of supervised exercise in a large biracial population: the HERITAGE Family Study. Metabolism 49: 513-520, 2000. (Pubitemid 30196580)
182. Leosco D, Rengo G, Iaccarino G, Filippelli A, Lymperopoulos A, Zincarelli C, Fortunato F, Golino L, Marchese M, Esposito G, Rapacciuolo A, Rinaldi B, Ferrara N, Koch WJ, and Rengo F. Exercise training and beta-blocker treatment ameliorate age-dependent impairment of beta-adrenergic receptor signaling and enhance cardiac responsiveness to adrenergic stimulation. Am J Physiol Heart Circ Physiol 293: H1596-H1603, 2007. (Pubitemid 47367205)
183. Levine B and Yuan J. Autophagy in cell death: an innocent convict? J Clin Invest 115: 2679-2688, 2005. (Pubitemid 41434392)
184. Li HF, Chen SA, and Wu SN. Evidence for the stimulatory effect of resveratrol on Ca(2 + )-activated K+ current in vascular endothelial cells. Cardiovasc Res 45: 1035-1045, 2000.
185. Li HH, Kedar V, Zhang C, McDonough H, Arya R, Wang DZ, and Patterson C. Atrogin-1/muscle atrophy F-box inhibits calcineurin-dependent cardiac hypertrophy by participating in an SCF ubiquitin ligase complex. J Clin Invest 114: 1058-1071, 2004. (Pubitemid 39578695)
186. Li HH, Willis MS, Lockyer P, Miller N, McDonough H, Glass DJ, and Patterson C. Atrogin-1 inhibits Akt-dependent cardiac hypertrophy in mice via ubiquitin-dependent coactivation of Forkhead proteins. J Clin Invest 117: 3211-3223, 2007. (Pubitemid 350096979)
187. Li L, Pan R, Li R, Niemann B, Aurich AC, Chen Y, and Rohrbach S. Mitochondrial biogenesis and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) deacetylation by physical activity: intact adipocytokine signaling is required. Diabetes 60: 157-167, 2011.
188. Li Q, Ceylan-Isik AF, Li J, and Ren J. Deficiency of insulinlike growth factor 1 reduces sensitivity to aging-associated cardiomyocyte dysfunction. Rejuvenation Res 11: 725-733, 2008.
189. Liang H, Masoro EJ, Nelson JF, Strong R, McMahan CA, and Richardson A. Genetic mouse models of extended lifespan. Exp Gerontol 38: 1353-1364, 2003. (Pubitemid 38041223)
190. Lifton RP, Gharavi AG, and Geller DS. Molecular mechanisms of human hypertension. Cell 104: 545-556, 2001. (Pubitemid 32201949)
191. Lin J, Wu H, Tarr PT, Zhang CY, Wu Z, Boss O, Michael LF, Puigserver P, Isotani E, Olson EN, Lowell BB, Bassel-Duby R, and Spiegelman BM. Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature 418: 797-801, 2002.
192. Lin K, Dorman JB, Rodan A, and Kenyon C. daf-16: an HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science 278: 1319-1322, 1997. (Pubitemid 27495748)
193. Lin SJ, Kaeberlein M, Andalis AA, Sturtz LA, Defossez PA, Culotta VC, Fink GR, and Guarente L. Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration. Nature 418: 344-348, 2002. (Pubitemid 34790687)
194. Lindsey ML, Escobar GP, Dobrucki LW, Goshorn DK, Bouges S, Mingoia JT, McClister DM, Jr., Su H, Gannon J, MacGillivray C, Lee RT, Sinusas AJ, and Spinale FG. Matrix metalloproteinase-9 gene deletion facilitates angiogenesis after myocardial infarction. Am J Physiol Heart Circ Physiol 290: H232-H239, 2006.
195. Lindsey ML, Gannon J, Aikawa M, Schoen FJ, Rabkin E, Lopresti-Morrow L, Crawford J, Black S, Libby P, Mitchell PG, and Lee RT. Selective matrix metalloproteinase inhibition reduces left ventricular remodeling but does not inhibit angiogenesis after myocardial infarction. Circulation 105: 753-758, 2002. (Pubitemid 34157381)
196. Lindsey ML, Goshorn DK, Squires CE, Escobar GP, Hendrick JW, Mingoia JT, Sweterlitsch SE, and Spinale FG. Age-dependent changes in myocardial matrix metalloproteinase/tissue inhibitor of metalloproteinase profiles and fibroblast function. Cardiovasc Res 66: 410-419, 2005. (Pubitemid 40471056)
197. Luong N, Davies CR, Wessells RJ, Graham SM, King MT, Veech R, Bodmer R, and Oldham SM. Activated FOXOmediated insulin resistance is blocked by reduction of TOR activity. Cell Metab 4: 133-142, 2006. (Pubitemid 44138719)
198. Magwere T, West M, Riyahi K, Murphy MP, Smith RA, and Partridge L. The effects of exogenous antioxidants on lifespan and oxidative stress resistance in Drosophila melanogaster. Mech Ageing Dev 127: 356-370, 2006. (Pubitemid 43290539)
199. Mammucari C and Rizzuto R. Signaling pathways in mitochondrial dysfunction and aging. Mech Ageing Dev 131: 536-543, 2010.
200. Marin-Garcia J, Goldenthal MJ, and Moe GW. Abnormal cardiac and skeletal muscle mitochondrial function in pacing-induced cardiac failure. Cardiovasc Res 52: 103-110, 2001. (Pubitemid 32835243)
201. Mattison JA, Lane MA, Roth GS, and Ingram DK. Calorie restriction in rhesus monkeys. Exp Gerontol 38: 35-46, 2003. (Pubitemid 36110497)
202. Mattson MP and Wan R. Beneficial effects of intermittent fasting and caloric restriction on the cardiovascular and cerebrovascular systems. J Nutr Biochem 16: 129-137, 2005. (Pubitemid 40312164)
203. McKiernan SH, Colman RJ, Lopez M, Beasley TM, Aiken JM, Anderson RM, and Weindruch R. Caloric restriction delays aging-induced cellular phenotypes in rhesus monkey skeletal muscle. Exp Gerontol 46: 23-29, 2011.
204. McMullen JR, Sherwood MC, Tarnavski O, Zhang L, Dorfman AL, Shioi T, and Izumo S. Inhibition of mTOR signaling with rapamycin regresses established cardiac hypertrophy induced by pressure overload. Circulation 109: 3050-3055, 2004. (Pubitemid 38808328)
205. McMullen JR, Shioi T, Zhang L, Tarnavski O, Sherwood MC, Dorfman AL, Longnus S, Pende M, Martin KA, Blenis J, Thomas G, and Izumo S. Deletion of ribosomal S6 kinases does not attenuate pathological, physiological, or insulinlike growth factor 1 receptor-phosphoinositide 3-kinaseinduced cardiac hypertrophy. Mol Cell Biol 24: 6231-6240, 2004. (Pubitemid 38891125)
206. Meyer TE, Kovacs SJ, Ehsani AA, Klein S, Holloszy JO, and Fontana L. Long-term caloric restriction ameliorates the decline in diastolic function in humans. J Am Coll Cardiol 47: 398-402, 2006. (Pubitemid 43063261)
207. Miller RA, Harrison DE, Astle CM, Baur JA, Boyd AR, de Cabo R, Fernandez E, Flurkey K, Javors MA, Nelson JF, Orihuela CJ, Pletcher S, Sharp ZD, Sinclair D, Starnes JW, Wilkinson JE, Nadon NL, and Strong R. Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. J Gerontol A Biol Sci Med Sci 66: 191-201, 2011.
208. Minamisawa S, Hoshijima M, Chu G, Ward CA, Frank K, Gu Y, Martone ME, Wang Y, Ross J, Jr., Kranias EG, Giles WR, and Chien KR. Chronic phospholamban-sarcoplasmic reticulum calcium ATPase interaction is the critical calcium cycling defect in dilated cardiomyopathy. Cell 99: 313-322, 1999. (Pubitemid 29519910)
209. Minamiyama Y, Bito Y, Takemura S, Takahashi Y, Kodai S, Mizuguchi S, Nishikawa Y, Suehiro S, and Okada S. Calorie restriction improves cardiovascular risk factors via reduction of mitochondrial reactive oxygen species in type II diabetic rats. J Pharmacol Exp Ther 320: 535-543, 2007. (Pubitemid 46147931)
210. Miyamoto MI, del Monte F, Schmidt U, DiSalvo TS, Kang ZB, Matsui T, Guerrero JL, Gwathmey JK, Rosenzweig A, and Hajjar RJ. Adenoviral gene transfer of SERCA2a improves left-ventricular function in aortic-banded rats in transition to heart failure. Proc Natl Acad Sci USA 97: 793-798, 2000. (Pubitemid 30070389)
211. Mizutani K, Ikeda K, Kawai Y, and Yamori Y. Protective effect of resveratrol on oxidative damage in male and female stroke-prone spontaneously hypertensive rats. Clin Exp Pharmacol Physiol 28: 55-59, 2001. (Pubitemid 32039558)
212. Mockett RJ, Bayne AC, Kwong LK, Orr WC, and Sohal RS. Ectopic expression of catalase in Drosophila mitochondria increases stress resistance but not longevity. Free Radic Biol Med 34: 207-217, 2003. (Pubitemid 36084324)
213. Mockett RJ, Sohal RS, and Orr WC. Overexpression of glutathione reductase extends survival in transgenic Drosophila melanogaster under hyperoxia but not normoxia. FASEB J 13: 1733-1742, 1999. (Pubitemid 29473335)
214. Mollnau H, Wendt M, Szocs K, Lassegue B, Schulz E, Oelze M, Li H, Bodenschatz M, August M, Kleschyov AL, Tsilimingas N, Walter U, Forstermann U, Meinertz T, Griendling K, and Munzel T. Effects of angiotensin II infusion on the expression and function of NAD(P)H oxidase and components of nitric oxide/cGMP signaling. Circ Res 90: E58-E65, 2002.
215. Mora S, Lee IM, Buring JE, and Ridker PM. Association of physical activity and body mass index with novel and traditional cardiovascular biomarkers in women. JAMA 295: 1412-1419, 2006.
216. Murphy MP and Smith RA. Targeting antioxidants to mitochondria by conjugation to lipophilic cations. Annu Rev Pharmacol Toxicol 47: 629-656, 2007.
217. Murray AJ, Anderson RE, Watson GC, Radda GK, and Clarke K. Uncoupling proteins in human heart. Lancet 364: 1786-1788, 2004. (Pubitemid 39488064)
218. Muscari C, Caldarera CM, and Guarnieri C. Age-dependent production of mitochondrial hydrogen peroxide, lipid peroxides and fluorescent pigments in the rat heart. Basic Res Cardiol 85: 172-178, 1990. (Pubitemid 20150093)
219. Muster AJ, Kim H, Kane B, and McPherson DD. Ten-year echo/doppler determination of the benefits of aerobic exercise after the age of 65 years. Echocardiography 27: 5-10, 2010.
220. Muthusamy VR, Kannan S, Sadhaasivam K, Gounder SS, Davidson CJ, Boeheme C, Hoidal JR, Wang L, and Soorappan RN. Acute exercise stress activates Nrf2/ARE signaling and promotes antioxidant mechanisms in the myocardium. Free Radic Biol Med, 52: 366-376, 2012.
221. Nadal-Ginard B, Kajstura J, Leri A, and Anversa P. Myocyte death, growth, and regeneration in cardiac hypertrophy and failure. Circ Res 92: 139-150, 2003. (Pubitemid 36254270)
222. Nakada K, Inoue K, Ono T, Isobe K, Ogura A, Goto YI, Nonaka I, and Hayashi JI. Inter-mitochondrial complementation: mitochondria-specific system preventing mice from expression of disease phenotypes by mutant mtDNA. Nat Med 7: 934-940, 2001. (Pubitemid 32756431)
223. Nakada K, Sato A, and Hayashi J. Mitochondrial functional complementation in mitochondrial DNA-based diseases. Int J Biochem Cell Biol 41: 1907-1913, 2009.
224. Nakae I, Mitsunami K, Omura T, Yabe T, Tsutamoto T, Matsuo S, Takahashi M, Morikawa S, Inubushi T, Nakamura Y, Kinoshita M, and Horie M. Proton magnetic resonance spectroscopy can detect creatine depletion associated with the progression of heart failure in cardiomyopathy. J Am Coll Cardiol 42: 1587-1593, 2003. (Pubitemid 37378437)
225. Nakai A, Yamaguchi O, Takeda T, Higuchi Y, Hikoso S, Taniike M, Omiya S, Mizote I, Matsumura Y, Asahi M, Nishida K, Hori M, Mizushima N, and Otsu K. The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress. Nat Med 13: 619-624, 2007. (Pubitemid 46828485)
226. Nakayama H, Chen X, Baines CP, Klevitsky R, Zhang X, Zhang H, Jaleel N, Chua BH, Hewett TE, Robbins J, Houser SR, and Molkentin JD. Ca2 +-and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure. J Clin Invest 117: 2431-2444, 2007. (Pubitemid 47494345)
227. Nassimiha D, Aronow WS, Ahn C, and Goldman ME. Association of coronary risk factors with progression of valvular aortic stenosis in older persons. Am J Cardiol 87: 1313-1314, 2001. (Pubitemid 32493881)
228. Navarro A and Boveris A. The mitochondrial energy transduction system and the aging process. Am J Physiol Cell Physiol 292: C670-C686, 2007.
229. Neubauer S, Horn M, Cramer M, Harre K, Newell JB, Peters W, Pabst T, Ertl G, Hahn D, Ingwall JS, and Kochsiek K. Myocardial phosphocreatine-to-ATP ratio is a predictor of mortality in patients with dilated cardiomyopathy. Circulation 96: 2190-2196, 1997. (Pubitemid 27425822)
230. Niemann B, Chen Y, Issa H, Silber RE, and Rohrbach S. Caloric restriction delays cardiac ageing in rats: role of mitochondria. Cardiovasc Res 88: 267-276, 2010.
231. Niemann B, Chen Y, Teschner M, Li L, Silber RE, and Rohrbach S. Obesity induces signs of premature cardiac aging in younger patients: the role of mitochondria. J Am Coll Cardiol 57: 577-585, 2011.
232. Nitta Y, Abe K, Aoki M, Ohno I, and Isoyama S. Diminished heat shock protein 70 mRNA induction in aged rat hearts after ischemia. Am J Physiol 267: H1795-H1803, 1994. (Pubitemid 24363726)
233. O'Malley Y, Fink BD, Ross NC, Prisinzano TE, and Sivitz WI. Reactive oxygen and targeted antioxidant administration in endothelial cell mitochondria. J Biol Chem 281: 39766-39775, 2006. (Pubitemid 46041780)
234. O'Rourke B, Kass DA, Tomaselli GF, Kaab S, Tunin R, and Marban E. Mechanisms of altered excitation-contraction coupling in canine tachycardia-induced heart failure, I: experimental studies. Circ Res 84: 562-570, 1999. (Pubitemid 29138593)
235. O'Rourke MF and Hashimoto J. Mechanical factors in arterial aging: a clinical perspective. J Am Coll Cardiol 50: 1-13, 2007. (Pubitemid 46963521)
236. Ocorr K, Akasaka T, and Bodmer R. Age-related cardiac disease model of Drosophila. Mech Ageing Dev 128: 112-116, 2007. (Pubitemid 46075231)
237. Ocorr K, Reeves NL, Wessells RJ, Fink M, Chen HS, Akasaka T, Yasuda S, Metzger JM, Giles W, Posakony JW, and Bodmer R. KCNQ potassium channel mutations cause cardiac arrhythmias in Drosophila that mimic the effects of aging. Proc Natl Acad Sci USA 104: 3943-3948, 2007. (Pubitemid 47181558)
238. Oh H, Taffet GE, Youker KA, Entman ML, Overbeek PA, Michael LH, and Schneider MD. Telomerase reverse transcriptase promotes cardiac muscle cell proliferation, hypertrophy, and survival. Proc Natl Acad Sci USA 98: 10308-10313, 2001. (Pubitemid 32803016)
239. Oka T and Komuro I. Molecular mechanisms underlying the transition of cardiac hypertrophy to heart failure. Circulation J Supp A: A13-A16, 2008.
240. Okumura S, Takagi G, Kawabe J, Yang G, Lee MC, Hong C, Liu J, Vatner DE, Sadoshima J, Vatner SF, and Ishikawa Y. Disruption of type 5 adenylyl cyclase gene preserves cardiac function against pressure overload. Proc Natl Acad Sci USA 100: 9986-9990, 2003. (Pubitemid 37087055)
241. Okumura S, Vatner DE, Kurotani R, Bai Y, Gao S, Yuan Z, Iwatsubo K, Ulucan C, Kawabe J, Ghosh K, Vatner SF, and Ishikawa Y. Disruption of type 5 adenylyl cyclase enhances desensitization of cyclic adenosine monophosphate signal and increases Akt signal with chronic catecholamine stress. Circulation 116: 1776-1783, 2007. (Pubitemid 350287102)
242. Olsen MH, Wachtell K, Bella JN, Gerdts E, Palmieri V, Nieminen MS, Smith G, Ibsen H, and Devereux RB. Aortic valve sclerosis relates to cardiovascular events in patients with hypertension (a LIFE substudy). Am J Cardiol 95: 132-136, 2005. (Pubitemid 40051130)
243. Orallo F, Alvarez E, Camina M, Leiro JM, Gomez E, and Fernandez P. The possible implication of trans-Resveratrol in the cardioprotective effects of long-term moderate wine consumption. Mol Pharmacol 61: 294-302, 2002. (Pubitemid 34112803)
244. Oshiro N, Yoshino K, Hidayat S, Tokunaga C, Hara K, Eguchi S, Avruch J, and Yonezawa K. Dissociation of raptor from mTOR is a mechanism of rapamycin-induced inhibition of mTOR function. Genes Cells 9: 359-366, 2004. (Pubitemid 38514871)
245. Otto CM. Why is aortic sclerosis associated with adverse clinical outcomes? J Am Coll Cardiol 43: 176-178, 2004. (Pubitemid 38201140)
246. Otto CM, Lind BK, Kitzman DW, Gersh BJ, and Siscovick DS. Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly. N Engl J Med 341: 142-147, 1999. (Pubitemid 29325741)
247. Paddenberg R, Stieger P, von Lilien AL, Faulhammer P, Goldenberg A, Tillmanns HH, Kummer W, and Braun-Dullaeus RC. Rapamycin attenuates hypoxia-induced pulmonary vascular remodeling and right ventricular hypertrophy in mice. Respir Res 8: 15, 2007.
248. Palacios OM, Carmona JJ, Michan S, Chen KY, Manabe Y, Ward JL, 3rd, Goodyear LJ, and Tong Q. Diet and exercise signals regulate SIRT3 and activate AMPK and PGC-1alpha in skeletal muscle. Aging (Albany NY) 1: 771-783, 2009.
249. Panagiotakos DB, Pitsavos C, Chrysohoou C, Skoumas J, Tousoulis D, Toutouza M, Toutouzas P, and Stefanadis C. Impact of lifestyle habits on the prevalence of the metabolic syndrome among Greek adults from the ATTICA study. Am Heart J 147: 106-112, 2004. (Pubitemid 38037405)
250. Parkes TL, Elia AJ, Dickinson D, Hilliker AJ, Phillips JP, and Boulianne GL. Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons. Nat Genet 19: 171-174, 1998. (Pubitemid 28248800)
251. Patel KR, Brown VA, Jones DJ, Britton RG, Hemingway D, Miller AS, West KP, Booth TD, Perloff M, Crowell JA, Brenner DE, Steward WP, Gescher AJ, and Brown K. Clinical pharmacology of resveratrol and its metabolites in colorectal cancer patients. Cancer Res 70: 7392-7399, 2010.
252. Patel KR, Scott E, Brown VA, Gescher AJ, Steward WP, and Brown K. Clinical trials of resveratrol. Ann N Y Acad Sci 1215: 161-169, 2011.
253. Perez VI, Van Remmen H, Bokov A, Epstein CJ, Vijg J, and Richardson A. The overexpression of major antioxidant enzymes does not extend the lifespan of mice. Aging Cell 8: 73-75, 2009.
254. Petri S, Kiaei M, Damiano M, Hiller A, Wille E, Manfredi G, Calingasan NY, Szeto HH, and Beal MF. Cell-permeable peptide antioxidants as a novel therapeutic approach in a mouse model of amyotrophic lateral sclerosis. J Neurochem 98: 1141-1148, 2006. (Pubitemid 44127789)
255. Pillai VB, Sundaresan NR, Kim G, Gupta M, Rajamohan SB, Pillai JB, Samant S, Ravindra PV, Isbatan A, and Gupta MP. Exogenous NAD blocks cardiac hypertrophic response via activation of the SIRT3-LKB1-AMP-activated kinase pathway. J Biol Chem 285: 3133-3144, 2010.
256. Piot C, Croisille P, Staat P, Thibault H, Rioufol G, Mewton N, Elbelghiti R, Cung TT, Bonnefoy E, Angoulvant D, Macia C, Raczka F, Sportouch C, Gahide G, Finet G, Andre-Fouet X, Revel D, Kirkorian G, Monassier JP, Derumeaux G, and Ovize M. Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N Engl J Med 359: 473-481, 2008.
257. Plecita-Hlavata L, Jezek J, and Jezek P. Pro-oxidant mitochondrial matrix-targeted ubiquinone MitoQ10 acts as anti-oxidant at retarded electron transport or proton pumping within Complex I. Int J Biochem Cell Biol 41: 1697-1707, 2009.
258. Poderoso JJ, Carreras MC, Lisdero C, Riobo N, Schopfer F, and Boveris A. Nitric oxide inhibits electron transfer and increases superoxide radical production in rat heart mitochondria and submitochondrial particles. Arch Biochem Biophys 328: 85-92, 1996. (Pubitemid 26108173)
259. Polak JF, Pencina MJ, Pencina KM, O'Donnell CJ, Wolf PA, and D'Agostino RB, Sr. Carotid-wall intima-media thickness and cardiovascular events. N Engl J Med 365: 213-221, 2011.
260. Puigserver P, Rhee J, Donovan J, Walkey CJ, Yoon JC, Oriente F, Kitamura Y, Altomonte J, Dong H, Accili D, and Spiegelman BM. Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction. Nature 423: 550-555, 2003. (Pubitemid 36648580)
261. Rabinowitz M and Zak R. Mitochondria and cardiac hypertrophy. Circ Res 36: 367-376, 1975.
262. Radi R, Cassina A, Hodara R, Quijano C, and Castro L. Peroxynitrite reactions and formation in mitochondria. Free Radic Biol Med 33: 1451-1464, 2002. (Pubitemid 35351588)
263. Ravikumar B, Vacher C, Berger Z, Davies JE, Luo S,Oroz LG, Scaravilli F, EastonDF,Duden R, O'Kane CJ, and Rubinsztein DC. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet 36: 585-595, 2004. (Pubitemid 38715985)
264. Rebrin I, Kamzalov S, and Sohal RS. Effects of age and caloric restriction on glutathione redox state in mice. Free Radic Biol Med 35: 626-635, 2003. (Pubitemid 37101130)
265. Rebrin I and Sohal RS. Comparison of thiol redox state of mitochondria and homogenates of various tissues between two strains of mice with different longevities. Exp Gerontol 39: 1513-1519, 2004. (Pubitemid 39410551)
266. Redfield MM, Rodeheffer RJ, Jacobsen SJ, Mahoney DW, Bailey KR, and Burnett JC, Jr. Plasma brain natriuretic peptide concentration: impact of age and gender. J Am Coll Cardiol 40: 976-982, 2002. (Pubitemid 34994995)
267. Remondino A, Kwon SH, Communal C, Pimentel DR, Sawyer DB, Singh K, and Colucci WS. Beta-adrenergic receptor-stimulated apoptosis in cardiac myocytes is mediated by reactive oxygen species/c-Jun NH2-terminal kinase-dependent activation of the mitochondrial pathway. Circ Res 92: 136-138, 2003. (Pubitemid 36254269)
268. Reznick RM, Zong H, Li J, Morino K, Moore IK, Yu HJ, Liu ZX, Dong J, Mustard KJ, Hawley SA, Befroy D, Pypaert M, Hardie DG, Young LH, and Shulman GI. Aging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis. Cell Metab 5: 151-156, 2007. (Pubitemid 46172924)
269. Riordan MM, Weiss EP, Meyer TE, Ehsani AA, Racette SB, Villareal DT, Fontana L, Holloszy JO, and Kovacs SJ. The effects of caloric restriction-and exercise-induced weight loss on left ventricular diastolic function. Am J Physiol Heart Circ Physiol 294: H1174-H1182, 2008. (Pubitemid 351468712)
270. Ristow M and Zarse K. How increased oxidative stress promotes longevity and metabolic health: the concept of mitochondrial hormesis (mitohormesis). Exp Gerontol 45: 410-418, 2010.
271. Ristow M, Zarse K, Oberbach A, Kloting N, Birringer M, Kiehntopf M, Stumvoll M, Kahn CR, and Bluher M. Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci USA 106: 8665-8670, 2009.
272. Rodrigo R, Miranda A, and Vergara L. Modulation of endogenous antioxidant system by wine polyphenols in human disease. Clin Chim Acta 412: 410-424, 2011.
273. Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, Carnethon MR, Dai S, de Simone G, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Greenlund KJ, Hailpern SM, Heit JA, Michael Ho P, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, McDermott MM, Meigs JB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Rosamond WD, Sorlie PD, Stafford RS, Turan TN, Turner MB, Wong ND, and Wylie-Rosett J. Executive Summary: Heart Disease and Stroke Statistics-2011 Update: A Report From the American Heart Association. Circulation 123: 459-463, 2011.
274. Rohde LE, Ducharme A, Arroyo LH, Aikawa M, Sukhova GH, Lopez-Anaya A, McClure KF, Mitchell PG, Libby P, and Lee RT. Matrix metalloproteinase inhibition attenuates early left ventricular enlargement after experimental myocardial infarction in mice. Circulation 99: 3063-3070, 1999. (Pubitemid 29270438)
275. Rohrbach S, Niemann B, Abushouk AM, and Holtz J. Caloric restriction and mitochondrial function in the ageing myocardium. Exp Gerontol 41: 525-531, 2006. (Pubitemid 43765903)
276. RonnebaumSMand Patterson C. The FoxO family in cardiac function and dysfunction. Annu Rev Physiol 72: 81-94, 2010.
277. Rossignol R, Malgat M, Mazat JP, and Letellier T. Threshold effect and tissue specificity. Implication for mitochondrial cytopathies. J Biol Chem 274: 33426-33432, 1999. (Pubitemid 129511648)
278. Rota M, LeCapitaine N, Hosoda T, Boni A, De Angelis A, Padin-Iruegas ME, Esposito G, Vitale S, Urbanek K, Casarsa C, Giorgio M, Luscher TF, Pelicci PG, Anversa P, Leri A, and Kajstura J. Diabetes promotes cardiac stem cell aging and heart failure, which are prevented by deletion of the p66shc gene. Circ Res 99: 42-52, 2006. (Pubitemid 44297054)
279. Roth GS, Mattison JA, Ottinger MA, Chachich ME, Lane MA, and Ingram DK. Aging in rhesus monkeys: relevance to human health interventions. Science 305: 1423-1426, 2004. (Pubitemid 39167653)
280. Rudolph KL, Chang S, Lee HW, Blasco M, Gottlieb GJ, Greider C, and DePinho RA. Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell 96: 701-712, 1999. (Pubitemid 29122812)
281. Sachs HG, Colgan JA, and Lazarus ML. Ultrastructure of the aging myocardium: a morphometric approach. Am J Anat 150: 63-71, 1977. (Pubitemid 8209937)
282. Sadoshima J, Qiu Z, Morgan JP, and Izumo S. Angiotensin II and other hypertrophic stimuli mediated by G proteincoupled receptors activate tyrosine kinase,mitogen-activated protein kinase, and 90-kD S6 kinase in cardiacmyocytes. The critical role of Ca(2 + )-dependent signaling. Circ Res 76: 1-15, 1995.
283. Safdar A, Bourgeois JM, Ogborn DI, Little JP, Hettinga BP, Akhtar M, Thompson JE, Melov S, Mocellin NJ, Kujoth GC, Prolla TA, and Tarnopolsky MA. Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice. Proc Natl Acad Sci USA, 2011.
284. Sangaralingham SJ, Huntley BK, Martin FL, McKie PM, Bellavia D, Ichiki T, Harders GE, Chen HH, and Burnett JC, Jr. The aging heart, myocardial fibrosis, and its relationship to circulating C-type natriuretic Peptide. Hypertension 57: 201-207, 2011.
285. Sauve AA, Cahill SM, Zech SG, Basso LA, Lewandowicz A, Santos DS, Grubmeyer C, Evans GB, Furneaux RH, Tyler PC, McDermott A, Girvin ME, and Schramm VL. Ionic states of substrates and transition state analogues at the catalytic sites of N-ribosyltransferases. Biochemistry 42: 5694-5705, 2003. (Pubitemid 36582860)
286. Sauve AA, Celic I, Avalos J, Deng H, Boeke JD, and Schramm VL. Chemistry of gene silencing: the mechanism of NAD+-dependent deacetylation reactions. Biochemistry 40: 15456-15463, 2001. (Pubitemid 34015172)
287. Sauve AA and Schramm VL. Sir2 regulation by nicotinamide results from switching between base exchange and deacetylation chemistry. Biochemistry 42: 9249-9256, 2003. (Pubitemid 36959231)
288. Scatena R, Bottoni P, Botta G, Martorana GE, and Giardina B. The role of mitochondria in pharmacotoxicology: a reevaluation of an old, newly emerging topic. Am J Physiol Cell Physiol 293: C12-C21, 2007. (Pubitemid 47105003)
289. Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, Wallace DC, and Rabinovitch PS. Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308: 1909-1911, 2005. (Pubitemid 40941874)
290. Schulz TJ, Zarse K, Voigt A, Urban N, Birringer M, and Ristow M. Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell Metab 6: 280-293, 2007. (Pubitemid 47468090)
291. Seymour EM, Parikh RV, Singer AA, and Bolling SF. Moderate calorie restriction improves cardiac remodeling and diastolic dysfunction in the Dahl-SS rat. J Mol Cell Cardiol 41: 661-668, 2006. (Pubitemid 44376792)
292. Shinmura K. Cardiovascular protection afforded by caloric restriction: essential role of nitric oxide synthase. Geriatr Gerontol Int 11: 143-156, 2011.
293. Shinmura K, Tamaki K, and Bolli R. Impact of 6-mo caloric restriction on myocardial ischemic tolerance: possible involvement of nitric oxide-dependent increase in nuclear Sirt1. Am J Physiol Heart Circ Physiol 295: H2348-H2355, 2008.
294. Shinmura K, Tamaki K, Sano M, Murata M, Yamakawa H, Ishida H, and Fukuda K. Impact of long-term caloric restriction on cardiac senescence: caloric restriction ameliorates cardiac diastolic dysfunction associated with aging. J Mol Cell Cardiol 50: 117-127, 2011.
295. Shioi T, McMullen JR, Tarnavski O, Converso K, Sherwood MC, Manning WJ, and Izumo S. Rapamycin attenuates load-induced cardiac hypertrophy in mice. Circulation 107: 1664-1670, 2003. (Pubitemid 36397337)
296. Shiojima I, Sato K, Izumiya Y, Schiekofer S, Ito M, Liao R, Colucci WS, Walsh K. Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure. J Clin Invest 115: 2108-2118, 2005. (Pubitemid 41134152)
297. Shono M, Yoshimura M, Nakayama M, Yamamuro M, Abe K, Suzuki S,Mizuno Y, Sugiyama S, Saito Y, Nakao K, Yasue H, and Ogawa H. Predominant effect of A-type natriuretic peptide on reduction of oxidative stress during the treatment of patients with heart failure. Circ J 71: 1040-1046, 2007. (Pubitemid 46998017)
298. Skulachev VP, Anisimov VN, Antonenko YN, Bakeeva LE, Chernyak BV, Erichev VP, Filenko OF, Kalinina NI, Kapelko VI, Kolosova NG, Kopnin BP, Korshunova GA, Lichinitser MR, Obukhova LA, Pasyukova EG, Pisarenko OI, Roginsky VA, Ruuge EK, Senin, II, Severina, II, Skulachev MV, Spivak IM, Tashlitsky VN, Tkachuk VA, Vyssokikh MY, Yaguzhinsky LS, and Zorov DB. An attempt to prevent senescence: a mitochondrial approach. Biochim Biophys Acta 1787: 437-461, 2009.
299. Snow BJ, Rolfe FL, Lockhart MM, Frampton CM, O'Sullivan JD, Fung V, Smith RA, Murphy MP, and Taylor KM. A double-blind, placebo-controlled study to assess the mitochondria-targeted antioxidant MitoQ as a diseasemodifying therapy in Parkinson's disease. Mov Disord 25: 1670-1674, 2010.
300. Sohal RS and Sohal BH. Hydrogen peroxide release by mitochondria increases during aging. Mech Ageing Dev 57: 187-202, 1991.
301. Spinale FG. Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function. Physiol Rev 87: 1285-1342, 2007. (Pubitemid 350041472)
302. St-Pierre J, Drori S, Uldry M, Silvaggi JM, Rhee J, Jager S, Handschin C, Zheng K, Lin J, Yang W, Simon DK, Bachoo R, and Spiegelman BM. Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 127: 397-408, 2006. (Pubitemid 44572377)
303. Stahl M, Dijkers PF, Kops GJ, Lens SM, Coffer PJ, Burgering BM, and Medema RH. The forkhead transcription factor FoxO regulates transcription of p27Kip1 and Bim in response to IL-2. J Immunol 168: 5024-5031, 2002. (Pubitemid 34495965)
304. Stein M, Boulaksil M, Jansen JA, Herold E, Noorman M, Joles JA, van Veen TA, Houtman MJ, Engelen MA, Hauer RN, de Bakker JM, and van Rijen HV. Reduction of fibrosisrelated arrhythmias by chronic renin-angiotensin-aldosterone system inhibitors in an aged mouse model. Am J Physiol Heart Circ Physiol 299: H310-H321, 2010.
305. Steinhubl SR. Why have antioxidants failed in clinical trials? Am J Cardiol 101: 14D-19D, 2008.
306. Stewart BF, Siscovick D, Lind BK, Gardin JM, Gottdiener JS, Smith VE, Kitzman DW, and Otto CM. Clinical factors associated with calcific aortic valve disease. Cardiovascular health study. J Am Coll Cardiol 29: 630-634, 1997. (Pubitemid 27116107)
307. Sulaiman M, Matta MJ, Sunderesan NR, Gupta MP, Periasamy M, and Gupta M. Resveratrol, an activator of SIRT1, upregulates sarcoplasmic calcium ATPase and improves cardiac function in diabetic cardiomyopathy. Am J Physiol Heart Circ Physiol 298: H833-H843, 2010.
308. Sundaresan NR, Gupta M, Kim G, Rajamohan SB, Isbatan A, and Gupta MP. Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. J Clin Invest 119: 2758-2771, 2009.
309. Supinski GS, Murphy MP, and Callahan LA. MitoQ administration prevents endotoxin-induced cardiac dysfunction. Am J Physiol Regul Integr Comp Physiol 297: R1095-R1102, 2009.
310. Szeto HH. Development of mitochondria-targeted aromatic-cationic peptides for neurodegenerative diseases. Ann N Y Acad Sci 1147: 112-121, 2008.
311. Szeto HH. Mitochondria-targeted cytoprotective peptides for ischemia-reperfusion injury. Antioxid Redox Signal 10: 601-619, 2008.
312. Szeto HH, Schiller PW, Zhao K, and Luo G. Fluorescent dyes alter intracellular targeting and function of cell-penetrating tetrapeptides. FASEB J 19: 118-120, 2005. (Pubitemid 40069937)
313. Taffet GE, Pham TT, and Hartley CJ. The age-associated alterations in late diastolic function in mice are improved by caloric restriction. J Gerontol A Biol Sci Med Sci 52: B285-B290, 1997. (Pubitemid 28006991)
314. Taghli-Lamallem O, Akasaka T, Hogg G, Nudel U, Yaffe D, Chamberlain JS, Ocorr K, and Bodmer R. Dystrophin deficiency in Drosophila reduces lifespan and causes a dilated cardiomyopathy phenotype. Aging Cell 7: 237-249, 2008. (Pubitemid 351359656)
315. Takemoto KA, Bernstein L, Lopez JF, Marshak D, Rahimtoola SH, and Chandraratna PA. Abnormalities of diastolic filling of the left ventricle associated with aging are less pronounced in exercise-trained individuals. Am Heart J 124: 143-148, 1992.
316. Tani M, Honma Y, Hasegawa H, and Tamaki K. Direct activation of mitochondrial K(ATP) channels mimics preconditioning but protein kinase C activation is less effective in middle-aged rat hearts. Cardiovasc Res 49: 56-68, 2001.
317. Tatar M, Kopelman A, Epstein D, Tu MP, Yin CM, and Garofalo RS. A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science 292: 107-110, 2001. (Pubitemid 32289137)
318. Terman A and Brunk UT. The aging myocardium: roles of mitochondrial damage and lysosomal degradation. Heart Lung Circ 14: 107-114, 2005. (Pubitemid 40895299)
319. Terman A, Gustafsson B, and Brunk UT. The lysosomalmitochondrial axis theory of postmitotic aging and cell death. Chem Biol Interact 163: 29-37, 2006. (Pubitemid 44572212)
320. Terman A, Gustafsson B, and Brunk UT. Autophagy, organelles and ageing. J Pathol 211: 134-143, 2007. (Pubitemid 46195512)
321. Terman A, Kurz T, Gustafsson B, and Brunk UT. The involvement of lysosomes in myocardial aging and disease. Curr Cardiol Rev 4: 107-115, 2008.
322. Terman A, Kurz T, Navratil M, Arriaga EA, and Brunk UT. Mitochondrial turnover and aging of long-lived postmitotic cells: the mitochondrial-lysosomal axis theory of aging. Antioxid Redox Signal 12: 503-535, 2010.
323. Terzioglu M and Larsson NG. Mitochondrial dysfunction in mammalian ageing. Novartis Found Symp 287: 197-208; discussion 208-213, 2007.
324. Trifunovic A and Larsson NG. Mitochondrial dysfunction as a cause of ageing. J Intern Med 263: 167-178, 2008.
325. Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, Bruder CE, Bohlooly YM, Gidlof S, Oldfors A, Wibom R, Tornell J, Jacobs HT, and Larsson NG. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429: 417-423, 2004. (Pubitemid 38715133)
326. Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD, Walzer G, Stiles L, Haigh SE, Katz S, LasG,Alroy J,Wu M, Py BF, Yuan J, Deeney JT, Corkey BE, and Shirihai OS. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J 27: 433-446, 2008. (Pubitemid 351161653)
327. Umpierre D, Ribeiro PA, Kramer CK, Leitao CB, Zucatti AT, Azevedo MJ, Gross JL, Ribeiro JP, and Schaan BD. Physical activity advice only or structured exercise training and association with HbA1c levels in type 2 diabetes: a systematic review and meta-analysis. JAMA 305: 1790-1799, 2011.
328. van Empel VP, Bertrand AT, van Oort RJ, van der Nagel R, Engelen M, van Rijen HV, Doevendans PA, Crijns HJ, Ackerman SL, Sluiter W, and De Windt LJ. EUK-8, a superoxide dismutase and catalase mimetic, reduces cardiac oxidative stress and ameliorates pressure overload-induced heart failure in the harlequin mouse mutant. J Am Coll Cardiol 48: 824-832, 2006. (Pubitemid 44175721)
329. Van Raamsdonk JM and Hekimi S. Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in Caenorhabditis elegans. PLoS Genet 5: e1000361, 2009.
330. Varady KA and Hellerstein MK. Alternate-day fasting and chronic disease prevention: a review of human and animal trials. Am J Clin Nutr 86: 7-13, 2007. (Pubitemid 47041587)
331. Vasan RS, Demissie S, Kimura M, Cupples LA, Rifai N, White C, Wang TJ, Gardner JP, Cao X, Benjamin EJ, Levy D, and Aviv A. Association of Leukocyte Telomere Length With Circulating Biomarkers of the Renin-Angiotensin-Aldosterone System. The Framingham Heart Study. Circulation 117:1138-1144, 2008. (Pubitemid 351544068)
332. Vasan RS, Sullivan LM, D'Agostino RB, Roubenoff R, Harris T, Sawyer DB, Levy D, and Wilson PW. Serum insulin-like growth factor I and risk for heart failure in elderly individuals without a previous myocardial infarction: the FraminghamHeart Study. Ann InternMed 139: 642-648, 2003.
333. Ventura-Clapier R, Garnier A, and Veksler V. Transcriptional control of mitochondrial biogenesis: the central role of PGC-1alpha. Cardiovasc Res 79: 208-217, 2008. (Pubitemid 351951611)
334. Vergeade A, Mulder P, Vendeville-Dehaudt C, Estour F, Fortin D, Ventura-Clapier R, Thuillez C, and Monteil C. Mitochondrial impairment contributes to cocaine-induced cardiac dysfunction: prevention by the targeted antioxidant MitoQ. Free Radic Biol Med 49: 748-756, 2010.
335. Vermulst M, Wanagat J, Kujoth GC, Bielas JH, Rabinovitch PS, Prolla TA, and Loeb LA. DNA deletions and clonal mutations drive premature aging in mitochondrial mutator mice. Nat Genet 40: 392-394, 2008. (Pubitemid 351450885)
336. Vivekananthan DP, Penn MS, Sapp SK, Hsu A, and Topol EJ. Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet 361: 2017-2023, 2003. (Pubitemid 36695043)
337. Wadden TA, Berkowitz RI, Womble LG, Sarwer DB, Phelan S, Cato RK, Hesson LA, Osei SY, Kaplan R, and Stunkard AJ. Randomized trial of lifestyle modification and pharmacotherapy for obesity. N Engl J Med 353: 2111-2120, 2005. (Pubitemid 41653103)
338. Wanagat J, Cao Z, Pathare P, and Aiken JM. Mitochondrial DNA deletion mutations colocalize with segmental electron transport system abnormalities, muscle fiber atrophy, fiber splitting, and oxidative damage in sarcopenia. FASEB J 15: 322-332, 2001. (Pubitemid 32141424)
339. Wang Z, Huang Y, Zou J, Cao K, Xu Y, and Wu JM. Effects of red wine and wine polyphenol resveratrol on platelet aggregation in vivo and in vitro. Int J Mol Med 9: 77-79, 2002.
340. Wang Z, Zou J, Cao K, Hsieh TC, Huang Y, and Wu JM. Dealcoholized red wine containing known amounts of resveratrol suppresses atherosclerosis in hypercholesterolemic rabbits without affecting plasma lipid levels. Int J Mol Med 16: 533-540, 2005.
341. Weiss RG, Gerstenblith G, and Bottomley PA. ATP flux through creatine kinase in the normal, stressed, and failing human heart. Proc Natl Acad Sci USA 102: 808-813, 2005. (Pubitemid 40282747)
342. Wen CP, Wai JP, Tsai MK, Yang YC, Cheng TY, Lee MC, Chan HT, Tsao CK, Tsai SP, and Wu X. Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study. Lancet 378: 1244-1253, 2011.
343. Wencker D, Chandra M, Nguyen K, Miao W, Garantziotis S, Factor SM, Shirani J, Armstrong RC, and Kitsis RN. A mechanistic role for cardiac myocyte apoptosis in heart failure. J Clin Invest 111: 1497-1504, 2003. (Pubitemid 38063282)
344. Wessells R, Hayes M, and Bodmer R. Cardiac functional decline with age is dependent upon regulation of 4EBP activity in the myocardium. A Dros Res Conf 48: 882C, 2007.
345. Wessells RJ, Fitzgerald E, Cypser JR, Tatar M, and Bodmer R. Insulin regulation of heart function in aging fruit flies. Nat Genet 36: 1275-1281, 2004. (Pubitemid 39577935)
346. Whiteman M, Spencer JP, Szeto HH, and Armstrong JS. Do mitochondriotropic antioxidants prevent chlorinative stress-induced mitochondrial and cellular injury? Antioxid Redox Signal 10: 641-650, 2008.
347. Wohlgemuth SE, Julian D, Akin DE, Fried J, Toscano K, Leeuwenburgh C, and Dunn WA, Jr. Autophagy in the heart and liver during normal aging and calorie restriction. Rejuvenation Res 10: 281-292, 2007. (Pubitemid 47378708)
348. Wolf MJ, Amrein H, Izatt JA, Choma MA, Reedy MC, and Rockman HA. Drosophila as a model for the identification of genes causing adult human heart disease. Proc Natl Acad Sci USA 103: 1394-1399, 2006. (Pubitemid 43191176)
349. Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, and Sinclair D. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 430: 686-689, 2004. (Pubitemid 39061685)
350. Wu D, Soong Y, Zhao GM, and Szeto HH. A highly potent peptide analgesic that protects against ischemia-reperfusioninduced myocardial stunning. Am J Physiol Heart Circ Physiol 283: H783-H791, 2002. (Pubitemid 34790875)
351. Yan L, Vatner DE, O'Connor JP, Ivessa A, Ge H, Chen W, Hirotani S, Ishikawa Y, Sadoshima J, and Vatner SF. Type 5 adenylyl cyclase disruption increases longevity and protects against stress. Cell 130: 247-258, 2007. (Pubitemid 47081133)
352. Younes A, Boluyt MO, O'Neill L, Meredith AL, Crow MT, and Lakatta EG. Age-associated increase in rat ventricular ANP gene expression correlates with cardiac hypertrophy. Am J Physiol 269: H1003-H1008, 1995.
353. Zhang C, Bills M, Quigley A, Maxwell RJ, Linnane AW, and Nagley P. Varied prevalence of age-associated mitochondrial DNA deletions in different species and tissues: a comparison between human and rat. Biochem Biophys Res Commun 230: 630-635, 1997. (Pubitemid 27225588)
354. Zhang Y, Ikeno Y, QiW, ChaudhuriA, Li Y, BokovA, Thorpe SR, Baynes JW, Epstein C, Richardson A, and Van Remmen H. Mice deficient in both Mn superoxide dismutase and glutathione peroxidase-1 have increased oxidative damage and a greater incidence of pathology but no reduction in longevity. J Gerontol A Biol Sci Med Sci: 1-9, 2009.
355. Zhao K, Luo G, Giannelli S, and Szeto HH. Mitochondriatargeted peptide prevents mitochondrial depolarization and apoptosis induced by tert-butyl hydroperoxide in neuronal cell lines. Biochem Pharmacol 70: 1796-1806, 2005. (Pubitemid 41612010)
356. Zhao K, Zhao GM, Wu D, Soong Y, Birk AV, Schiller PW, and Szeto HH. Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. J Biol Chem 279: 34682-34690, 2004. (Pubitemid 39318098)
357. Zhou B, Wu LJ, Li LH, Tashiro S, Onodera S, Uchiumi F, and Ikejima T. Silibinin protects against isoproterenol-induced rat cardiac myocyte injury through mitochondrial pathway after up-regulation of SIRT1. J Pharmacol Sci 102: 387-395, 2006. (Pubitemid 44954598)
358. Zhu H, Tannous P, Johnstone JL, Kong Y, Shelton JM, Richardson JA, Le V, Levine B, Rothermel BA, and Hill JA. Cardiac autophagy is a maladaptive response to hemodynamic stress. J Clin Invest 117: 1782-1793, 2007. (Pubitemid 47036312)
359. Zid BM, Rogers AN, Katewa SD, Vargas MA, Kolipinski MC, Lu TA, Benzer S, and Kapahi P. 4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in Drosophila. Cell 139: 149-160, 2009.
360. Zorov DB, Juhaszova M, and Sollott SJ. Mitochondrial ROS-induced ROS release: an update and review. Biochim Biophys Acta 1757: 509-517, 2006.