Skip to main content

Aging and the Frontier Ahead

  • Chapter
Aging and the Heart

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Jazwinski SM. New clues to old yeast. Mech Ageing Dev 2001;122:865–882

    PubMed  CAS  Google Scholar 

  2. Johnson TE. A personal retrospective on the genetics of aging. Biogerontology 2002;3:7–12

    PubMed  CAS  Google Scholar 

  3. Tower J. Transgenic methods for increasing Drosophila life span. Mech Ageing Dev 2000;118:1–14

    PubMed  CAS  Google Scholar 

  4. Hasty P, Vijg J. Accelerating aging by mouse reverse genetics: a rational approach to understanding longevity. Aging Cell 2004;3:55–65

    PubMed  CAS  Google Scholar 

  5. Liang H, Masoro EJ, Nelson JF, Strong R, McMahan CA, Richardson A. Genetic mouse models of extended life span. Exp Gerontol 2003;38:1353–1364

    PubMed  CAS  Google Scholar 

  6. Miller RA. Genetic approaches to the study of aging. J Am Geriatr Soc 2005;53:S284–S286

    PubMed  Google Scholar 

  7. Haigis MC, Guarente LP. Mammalian sirtuins – emerging roles in physiology, aging, and calorie restriction. Genes Dev 2006;20:2913–2921

    PubMed  CAS  Google Scholar 

  8. Bordone L, Guarente L. Calorie restriction, SIRT1 and metabolism: understanding longevity. Nat Rev Mol Cell Biol 2005;6:298–305

    PubMed  CAS  Google Scholar 

  9. Warner HR. Subfield history: use of model organisms in the search for human aging genes. Sci Aging Knowledge Environ 2003;2003(6):RE1

    PubMed  Google Scholar 

  10. Butler RN, Austad SN, Barzilai N, Braun A, Helfand S, Larsen PL, McCormick AM, Perls TT, Shuldiner AR, Sprott RL, Warner HR. Longevity genes: from primitive organisms to humans. J Gerontol A Biol Sci Med Sci 2003;58:581–584

    PubMed  Google Scholar 

  11. de Haan G, Williams RW. A genetic and genomic approach to identify longevity genes in mice. Mech Ageing Dev 2005;126:133–138

    PubMed  Google Scholar 

  12. Ocorr K, Akasaka T, Bodmer R. Age-related cardiac disease model of Drosophila. Mech Ageing Dev 2007;128:112–116

    PubMed  CAS  Google Scholar 

  13. Wessells RJ, Bodmer R. Age-related cardiac deterioration: insights from Drosophila. Front Biosci 2007;12:39–48

    PubMed  CAS  Google Scholar 

  14. Bienengraeber M, Olson TM, Selivanov VA, Kathmann EC, O’Cochlain F, Gao F, Karger AB, Ballew JD, Hodgson DM, Zingman LV, Pang YP, Alekseev AE, Terzic A. ABCC9 mutations identified in human dilated cardiomyopathy disrupt catalytic KATP channel gating. Nat Genet 2004;36:382–387

    PubMed  CAS  Google Scholar 

  15. Hekimi S. How genetic analysis tests theories of animal aging. Nat Genet 2006;38:985–991

    PubMed  CAS  Google Scholar 

  16. King MC, Marks JH, Mandell JB. New York breast cancer study group. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 2003;302:643–646

    PubMed  CAS  Google Scholar 

  17. Barzilai N, Atzmon G, Schechter C, Schaefer EJ, Cupples AL, Lipton R, Cheng S, Shuldiner AR. Unique lipoprotein phenotype and genotype associated with exceptional longevity. JAMA 2003;290:2030–2040

    PubMed  CAS  Google Scholar 

  18. Geesaman BJ, Benson E, Brewster SJ, Kunkel LM, Blanche H, Thomas G, Perls TT, Daly MJ, Puca AA. Haplotype-based identification of a microsomal transfer protein marker associated with the human life span. Proc Natl Acad Sci USA 2003;100:14115–14120

    PubMed  CAS  Google Scholar 

  19. Gerdes LU, Jeune B, Ranberg KA, Nybo H, Vaupel JW. Estimation of apolipoprotein E genotype-specific relative mortality risks from the distribution of genotypes in centenarians and middle-aged men: apolipoprotein E gene is a “frailty gene”, not a “longevity gene”. Genet Epidemiol 2000;19:202–210

    PubMed  CAS  Google Scholar 

  20. Atzmon G, Rincon M, Schechter CB, Shuldiner AR, Lipton RB, Bergman A, Barzilai N. Lipoprotein genotype and conserved pathway for exceptional longevity in humans. PLoS Biol 2006;4:e113

    PubMed  Google Scholar 

  21. Ershler WB, Keller ET. Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. Annu Rev Med 2000;51:245–270

    PubMed  CAS  Google Scholar 

  22. Pletcher SD, Khazaeli AA, Curtsinger JW. Why do life spans differ? Partitioning mean longevity differences in terms of age-specific mortality parameters. J Gerontol A Biol Sci Med Sci 2000;55:B381–B389

    PubMed  CAS  Google Scholar 

  23. Terry DF, Wilcox M, McCormick MA, Lawler E, Perls TT. Cardiovascular advantages among the offspring of centenarians. J Gerontol A Biol Sci Med Sci 2003;58:M425–M431

    PubMed  Google Scholar 

  24. Nebel A, Schreiber S. GEHA – the pan-European “Genetics of Healthy Aging” project. Sci Aging Knowledge Environ 2004;2004:pe23

    Google Scholar 

  25. Puca AA, Daly MJ, Brewster SJ, Matise TC, Barrett J, Shea-Drinkwater M, Kang S, Joyce E, Nicoli J, Benson E, Kunkel LM, Perls T. A genome-wide scan for linkage to human exceptional longevity identifies a locus on chromosome 4. Proc Natl Acad Sci USA 2001;98:10505–10508

    PubMed  CAS  Google Scholar 

  26. Nebel A, Crouchr PJ, Stiegeler R, Nikolaus S, Krawczak M, Schreiber S. No association between microsomal triglyceride transfer protein (MTP) haplotype and longevity in humans. Proc Natl Acad Sci USA 2005;102:7906–7909

    PubMed  CAS  Google Scholar 

  27. Candore G, Balistreri CR, Listi F, Grimaldi MP, Vasto S, Colonna-Romano G, Franceschi C, Lio D, Caselli G, Caruso C. Immunogenetics, gender, and longevity. Ann NY Acad Sci 2006;1089:516–537

    PubMed  Google Scholar 

  28. De Benedictis G, Tan Q, Jeune B, Christensen K, Ukraintseva SV, Bonafe M, Franceschi C, Vaupel JW, Yashin AI. Recent advances in human gene-longevity association studies. Mech Ageing Dev 2001;122:909–920

    PubMed  Google Scholar 

  29. Melzer D, Hurst AJ, Frayling T. Genetic variation and human aging: progress and prospects. J Gerontol A Biol Sci Med Sci 2007;62:301–307

    PubMed  Google Scholar 

  30. Tan Q, Kruse TA, Christensen K. Design and analysis in genetic studies of human ageing and longevity. Ageing Res Rev 2006;5:371–387

    PubMed  CAS  Google Scholar 

  31. Tan Q, Christiansen L, Bathum L, Li S, Kruse TA, Christensen K. Genetic association analysis of human longevity in cohort studies of elderly subjects: an example of the PON1 gene in the Danish 1905 birth cohort. Genetics 2006;172:1821–1828

    PubMed  CAS  Google Scholar 

  32. Singh R, Kolvraa S, Bross P, Christensen K, Gregersen N, Tan Q, Jensen UB, Eiberg H, Rattan SI. Heat-shock protein 70 genes and human longevity: a view from Denmark. Ann NY Acad Sci 2006;1067:301–308

    PubMed  CAS  Google Scholar 

  33. Martin GM. Genetic modulation of senescent phenotypes in homo sapiens. Cell 2005;120:523–532

    PubMed  CAS  Google Scholar 

  34. Zhang J, Asin-Cayuela J, Fish J, Michikawa Y, Bonafe M, Olivieri F, Passarino G, De Benedictis G, Franceschi C, Attardi G. Strikingly higher frequency in centenarians and twins of mtDNA mutation causing remodeling of replication origin in leukocytes. Proc Natl Acad Sci USA 2003;100:1116–1121

    PubMed  CAS  Google Scholar 

  35. Niemi AK, Moilanen JS, Tanaka M, Hervonen A, Hurme M, Lehtimaki T, Arai Y, Hirose N, Majamaa K. A combination of three common inherited mitochondrial DNA polymorphisms promotes longevity in Finnish and Japanese subjects. Eur J Hum Genet 2005;13:166–170

    PubMed  CAS  Google Scholar 

  36. Ross OA, McCormack R, Curran MD, Duguid RA, Barnett YA, Rea IM, Middleton D. Mitochondrial DNA polymorphism: its role in longevity of the Irish population. Exp Gerontol 2001;36:1161–1178

    PubMed  CAS  Google Scholar 

  37. Santoro A, Salvioli S, Raule N, Capri M, Sevini F, Valensin S, Monti D, Bellizzi D, Passarino G, Rose G, De Benedictis G, Franceschi C. Mitochondrial DNA involvement in human longevity. Biochim Biophys Acta 2006;1757:1388–1399

    PubMed  CAS  Google Scholar 

  38. Merriwether DA, Clark AG, Ballinger SW, Schurr TG, Soodyall H, Jenkins T, Sherry ST, Wallace DC. The structure of human mitochondrial DNA variation. J Mol Evol 1991;33:543–555

    PubMed  CAS  Google Scholar 

  39. De Benedictis G, Rose G, Carrieri G, De Luca M, Falcone E, Passarino G, Bonafe M, Monti D, Baggio G, Bertolini S, Mari D, Mattace R, Franceschi C. Mitochondrial DNA inherited variants are associated with successful aging and longevity in humans. FASEB 1999;13:1532–1536

    Google Scholar 

  40. Niemi AK, Hervonen A, Hurme M, Karhunen PJ, Jylha M, Majamaa K. Mitochonrial DNA polymorphisms associated with longevity in a Finnish population. Hum Genet 2003;112:29–33

    PubMed  CAS  Google Scholar 

  41. Dato S, Passarino G, Rose G, Altomare K, Bellizzi D, Mari V, Feraco E, Franceschi C, De Benedictis G. Association of the mitochondrial DNA haplogroup J with longevity is population specific. Eur J Hum Genet 2004;12:1080–1082

    PubMed  CAS  Google Scholar 

  42. Brown MD, Starikovskaya E, Derbeneva O, Hosseini S, Allen JC, Mikhailovskaya IE, Sukernik RI, Wallace DC. The role of mtDNA background in disease expression: a new primary LHON mutation associated with Western Eurasian haplogroup. J Hum Genet 2002;110:130–138

    CAS  Google Scholar 

  43. Torroni A, Petrozzi M, D’Urbano L, Sellitto D, Zeviani M, Carrara F, Carducci C, Leuzzi V, Carelli V, Barboni P, De Negri A, Scozzari R. Haplotype and phylogenetic analyses suggest that one European-specific mtDNA background plays a role in the expression of leber hereditary optic neuropathy by increasing the penetrance of the primary mutations 11778 and 14484. Am J Hum Genet 1997;60:1107–1121

    PubMed  CAS  Google Scholar 

  44. Reynier P, Penisson-Besnier I, Moreau C, Savagner F, Vielle B, Emile J, Dubas F, Malthiery Y. mtDNA haplogroup J: a contributing factor of optic neuritis. Eur J Hum Genet 1999;7:404–406

    PubMed  CAS  Google Scholar 

  45. Rose G, Passarino G, Carrieri G, Altomare K, Greco V, Bertolini S, Bonafe M, Franceschi C, De Benedictis G. Paradoxes in longevity: sequence analysis of mtDNA haplogroup J in centenarians. Eur J Hum Genet 2001;9:701–707

    PubMed  CAS  Google Scholar 

  46. Wallace DC. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet 2005;39:359–407

    PubMed  CAS  Google Scholar 

  47. Tanaka M, Gong JS, Zhang J, Yoneda M, Yagi K. Mitochondrial genotype associated with longevity. Lancet 1998;351:185–186

    PubMed  CAS  Google Scholar 

  48. Tanaka M, Gong J, Zhang J, Yamada Y, Borgeld HJ, Yagi K. Mitochondrial genotype associated with longevity and its inhibitory effect on mutagenesis. Mech Ageing Dev 2000;116:65–76

    PubMed  CAS  Google Scholar 

  49. Yao YG, Kong QP, Zhang YP. Mitochondrial DNA 5178A polymorphism and longevity. Hum Genet 2002;111:462–463

    PubMed  Google Scholar 

  50. Takagi K, Yamada Y, Gong JS, Sone T, Yokota M, Tanaka M. Association of a 5178C<001>A (Leu237Met) polymorphism in the mitochondrial DNA with a low prevalence of myocardial infarction in Japanese individuals. Atherosclerosis 2004;175:281–286

    PubMed  CAS  Google Scholar 

  51. Mukae S, Aoki S, Itoh S, Sato R, Nishio K, Iwata T, Katagiri T. Mitochondrial 5178A/C genotype is associated with acute myocardial infarction. Circ J 2003;67:16–20

    PubMed  CAS  Google Scholar 

  52. Wang D, Taniyama M, Suzuki Y, Katagiri T, Ban Y. Association of the mitochondrial DNA 5178A/C polymorphism with maternal inheritance and onset of type 2 diabetes in Japanese patients. Exp Clin Endocrinol Diabetes 2001;109:361–364

    PubMed  CAS  Google Scholar 

  53. Matsunaga H, Tanaka Y, Tanaka M, Gong JS, Zhang J, Nomiyama T, Ogawa O, Ogihara T, Yamada Y, Yagi K, Kawamori R. Antiatherogenic mitochondrial genotype in patients with type 2 diabetes. Diabetes Care 2001;24:500–503

    PubMed  CAS  Google Scholar 

  54. Kokaze A, Ishikawa M, Matsunaga N, Yoshida M, Sekine Y, Sekiguchi K, Harada M, Satoh M, Teruya K, Takeda N, Fukazawa S, Uchida Y, Takashima Y. Longevity-associated mitochondrial DNA 5178 A/C polymorphism and blood pressure in the Japanese population. J Hum Hypertens 2004;18:41–45

    PubMed  CAS  Google Scholar 

  55. Kokaze A, Yoshida M, Ishikawa M, Matsunaga N, Makita R, Satoh M, Sekiguchi K, Masuda Y, Uchida Y, Takashima Y. Longevity-associated mitochondrial DNA 5178 A/C polymorphism is associated with intraocular pressure in Japanese men. Clin Experiment Ophthalmol 2004;32:131–136

    PubMed  Google Scholar 

  56. Hayflick L. The longevity of cultured human cells. J Am Geriatr Soc 1974;22:1–12

    PubMed  CAS  Google Scholar 

  57. Ben-Porath I, Weinberg RA. The signals and pathways activating cellular senescence. Int J Biochem Cell Biol 2005;37:961–976

    PubMed  CAS  Google Scholar 

  58. Kregel KC, Zhang HJ. An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations. Am J Physiol Regul Integr Comp Physiol 2007;292:R18–R36

    PubMed  CAS  Google Scholar 

  59. Passos JF, von Zglinicki T. Mitochondria, telomeres and cell senescence. Exp Gerontol 2005;40:466–472

    PubMed  CAS  Google Scholar 

  60. Chevanne M, Caldini R, Tombaccini D, Mocali A, Gori G, Paoletti F. Comparative levels of DNA breaks and sensitivity to oxidative stress in aged and senescent human fibroblasts: a distinctive pattern for centenarians. Biogerontology 2003;4:97–104

    PubMed  CAS  Google Scholar 

  61. Foreman KE, Tang J. Molecular mechanisms of replicative senescence in endothelial cells. Exp Gerontol 2003;38:1251–1257

    PubMed  CAS  Google Scholar 

  62. Bekaert S, De Meyer T, Van Oostveldt P. Telomere attrition as ageing biomarker. Anticancer Res 2005;25:3011–3021

    PubMed  CAS  Google Scholar 

  63. von Zglinicki T, Martin-Ruiz CM. Telomeres as biomarkers for ageing and age-related diseases. Curr Mol Med 2005;5:197–203

    Google Scholar 

  64. Lou Z, Chen J. Cellular senescence and DNA repair. Exp Cell Res 2006;312:2641–2646

    PubMed  CAS  Google Scholar 

  65. de Magalhaes JP. From cells to ageing: a review of models and mechanisms of cellular senescence and their impact on human ageing. Exp Cell Res 2004;300:1–10

    PubMed  Google Scholar 

  66. Erusalimsky JD, Kurz DJ. Cellular senescence in vivo: its relevance in ageing and cardiovascular disease. Exp Gerontol 2005;40:634–642

    PubMed  CAS  Google Scholar 

  67. Cristofalo VJ, Lorenzini A, Allen RG, Torres C, Tresini M. Replicative senescence: a critical review. Mech Ageing Dev 2004;125:827–848

    PubMed  CAS  Google Scholar 

  68. Hornsby PJ. Cellular senescence and tissue aging in vivo. J Gerontol A Biol Sci Med Sci 2002l;57:B251–B256

    Google Scholar 

  69. Minamino T, Komuro I. Vascular cell senescence: contribution to atherosclerosis. Circ Res 2007;100:15–26

    PubMed  CAS  Google Scholar 

  70. Matthews C, Gorenne I, Scott S, Figg N, Kirkpatrick P, Ritchie A, Goddard M, Bennett M. Vascular smooth muscle cells undergo telomere-based senescence in human atherosclerosis: effects of telomerase and oxidative stress. Circ Res 2006;99:156–164

    PubMed  CAS  Google Scholar 

  71. Carlson ME, Conboy IM. Loss of stem cell regenerative capacity within aged niches. Aging Cell 2007;6:371–382

    PubMed  CAS  Google Scholar 

  72. Geiger H, Rennebeck G, Van Zant G. Regulation of hematopoietic stem cell aging in vivo by a distinct genetic element. Proc Natl Acad Sci USA 2005;102:5102–5107

    PubMed  CAS  Google Scholar 

  73. Torella D, Rota M, Nurzynska D, Musso E, Monsen A, Shiraishi I, Zias E, Walsh K, Rosenzweig A, Sussman MA, Urbanek K, Nadal-Ginard B, Kajstura J, Anversa P, Leri A. Cardiac stem cell and myocyte aging, heart failure, and insulin-like growth factor-1 overexpression. Circ Res 2004;94:514–524

    PubMed  CAS  Google Scholar 

  74. Anversa P, Kajstura J, Leri A, Bolli R. Life and death of cardiac stem cells: a paradigm shift in cardiac biology. Circulation 2006;113:1451–1463

    PubMed  Google Scholar 

  75. Butler RN, Sprott R, Warner H, Bland J, Feuers R, Forster M, Fillit H, Harman SM, Hewitt M, Hyman M, Johnson K, Kligman E, McClearn G, Nelson J, Richardson A, Sonntag W, Weindruch R, Wolf N. Biomarkers of aging: from primitive organisms to humans. J Gerontol A Biol Sci Med Sci 2004;59:B560–B567

    PubMed  Google Scholar 

  76. Johnson TE. Recent results: biomarkers of aging. Exp Gerontol 2006;41:1243–1246

    PubMed  CAS  Google Scholar 

  77. Voss P, Siems W. Clinical oxidation parameters of aging. Free Radic Res 2006;40:1339–1349

    PubMed  CAS  Google Scholar 

  78. Ochi H, Cheng RZ, Kantha SS, Takeuchi M, Ramarathnam N. The JaICA-genox oxidative stress profile – an overview on the profiling technique in the oxidative stress assessment and management. Biofactors 2000;13:195–203

    PubMed  CAS  Google Scholar 

  79. Chevion M, Berenshtein E, Stadtman ER. Human studies related to protein oxidation: protein carbonyl content as a marker of damage. Free Radic Res 2000;33:S99–S108

    PubMed  CAS  Google Scholar 

  80. DiMarco T, Giulivi C. Current analytical methods for the detection of dityrosine, a biomarker of oxidative stress, in biological samples. Mass Spectrom Rev 2007;26:108–120

    PubMed  CAS  Google Scholar 

  81. Kanski J, Behring A, Pelling J, Schoneich C. Proteomic identification of 3-nitrotyrosine-containing rat cardiac proteins: effects of biological aging. Am J Physiol Heart Circ Physiol 2005;288:H371–H381

    PubMed  CAS  Google Scholar 

  82. Pero RW, Hoppe C, Sheng Y. Serum thiols as a surrogate estimate of DNA repair correlates to mammalian life span. J Anti-Aging Med 2000;3:241–249

    CAS  Google Scholar 

  83. Yan L-J, Levine RL, Sohal RS. Oxidative damage during aging targets mitochondrial aconitase. Proc Natl Acad Sci USA 1997;94:11168–11172

    PubMed  CAS  Google Scholar 

  84. Yan L-J, Sohal RS. Mitochondrial adenine nucleotide translocase is modified oxidatively during aging. Proc Natl Acad Sci USA 1998;95:12896–12901

    PubMed  CAS  Google Scholar 

  85. Navarro A. Mitochondrial enzyme activities as biochemical markers of aging. Mol Aspects Med 2004;25:37–48

    PubMed  CAS  Google Scholar 

  86. Linton S, Davies MJ, Dean RT. Protein oxidation and ageing. Exp Gerontol 2001;36:1503–1518

    PubMed  CAS  Google Scholar 

  87. Strehler BL, Mark DD, Mildvan AS, Gee MV. Rate of magnitude of age pigment accumulation in the human myocardium. J Gerontol 1959;14:430–439

    PubMed  CAS  Google Scholar 

  88. Reichel E, Holander J, Clark HJ, Strehler BL. Lipofuscin pigment accumulation as a function of age and distribution in rodent brain. J Gerontol 1968;23:71–78

    PubMed  CAS  Google Scholar 

  89. Kato Y, Maruyama W, Naoi M, Hashizume Y, Osawa T. Immunohistochemical detection of dityrosine in lipofuscin pigments in the aged human brain. FEBS Lett 1998;439:231–234

    PubMed  CAS  Google Scholar 

  90. Sohal RS, Brunk UT. Lipofuscin as an indicator of oxidative stress and aging. Adv Exp Med Biol 1989;266:17–26

    PubMed  CAS  Google Scholar 

  91. Sitte N, Merker K, Von Zglinicki T, Davies KJ, Grune T. Protein oxidation and degradation during cellular senescence of human BJ fibroblasts: part II – aging of nondividing cells. FASEB J 2000;14:2503–2510

    PubMed  CAS  Google Scholar 

  92. Baynes JW, Thorpe SR. Glycoxidation and lipoxidation in atherogenesis. Free Radic Biol Med 2000;28:1708–1716

    PubMed  CAS  Google Scholar 

  93. Schleicher ED, Wagner E, Nerlich AG. Increased accumulation of the glycoxidation product N(epsilon)-(carboxymethyl)lysine in human tissues in diabetes and aging. J Clin Invest 1997;99:457–468

    PubMed  CAS  Google Scholar 

  94. Wautier JL, Schmidt AM. Protein glycation: a firm link to endothelial cell dysfunction. Circ Res 2004;95:233–238

    PubMed  CAS  Google Scholar 

  95. Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA 1993;90:7915–7922

    PubMed  CAS  Google Scholar 

  96. Hudson EK, Hogue BA, Souza-Pinto NC, Croteau DL, Anson RM, Bohr VA, Hansford RG. Age-associated change in mitochondrial DNA damage. Free Radic Res 1998;29:573–579

    PubMed  CAS  Google Scholar 

  97. Anson RM, Hudson E, Bohr VA. Mitochondrial endogenous oxidative damage has been overestimated. FASEB J 2000;14:355–360

    PubMed  CAS  Google Scholar 

  98. Hamilton ML, Van Remmen H, Drake JA, Yang H, Guo ZM, Kewitt K, Walter CA, Richardson A. Does oxidative damage to DNA increase with age? Proc Natl Acad Sci USA 2001;98:10469–10474

    PubMed  CAS  Google Scholar 

  99. Gianni P, Jan KJ, Douglas MJ, Stuart PM, Tarnopolsky MA. Oxidative stress and the mitochondrial theory of aging in human skeletal muscle. Exp Gerontol 2004;39:1391–1400

    PubMed  CAS  Google Scholar 

  100. Dizdaroglu M, Jaruga P, Birincioglu M, Rodriguez H. Free radical-induced damage to DNA: mechanisms and measurement. Free Radic Biol Med 2002;32:1102–1115

    PubMed  CAS  Google Scholar 

  101. Mohamed SA, Hanke T, Erasmi AW, Bechtel MJ, Scharfschwerdt M, Meissner C, Sievers HH, Gosslau A. Mitochondrial DNA deletions and the aging heart. Exp Gerontol 2006;41:508–517

    PubMed  CAS  Google Scholar 

  102. Meissner C, Bruse P, Oehmichen M. Tissue-specific deletion patterns of the mitochondrial genome with advancing age. Exp Gerontol 2006;41:518–524

    PubMed  CAS  Google Scholar 

  103. Brena RM, Huang TH, Plass C. Quantitative assessment of DNA methylation: potential applications for disease diagnosis, classification, and prognosis in clinical settings. J Mol Med 2006;84:365–377

    PubMed  CAS  Google Scholar 

  104. Wojdacz TK, Hansen LL. Techniques used in studies of age-related DNA methylation changes. Ann NY Acad Sci 2006;1067:479–487

    PubMed  CAS  Google Scholar 

  105. Bergamini E, Bizzarri R, Cavallini G, Cerbai B, Chiellini E, Donati A, Gori Z, Manfrini A, Parentini I, Signori F, Tamburini I. Ageing and oxidative stress: a role for dolichol in the antioxidant machinery of cell membranes? J Alzheimers Dis 2004;6:129–135

    PubMed  CAS  Google Scholar 

  106. Parentini I, Cavallini G, Donati A, Gori Z, Bergamini E. Accumulation of dolichol in older tissues satisfies the proposed criteria to be qualified a biomarker of aging. J Gerontol A Biol Sci Med Sci 2005;60:39–43

    PubMed  Google Scholar 

  107. Maggio M, Basaria S, Ble A, Lauretani F, Bandinelli S, Ceda GP, Valenti G, Ling SM, Ferrucci L. Correlation between testosterone and the inflammatory marker soluble interleukin-6 receptor in older men. J Clin Endocrinol Metab 2006;91:345–347

    PubMed  CAS  Google Scholar 

  108. Bellido T, Jilka RL, Boyce BF, Girasole G, Broxmeyer H, Dalrymple SA, Murray R, Broxmeyer H, Dalrymple SA, Murray R, Manolagas SC. Regulation of interleukin-6, osteoclastogenesis, and bone mass by androgens. The role of the androgen receptor. J Clin Invest 1995;95:2886–2895

    PubMed  CAS  Google Scholar 

  109. Khosla S, Atkinson EJ, Dunstan CR, O’Fallon WM. Effect of estrogen versus testosterone on circulating osteoprotegerin and other cytokine levels in normal elderly men. J Clin Endocrinol Metab 2002;87:1550–1554

    PubMed  CAS  Google Scholar 

  110. Malkin CJ, Pugh PJ, Jones RD, Kapoor D, Channer KS, Jones TH. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab 2004;89:3313–3318

    PubMed  CAS  Google Scholar 

  111. De Martinis M, Franceschi C, Monti D, Ginaldi L. Inflammation markers predicting frailty and mortality in the elderly. Exp Mol Pathol 2006;80:219–227

    PubMed  Google Scholar 

  112. Cesari M, Penninx BW, Pahor M, Lauretani F, Corsi AM, Rhys Williams G, Guralnik JM, Ferrucci L. Inflammatory markers and physical performance in older persons: the InCHIANTI study. J Gerontol A Biol Sci Med Sci 2004;59:242–248

    PubMed  Google Scholar 

  113. Kritchevsky SB, Cesari M, Pahor M. Inflammatory markers and cardiovascular health in older adults. Cardiovasc Res 2005;66:265–275

    PubMed  CAS  Google Scholar 

  114. Cesari M, Penninx BW, Newman AB, Kritchevsky SB, Nicklas BJ, Sutton-Tyrrell K, Rubin SM, Ding J, Simonsick EM, Harris TB, Pahor M. Inflammatory markers and onset of cardiovascular events: results from the health ABC study. Circulation 2003;108:2317–2322

    PubMed  CAS  Google Scholar 

  115. Lane MA, Ingram DK, Ball SS, Roth GS. Dehydroepiandrosterone sulfate: a biomarker of primate aging slowed by calorie restriction. J Clin Endocrinol Metab 1997;82:2093–2096

    PubMed  CAS  Google Scholar 

  116. Perret M, Aujard F. Aging and season affect plasma dehydroepiandrosterone sulfate (DHEA-S) levels in a primate. Exp Gerontol 2005;40:582–587

    PubMed  CAS  Google Scholar 

  117. Perrini S, Laviola L, Natalicchio A, Giorgino F. Associated hormonal declines in aging: DHEAS. J Endocrinol Invest 2005;28:85–93

    PubMed  CAS  Google Scholar 

  118. Kontoleon PE, Anastasiou-Nana MI, Papapetrou PD, Alexopoulos G, Ktenas V, Rapti AC, Tsagalou EP, Nanas JN. Hormonal profile in patients with congestive heart failure. Int J Cardiol 2003;87:179–183

    PubMed  Google Scholar 

  119. Jankowska EA, Biel B, Majda J, Szklarska A, Lopuszanska M, Medras M, Anker SD, Banasiak W, Poole-Wilson PA, Ponikowski P. Anabolic deficiency in men with chronic heart failure: prevalence and detrimental impact on survival. Circulation 2006;114:1829–1837

    PubMed  CAS  Google Scholar 

  120. Moriyama Y, Yasue H, Yoshimura M, Mizuno Y, Nishiyama K, Tsunoda R, Kawano H, Kugiyama K, Ogawa H, Saito Y, Nakao K. The plasma levels of dehydroepiandrosterone sulfate are decreased in patients with chronic heart failure in proportion to the severity. J Clin Endocrinol Metab 2000;85:1834–1840

    PubMed  CAS  Google Scholar 

  121. Feldman HA, Johannes CB, Araujo AB, Mohr BA, Longcope C, McKinlay JB. Low dehydroepiandrosterone and ischemic heart disease in middle-aged men: prospective results from the Massachusetts male aging study. Am J Epidemiol 2001;153:79–89

    PubMed  CAS  Google Scholar 

  122. Wu FC, von Eckardstein A. Androgens and coronary artery disease. Endocr Rev 2003;24:183–217

    PubMed  CAS  Google Scholar 

  123. von Muhlen D, Laughlin GA, Kritz-Silverstein D, Barrett-Connor E. The Dehydroepiandrosterone And WellNess (DAWN) study: research design and methods. Contemp Clin Trials 2007;28:153–168

    Google Scholar 

  124. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation 2002;105:1135–1143

    PubMed  CAS  Google Scholar 

  125. Davis T, Kipling D. Werner Syndrome as an example of inflamm-aging: possible therapeutic opportunities for a progeroid syndrome? Rejuvenation Res 2006;9:402–407

    PubMed  CAS  Google Scholar 

  126. Cadroy Y, Pierrejean D, Fontan B, Sie P, Boneu B. Influence of aging on the activity of the hemostatic system: prothrombin fragment 1+2, thrombin-antithrombin III complexes and D-dimers in 80 healthy subjects with age ranging from 20 to 94 years. Nouv Rev Fr Hematol 1992;34:43–46

    PubMed  CAS  Google Scholar 

  127. Pieper CF, Rao KM, Currie MS, Harris TB, Chen HJ. Age, functional status, and racial differences in plasma D-dimer levels in community-dwelling elderly persons. J Gerontol A Biol Sci Med Sci 2000;55:M649–M657

    PubMed  CAS  Google Scholar 

  128. Wilkerson WR, Sane DC. Aging and thrombosis. Semin Thromb Hemost 2002;28:555–568

    PubMed  CAS  Google Scholar 

  129. Satyanarayana A, Rudolph KL. p16 and ARF: activation of teenage proteins in old age. J Clin Invest 2004;114:1237–1240

    PubMed  CAS  Google Scholar 

  130. Shapiro GI, Edwards CD, Ewen M., Rollins BJ. p16INK4A participates in a G1 arrest checkpoint in response to DNA damage. Mol Cell Biol 1998;18:378–387

    PubMed  CAS  Google Scholar 

  131. Krishnamurthy J, Torrice C, Ramsey MR, Kovalev GI, Al-Regaiey K, Su L, Sharpless NE. Ink4a/Arf expression is a biomarker of aging. J Clin Invest 2004;114:1299–1307

    PubMed  CAS  Google Scholar 

  132. von Zglinicki T, Saretzki G, Ladhoff J, d’Adda di Fagagna F, Jackson SP. Human cell senescence as a DNA damage response. Mech Ageing Dev 2005;126:111–117

    Google Scholar 

  133. Gardner JP, Kimura M, Chai W, Durrani JF, Tchakmakjian L, Cao X, Lu X, Li G, Peppas AP, Skurnick J, Wright WE, Shay JW, Aviv A. Telomere dynamics in macaques and humans. J Gerontol A Biol Sci Med Sci 2007;62:367–374

    PubMed  Google Scholar 

  134. Kittleson MM, Hare JM. Molecular signature analysis: using the myocardial transcriptome as a biomarker in cardiovascular disease. Trends Cardiovasc Med 2005;15:130–138

    PubMed  CAS  Google Scholar 

  135. Lee CK, Klopp RG, Weindruch R, Prolla TA. Gene expression profile of aging and its retardation by caloric restriction. Science 1999;285:1390–1393

    PubMed  CAS  Google Scholar 

  136. Park SK, Prolla TA. Gene expression profiling studies of aging in cardiac and skeletal muscles. Cardiovasc Res 2005;66:205–212

    PubMed  CAS  Google Scholar 

  137. Anisimov SV, Boheler K. Aging-associated changes in cardiac gene expression: large scale transcriptome analysis. Adv Gerontol 2003;11:67–75

    PubMed  CAS  Google Scholar 

  138. Ashton KJ, Willems L, Holmgren K, Ferreira L, Headrick JP. Age-associated shifts in cardiac gene transcription and transcriptional responses to ischemic stress. Exp Gerontol 2006;41:189–204

    PubMed  CAS  Google Scholar 

  139. Edwards MG, Sarkar D, Klopp R, Morrow JD, Weindruch R, Prolla TA. Age-related impairment of the transcriptional responses to oxidative stress in the mouse heart. Physiol Genomics 2003;13:119–127

    PubMed  CAS  Google Scholar 

  140. Spindler SR. Use of microarray biomarkers to identify longevity therapeutics. Aging Cell 2006;5:39–50

    PubMed  CAS  Google Scholar 

  141. Fu C, Hickey M, Morrison M, McCarter R, Han ES. Tissue specific and non-specific changes in gene expression by aging and by early stage CR. Mech Ageing Dev 2006;127:905–916

    PubMed  CAS  Google Scholar 

  142. Bender A, Beckers J, Schneider I, Holter SM, Haack T, Ruthsatz T, Vogt-Weisenhorn DM, Becker L, Genius J, Rujescu D, Irmler M, Mijalski T, Mader M, Quintanilla-Martinez L, Fuchs H, Gailus-Durner V, de Angelis MH, Wurst W, Schmidt J, Klopstock T. Creatine improves health and survival of mice. Neurobiol Aging 2007 Apr 6; [Epub ahead of print]

    Google Scholar 

  143. Gohil K. Functional genomics identifies novel and diverse molecular targets of nutrients in vivo. Biol Chem 2004;385:691–696

    PubMed  CAS  Google Scholar 

  144. Mathers JC. Nutritional modulation of ageing: genomic and epigenetic approaches. Mech Ageing Dev 2006;127:584–589

    PubMed  CAS  Google Scholar 

  145. Feil R. Environmental and nutritional effects on the epigenetic regulation of genes. Mutat Res 2006;600:46–57

    PubMed  CAS  Google Scholar 

  146. Welle S, Brooks AI, Delehanty JM, Needler N, Thornton CA. Gene expression profile of aging in human muscle. Physiol Genomics 2003;14:149–159

    PubMed  CAS  Google Scholar 

  147. Volkova M, Garg R, Dick S, Boheler KR. Aging-associated changes in cardiac gene expression. Cardiovasc Res 2005;66:194–204

    PubMed  CAS  Google Scholar 

  148. Zahn JM, Sonu R, Vogel H, Crane E, Mazan-Mamczarz K, Rabkin R, Davis RW, Becker KG, Owen AB, Kim SK. Transcriptional profiling of aging in human muscle reveals a common aging signature. PLoS Genet 2006;2:e115

    PubMed  Google Scholar 

  149. Lu T, Pan Y, Kao SY, Li C, Kohane I, Chan J, Yankner BA. Gene regulation and DNA damage in the ageing human brain. Nature 2004;429:883–891

    PubMed  CAS  Google Scholar 

  150. Kyng KJ, May A, Stevnsner T, Becker KG, Kolvra S, Bohr VA. Gene expression responses to DNA damage are altered in human aging and in werner syndrome. Oncogen 2005;24:5026–5042

    CAS  Google Scholar 

  151. Roy AK, Oh T, Rivera O, Mubiru J, Song CS, Chatterjee B. Impacts of transcriptional regulation on aging and senescence. Ageing Res Rev 2002;1:367–380

    PubMed  CAS  Google Scholar 

  152. Kyng KJ, May A, Kolvraa S, Bohr VA. Gene expression profiling in werner syndrome closely resembles that of normal aging. Proc Natl Acad Sci USA 2003;100:12259–12264

    PubMed  CAS  Google Scholar 

  153. Kyng KJ, Bohr VA. Gene expression and DNA repair in progeroid syndromes and human aging. Ageing Res Rev 2005;4:579–602

    PubMed  CAS  Google Scholar 

  154. Csoka AB, English SB, Simkevich CP, Ginzinger DG, Butte AJ, Schatten GP, Rothman FG, Sedivy JM. Genome-scale expression profiling of Hutchinson-Gilford progeria syndrome reveals widespread transcriptional misregulation leading to mesodermal/mesenchymal defects and accelerated atherosclerosis. Aging Cell 2004;3:235–243

    PubMed  CAS  Google Scholar 

  155. Anderson L. Candidate-based proteomics in the search for biomarkers of cardiovascular disease. J Physiol 2005;563:23–60

    PubMed  CAS  Google Scholar 

  156. Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 2002;347:1557–1565

    PubMed  CAS  Google Scholar 

  157. Lopez MF, Melov S. Applied proteomics: mitochondrial proteins and effect on function. Circ Res 2002;90:380–389

    PubMed  CAS  Google Scholar 

  158. Gaucher SP, Taylor SW, Fahy E, Zhang B, Warnock DE, Ghosh SS, Gibson BW. Expanded coverage of the human heart mitochondrial proteome using multidimensional liquid chromatography coupled with tandem mass spectrometry. J Proteome Res 2004;3:495–505

    PubMed  CAS  Google Scholar 

  159. McDonald TG, Van Eyk JE. Mitochondrial proteomics. Undercover in the lipid bilayer. Basic Res Cardiol 2003;98:219–227

    PubMed  CAS  Google Scholar 

  160. Kiri AN, Tran HC, Drahos KL, Lan W, McRorie DK, Horn MJ. Proteomic changes in bovine heart mitochondria with age: using a novel technique for organelle separation and enrichment. J Biomol Tech 2005;16:371–379

    PubMed  Google Scholar 

  161. Yan L, Ge H, Li H, Lieber SC, Natividad F, Resuello RR, Kim SJ, Akeju S, Sun A, Loo K, Peppas AP, Rossi F, Lewandowski ED, Thomas AP, Vatner SF, Vatner DE. Gender-specific proteomic alterations in glycolytic and mitochondrial pathways in aging monkey hearts. J Mol Cell Cardiol 2004;37:921–929

    PubMed  CAS  Google Scholar 

  162. Dencher NA, Goto S, Reifschneider NH, Sugawa M, Krause F. Unraveling age-dependent variation of the mitochondrial proteome. Ann NY Acad Sci 2006;1067:116–119

    PubMed  CAS  Google Scholar 

  163. Reifschneider NH, Goto S, Nakamoto H, Takahashi R, Sugawa M, Dencher NA, Krause F. Defining the mitochondrial proteomes from five rat organs in a physiologically significant context using 2D blue-native/SDS-PAGE. J Proteome Res 2006;5:1117–1132

    PubMed  CAS  Google Scholar 

  164. Hunzinger C, Wozny W, Schwall GP, Poznanovic S, Stegmann W, Zengerling H, Schoepf R, Groebe K, Cahill MA, Osiewacz HD, Jagemann N, Bloch M, Dencher NA, Krause F, Schrattenholz A. Comparative profiling of the mammalian mitochondrial proteome: multiple aconitase-2 isoforms including N-formylkynurenine modifications as part of a protein biomarker signature for reactive oxidative species. J Proteome Res 2006;5:625–633

    PubMed  CAS  Google Scholar 

  165. Crampin EJ, Halstead M, Hunter P, Nielsen P, Noble D, Smith N, Tawhai M. Computational physiology and the Physiome Project. Exp Physiol 2004;89:1–26

    PubMed  Google Scholar 

  166. Kirkwood TB, Proctor CJ. Somatic mutations and ageing in silico. Mech Ageing Dev 2003;124:85–92

    PubMed  CAS  Google Scholar 

  167. Salvioli S, Capri M, Valensin S, Tieri P, Monti D, Ottaviani E, Franceschi C. Inflamm-aging, cytokines and aging: state of the art, new hypotheses on the role of mitochondria and new perspectives from systems biology. Curr Pharm Des 2006;12:3161–3171

    PubMed  CAS  Google Scholar 

  168. Bassingthwaighte JB, Qian H, Li Z. The cardiome project: an integrated view of cardiac metabolism and regional mechanical function. Adv Exp Med Biol 1999;471:541–53

    PubMed  CAS  Google Scholar 

  169. Kriete A, Sokhansanj BA, Coppock DL, West GB. Systems approaches to the networks of aging. Ageing Res Rev 2006;5:434–448

    PubMed  CAS  Google Scholar 

  170. Kriete A. Biomarkers of aging: combinatorial or systems model? Sci Aging Knowledge Environ 2006;2006:pe1

    Google Scholar 

  171. Kirkwood TB, Kowald A. Network theory of aging. Exp Gerontol 1997;32:395–399

    PubMed  CAS  Google Scholar 

  172. 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, Prolla TA. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 2005;309: 481–484

    PubMed  CAS  Google Scholar 

  173. Kirkwood TB, Boys RJ, Gillespie CS, Proctor CJ, Shanley DP, Wilkinson DJ. Towards an e-biology of ageing: integrating theory and data. Nat Rev Mol Cell Biol 2003;4:243–249

    PubMed  CAS  Google Scholar 

  174. de Magalhaes JP, Toussaint O. GenAge: a genomic and proteomic network map of human ageing. FEBS Lett 2004;571:243–247

    PubMed  Google Scholar 

  175. de Magalhaes JP, Costa J, Toussaint O. HAGR: the human ageing genomic resources. Nucleic Acids Res 2005;33:D537–D543

    PubMed  Google Scholar 

  176. Boyce K, Kriete A, Nagatomi S, Kelder B, Coschigano K, Kopchick JJ. Phenotypical enrichment strategies for microarray data analysis applied in a type II diabetes study. OMICS 2005;9:251–265

    PubMed  CAS  Google Scholar 

  177. Noble D. Modelling the heart: insights, failures and progress. Bioessays 2002;24:1155–1163

    PubMed  Google Scholar 

  178. Sastre J, Pallardo FV, Vina J. The role of mitochondrial oxidative stress in aging. Free Radic Biol Med 2003;35:1–8

    PubMed  CAS  Google Scholar 

  179. Timiras PS, Yaghmaie F, Saeed O, Thung E, Chinn G. The ageing phenome: caloric restriction and hormones promote neural cell survival, growth, and de-differentiation. Mech Ageing Dev 2005;126:3–9

    PubMed  CAS  Google Scholar 

  180. Lussier YA, Liu Y. Computational approaches to phenotyping: high-throughput phenomics. Proc Am Thorac Soc 2007;4:18–25

    PubMed  Google Scholar 

  181. Butte AJ, Kohane IS. Creation and implications of a phenome-genome network. Nat Biotechnol 2006;24:55–62

    PubMed  CAS  Google Scholar 

  182. Harris TB, Launer LJ, Eiriksdottir G, Kjartansson O, Jonsson PV, Sigurdsson G, Thorgeirsson G, Aspelund T, Garcia ME, Cotch MF, Hoffman HJ, Gudnason V. Age, gene/environment susceptibility-Reykjavik study: multidisciplinary applied phenomics. Am J Epidemiol 2007;165:1076–1087

    PubMed  Google Scholar 

  183. de Grey AD, Ames BN, Andersen JK, Bartke A, Campisi J, Heward CB, McCarter RJ, Stock G. Time to talk SENS: critiquing the immutability of human aging. Ann NY Acad Sci 2002;959:452–62

    PubMed  Google Scholar 

  184. de Grey AD, Baynes JW, Berd D, Heward CB, Pawelec G, Stock G. Is human aging still mysterious enough to be left only to scientists? Bioessays 2002;24:667–676

    PubMed  Google Scholar 

  185. de Grey AD. Challenging but essential targets for genuine anti-ageing drugs. Expert Opin Ther Targets 2003;7:1–5

    PubMed  Google Scholar 

  186. de Grey AD. Like it or not, life-extension research extends beyond biogerontology. EMBO Rep 2005;6:1000

    PubMed  Google Scholar 

  187. Warner H, Anderson J, Austad S, Bergamini E, Bredesen D, Butler R, Carnes BA, Clark BF, Cristofalo V, Faulkner J, Guarente L, Harrison DE, Kirkwood T, Lithgow G, Martin G, Masoro E, Melov S, Miller RA, Olshansky SJ, Partridge L, Pereira-Smith O, Perls T, Richardson A, Smith J, von Zglinicki T, Wang E, Wei JY, Williams TF. Science fact and the SENS agenda. What can we reasonably expect from ageing research? EMBO Rep 2005;6:1006–1008

    CAS  Google Scholar 

  188. Yamamoto S, Yang G, Zablocki D, Liu J, Hong C, Kim SJ, Soler S, Odashima M, Thaisz J, Yehia G, Molina CA, Yatani A, Vatner DE, Vatner SF, Sadoshima J. Activation of Mst1 causes dilated cardiomyopathy by stimulating apoptosis without compensatory ventricular myocyte hypertrophy. J Clin Invest 2003;111:1463–1474

    PubMed  CAS  Google Scholar 

  189. Wencker D, Chandra M, Nguyen K, Miao W, Garantziotis S, Factor SM, Shirani J, Armstrong RC, Kitsis RN. A mechanistic role for cardiac myocyte apoptosis in heart failure. J Clin Invest 2003;111:1497–1504

    PubMed  CAS  Google Scholar 

  190. Holly TA, Drincic A, Byun Y, Nakamura S, Harris K, Klocke FJ, Cryns VL. Caspase inhibition reduces myocyte cell death induced by myocardial ischemia and reperfusion in vivo. J Mol Cell Cardiol 1999;31:1709–1715

    PubMed  CAS  Google Scholar 

  191. Faubel S, Edelstein CL. Caspases as drug targets in ischemic organ injury. Curr Drug Targets Immune Endocr Metabol Disord 2005;5:269–287 191. Brocheriou V, Hagege AA, Oubenaissa A, Lambert M, Mallet VO, Duriez M, Wassef M, Kahn A, Menasche P, Gilgenkrantz H. Cardiac functional improvement by a human Bcl-2 transgene in a mouse model of ischemia/reperfusion injury. J Gene Med 2000;2:326–333

    PubMed  CAS  Google Scholar 

  192. Jayasankar V, Woo YJ, Pirolli TJ, Bish LT, Berry MF, Burdick J, Gardner TJ, Sweeney HL. Induction of angiogenesis and inhibition of apoptosis by hepatocyte growth factor effectively treats postischemic heart failure. J Card Surg 2005;20:93–101

    PubMed  Google Scholar 

  193. Haendeler J. Nitric oxide and endothelial cell aging. Eur J Clin Pharmacol 2006;62:137–140

    CAS  Google Scholar 

  194. Napoli C, Martin-Padura I, de Nigris F, Giorgio M, Mansueto G, Somma P, Condorelli M, Sica G, De Rosa G, Pelicci P. Deletion of the p66Shc longevity gene reduces systemic and tissue oxidative stress, vascular cell apoptosis, and early atherogenesis in mice fed a high-fat diet. Proc Natl Acad Sci USA 2003;100:2112–2116

    PubMed  CAS  Google Scholar 

  195. Menini S, Amadio L, Oddi G, Ricci C, Pesce C, Pugliese F, Giorgio M, Migliaccio E, Pelicci P, Iacobini C, Pugliese G. Deletion of p66Shc longevity gene protects against experimental diabetic glomerulopathy by preventing diabetes-induced oxidative stress. Diabetes 2006;55:1642–1650

    PubMed  CAS  Google Scholar 

  196. 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, Kajstura J. Diabetes promotes cardiac stem cell aging and heart failure, which are prevented by deletion of the p66shc gene. Circ Res 2006;99:42–52

    PubMed  CAS  Google Scholar 

  197. Pinton P, Rimessi A, Marchi S, Orsini F, Migliaccio E, Giorgio M, Contursi C, Minucci S, Mantovani F, Wieckowski MR, Del Sal G, Pelicci PG, Rizzuto R. Protein kinase C beta and prolyl isomerase 1 regulate mitochondrial effects of the life-span determinant p66Shc. Science 2007;315:659–663

    PubMed  CAS  Google Scholar 

  198. Obreztchikova M, Elouardighi H, Ho M, Wilson BA, Gertsberg Z, Steinbeg SF. Distinct signaling functions for SHC isoforms in the heart. J Biol Chem 2006;281:20197–20204

    PubMed  CAS  Google Scholar 

  199. Lee CK, Allison DB, Brand J, Weindruch R, Prolla TA. Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts. Proc Natl Acad Sci USA 2002;99:14988–14993

    PubMed  CAS  Google Scholar 

  200. Rohrbach S, Gruenler S, Teschner M, Holtz J. The thioredoxin system in aging muscle: key role of mitochondrial thioredoxin reductase in the protective effects of caloric restriction? Am J Physiol Regul Integr Comp Physiol 2006;291:R927–R935

    PubMed  CAS  Google Scholar 

  201. Kwak HB, Song W, Lawler JM. Exercise training attenuates age-induced elevation in Bax/Bcl-2 ratio, apoptosis, and remodeling in the rat heart. FASEB J 2006;20:791–793

    PubMed  CAS  Google Scholar 

  202. Anversa P, Rota M, Urbanek K, Hosoda T, Sonnenblick EH, Leri A, Kajstura J, Bolli R. Myocardial aging – a stem cell problem. Basic Res Cardiol 2005;100:482–493

    PubMed  CAS  Google Scholar 

  203. Nadal-Ginard B, Kajstura J, Leri A, Anversa P. Myocyte death, growth, and regeneration in cardiac hypertrophy and failure. Circ Res 2003;92:139–150

    PubMed  CAS  Google Scholar 

  204. Urbanek K, Quaini F, Tasca G, Torella D, Castaldo C, Nadal-Ginard B, Leri A, Kajstura J, Quaini E, Anversa P. Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy. Proc Natl Acad Sci USA 2003;100:10440–10445

    PubMed  CAS  Google Scholar 

  205. Kajstura J, Leri A, Finato N, Di Loreto C, Beltrami CA, Anversa P. Myocyte proliferation in end-stage cardiac failure in humans. Proc Natl Acad Sci USA 1998;95:8801–8805

    PubMed  CAS  Google Scholar 

  206. Beltrami AP, Urbanek K, Kajstura J, Yan SM, Finato N, Bussani R, Nadal-Ginard B, Silvestri F, Leri A, Beltrami CA, Anversa P. Evidence that human cardiac myocytes divide after myocardial infarction. N Engl J Med 2001;344:1750–1757

    PubMed  CAS  Google Scholar 

  207. 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, Anversa P. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 2003;114:763–776

    PubMed  CAS  Google Scholar 

  208. Messina E, De Angelis L, Frati G, Morrone S, Chimenti S, Fiordaliso F, Salio M, Battaglia M, Latronico MV, Coletta M, Vivarelli E, Frati L, Cossu G, Giacomello A. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res 2004;95:911–921

    PubMed  CAS  Google Scholar 

  209. Urbanek K, Cesselli D, Rota M, Nascimbene A, De Angelis A, Hosoda T, Bearzi C, Boni A, Bolli R, Kajstura J, Anversa P, Leri A. Stem cell niches in the adult mouse heart. Proc Natl Acad Sci USA 2006;103:9226–9231

    PubMed  CAS  Google Scholar 

  210. Behfar A, Zingman LV, Hodgson DM, Rauzier JM, Kane GC, Terzic A, Puceat M. Stem cell differentiation requires a paracrine pathway in the heart. FASEB J 2002;16:1558–1566

    PubMed  Google Scholar 

  211. Kofidis T, de Bruin JL, Yamane T, Tanaka M, Lebl DR, Swijnenburg RJ, Weissman IL, Robbins RC. Stimulation of paracrine pathways with growth factors enhances embryonic stem cell engraftment and host-specific differentiation in the heart after ischemic myocardial injury. Circulation 2005;111:2486–2493

    PubMed  CAS  Google Scholar 

  212. Vandervelde S, van Luyn MJ, Tio RA, Harmsen MC. Signaling factors in stem cell-mediated repair of infarcted myocardium. J Mol Cell Cardiol 2005;39:363–376

    PubMed  CAS  Google Scholar 

  213. Min JY, Chen Y, Malek S, Meissner A, Xiang M, Ke Q, Feng X, Nakayama M, Kaplan E, Morgan JP. Stem cell therapy in the aging hearts of Fisher 344 rats: synergistic effects on myogenesis and angiogenesis. J Thorac Cardiovasc Surg 2005;130:547–553

    PubMed  Google Scholar 

  214. Pallante BA, Duignan I, Okin D, Chin A, Bressan MC, Mikawa T, Edelberg JM. Bone marrow Oct3/4+ cells differentiate into cardiac myocytes via age-dependent paracrine mechanisms. Circ Res 2007;100(1):e1–11

    Google Scholar 

  215. Lehrke S, Mazhari R, Durand DJ, Zheng M, Bedja D, Zimmet JM, Schuleri KH, Chi AS, Gabrielson KL, Hare JM. Aging impairs the beneficial effect of granulocyte colony-stimulating factor and stem cell factor on post-myocardial infarction remodeling. Circ Res 2006;99:553–560

    PubMed  CAS  Google Scholar 

  216. Cai D, Xaymardan M, Holm JM, Zheng J, Kizer JR, Edelberg JM. Age-associated impairment in TNF-alpha cardioprotection from myocardial infarction. Am J Physiol Heart Circ Physiol 2003;285:H463–H469

    PubMed  CAS  Google Scholar 

  217. van Vliet P, Sluijter JP, Doevendans PA, Goumans MJ. Isolation and expansion of resident cardiac progenitor cells. Expert Rev Cardiovasc Ther 2007;5:33–43

    PubMed  Google Scholar 

  218. Urbanek K, Rota M, Cascapera S, Bearzi C, Nascimbene A, De Angelis A, Hosoda T, Chimenti S, Baker M, Limana F, Nurzynska D, Torella D, Rotatori F, Rastaldo R, Musso E, Quaini F, Leri A, Kajstura J, Anversa P. Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival. Circ Res 2005;97:663–673

    PubMed  CAS  Google Scholar 

  219. Torella D, Ellison GM, Mendez-Ferrer S, Ibanez B, Nadal-Ginard B. Resident human cardiac stem cells: role in cardiac cellular homeostasis and potential for myocardial regeneration. Nat Clin Pract Cardiovasc Med 2006;3:S8–S13

    PubMed  CAS  Google Scholar 

  220. Torella D, Ellison GM, Karakikes I, Nadal-Ginard B. Growth-factor-mediated cardiac stem cell activation in myocardial regeneration. Nat Clin Pract Cardiovasc Med 2007;4:S46–S51

    PubMed  Google Scholar 

  221. Ellison GM. The pig heart harbors cardiac stem-progenitor cells which respond to growth factor stimulation regenerating the infarcted myocardium [abstract]. Eur Heart J 2006;27:546

    Google Scholar 

  222. Ballard VL, Edelberg JM. Stem cells and the regeneration of the aging cardiovascular system. Circ Res 2007;100:1116–1127

    PubMed  CAS  Google Scholar 

  223. Scheubel RJ, Zorn H, Silber RE, Kuss O, Morawietz H, Holtz J, Simm A. Age-dependent depression in circulating endothelial progenitor cells in patients undergoing coronary artery bypass grafting. J Am Coll Cardiol 2003;42:2073–2080

    PubMed  Google Scholar 

  224. Heiss C, Keymel S, Niesler U, Ziemann J, Kelm M, Kalka C. Impaired progenitor cell activity in age-related endothelial dysfunction. J Am Coll Cardiol 2005;45:1441–1448

    PubMed  CAS  Google Scholar 

  225. Tao J, Wang Y, Yang Z, Tu C, Xu MG, Wang JM. Circulating endothelial progenitor cell deficiency contributes to impaired arterial elasticity in persons of advancing age. J Hum Hypertens 2006;20:490–495

    PubMed  CAS  Google Scholar 

  226. Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA, Finkel T. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 2003;348:593–600

    PubMed  Google Scholar 

  227. Fadini GP, Sartore S, Albiero M, Baesso I, Murphy E, Menegolo M, Grego F, Vigili de Kreutzenberg S, Tiengo A, Agostini C, Avogaro A. Number and function of endothelial progenitor cells as a marker of severity for diabetic vasculopathy. Arterioscler Thromb Vasc Biol 2006;26:2140–2146

    Google Scholar 

  228. Fadini GP, Coracina A, Baesso I, Agostini C, Tiengo A, Avogaro A, de Kreutzenberg SV. Peripheral blood CD34+KDR+ endothelial progenitor cells are determinants of subclinical atherosclerosis in a middle-aged general population. Stroke 2006;37:2277–2282

    Google Scholar 

  229. Rauscher FM, Goldschmidt-Clermont PJ, Davis BH, Wang T, Gregg D, Ramaswami P, Pippen AM, Annex BH, Dong C, Taylor DA. Aging, progenitor cell exhaustion, and atherosclerosis. Circulation 2003;108:457–463

    PubMed  Google Scholar 

  230. Imanishi T, Hano T, Nishio I. Estrogen reduces endothelial progenitor cell senescence through augmentation of telomerase activity. J Hypertens 2005;23:1699–1706

    PubMed  CAS  Google Scholar 

  231. Strehlow K, Werner N, Berweiler J, Link A, Dirnagl U, Priller J, Laufs K, Ghaeni L, Milosevic M, Bohm M, Nickenig G. Estrogen increases bone marrow-derived endothelial progenitor cell production and diminishes neointima formation. Circulation 2003;107:3059–3065

    PubMed  CAS  Google Scholar 

  232. Bernardini D, Ballabio E, Mariotti M, Maier JA. Differential expression of EDF-1 and endothelial nitric oxide synthase by proliferating, quiescent and senescent microvascular endothelial cells. Biochim Biophys Acta 2005;1745:265–272

    PubMed  CAS  Google Scholar 

  233. Papapetropoulos A, Garcia-Cardena G, Madri JA, Sessa WC. Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells. J Clin Invest 1997;100:3131–3139

    PubMed  CAS  Google Scholar 

  234. Lantin-Hermoso RL, Rosenfeld CR, Yuhanna IS, German Z, Chen Z, Shaul PW. Estrogen acutely stimulates nitric oxide synthase activity in fetal pulmonary artery endothelium. Am J Physiol 1997;273:L119–L126

    PubMed  CAS  Google Scholar 

  235. George J, Afek A, Abashidze A, Shmilovich H, Deutsch V, Kopolovich J, Miller H, Keren G. Transfer of endothelial progenitor and bone marrow cells influences atherosclerotic plaque size and composition in apolipoprotein E knockout mice. Arterioscler Thromb Vasc Biol 2005;25:2636–2641

    PubMed  CAS  Google Scholar 

  236. Ballard VL, Edelberg JM. Harnessing hormonal signaling for cardioprotection. Sci Aging Knowledge Environ 2005;2005:re6

    PubMed  Google Scholar 

  237. Thum T, Hoeber S, Froese S, Klink I, Stichtenoth DO, Galuppo P, Jakob M, Tsikas D, Anker SD, Poole-Wilson PA, Borlak J, Ertl G, Bauersachs J. Age-dependent impairment of endothelial progenitor cells is corrected by growth-hormone-mediated increase of insulin-like growth-factor-1. Circ Res 2007;100:434–443

    PubMed  CAS  Google Scholar 

  238. Navarro A, Boveris A. The mitochondrial energy transduction system and the aging process. Am J Physiol Cell Physiol 2007;292:C670–C686

    PubMed  CAS  Google Scholar 

  239. Hunt ND, Hyun DH, Allard JS, Minor RK, Mattson MP, Ingram DK, de Cabo R. Bioenergetics of aging and calorie restriction. Ageing Res Rev 2006;5:125–143

    Google Scholar 

  240. Pepe S. Effect of dietary polyunsaturated fatty acids on age-related changes in cardiac mitochondrial membranes. Exp Gerontol 2005;40:751–758

    PubMed  Google Scholar 

  241. Hagen TM, Moreau R, Suh JH, Visioli F. Mitochondrial decay in the aging rat heart: evidence for improvement by dietary supplementation with acetyl-L-carnitine and/or lipoic acid. Ann NY Acad Sci 2002;959:491–507

    PubMed  CAS  Google Scholar 

  242. Rodriguez MI, Carretero M, Escames G, Lopez LC, Maldonado MD, Tan DX, Reiter RJ, Acuna-Castroviejo D. Chronic melatonin treatment prevents age-dependent cardiac mitochondrial dysfunction in senescence-accelerated mice. Free Radic Res 2007;41:15–24

    PubMed  CAS  Google Scholar 

  243. Kumaran S, Subathra M, Balu M, Panneerselvam C. Supplementation of L-carnitine improves mitochondrial enzymes in heart and skeletal muscle of aged rats. Exp Aging Res 2005;31:55–67

    PubMed  CAS  Google Scholar 

  244. Zhao K, Zhao GM, Wu D, Soong Y, Birk AV, Schiller PW, Szeto HH. Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. J Biol Chem 2004;279:34682–34690

    PubMed  CAS  Google Scholar 

  245. Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, Wallace DC, Rabinovitch PS. Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 2005;308:1909–1911

    PubMed  CAS  Google Scholar 

  246. Ren J, Li Q, Wu S, Li SY, Babcock SA. Cardiac overexpression of antioxidant catalase attenuates aging-induced cardiomyocyte relaxation dysfunction. Mech Ageing Dev 2007;128:276–285

    PubMed  CAS  Google Scholar 

  247. Wu S, Li Q, Du M, Li SY, Ren J. Cardiac-specific overexpression of catalase prolongs life span and attenuates ageing-induced cardiomyocyte contractile dysfunction and protein damage. Clin Exp Pharmacol Physiol 2007;34:81–87

    PubMed  CAS  Google Scholar 

  248. Communal C, Huq F, Lebeche D, Mestel C, Gwathmey JK, Hajjar RJ. Decreased efficiency of adenovirus-mediated gene transfer in aging cardiomyocytes. Circulation 2003;107:1170–1175

    PubMed  Google Scholar 

  249. Terman A, Brunk UT. Autophagy in cardiac myocyte homeostasis, aging, and pathology. Cardiovasc Res 2005;68:355–365

    PubMed  CAS  Google Scholar 

  250. Bergamini E. Autophagy: a cell repair mechanism that retards ageing and age-associated diseases and can be intensified pharmacologically. Mol Aspects Med 2006;27:403–410

    PubMed  CAS  Google Scholar 

  251. de Grey AD, Alvarez PJ, Brady RO, Cuervo AM, Jerome WG, McCarty PL, Nixon RA, Rittmann BE, Sparrow JR. Medical bioremediation: prospects for the application of microbial catabolic diversity to aging and several major age-related diseases. Ageing Res Rev 2005;4:315–338

    PubMed  Google Scholar 

  252. de Grey AD. Bioremediation meets biomedicine: therapeutic translation of microbial catabolism to the lysosome. Trends Biotechnol 2002;20:452–455

    PubMed  Google Scholar 

  253. Massey AC, Zhang C, Cuervo AM. Chaperone-mediated autophagy in aging and disease. Curr Top Dev Biol 2006;73:205–235

    PubMed  CAS  Google Scholar 

  254. Bergamini E, Cavallini G, Donati A, Gori Z. The anti-ageing effects of caloric restriction may involve stimulation of macroautophagy and lysosomal degradation, and can be intensified pharmacologically. Biomed Pharmacother 2003;57:203–208

    PubMed  CAS  Google Scholar 

  255. Donati A. The involvement of macroautophagy in aging and anti-aging interventions. Mol Aspects Med 2006;27:455–470

    PubMed  CAS  Google Scholar 

  256. Cavallini G, Donati A, Taddei M, Bergamini E. Evidence for selective mitochondrial autophagy and failure in aging. Autophagy 2007;3:26–27

    PubMed  CAS  Google Scholar 

  257. Groban L, Pailes NA, Bennett CD, Carter CS, Chappell MC, Kitzman DW, Sonntag WE. Growth hormone replacement attenuates diastolic dysfunction and cardiac angiotensin II expression in senescent rats. J Gerontol A Biol Sci Med Sci 2006;61:28–35

    PubMed  Google Scholar 

  258. Headrick JP, Willems L, Ashton KJ, Holmgren K, Peart J, Matherne GP. Ischaemic tolerance in aged mouse myocardium: the role of adenosine and effects of A1 adenosine receptor overexpression. J Physiol 2003;549:823–833

    PubMed  CAS  Google Scholar 

  259. 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, Sinclair DA. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006;444:337–342

    Google Scholar 

  260. de la Lastra CA, Villegas I. Resveratrol as an anti-inflammatory and anti-aging agent: mechanisms and clinical implications. Mol Nutr Food Res 2005;49:405–430

    PubMed  Google Scholar 

  261. Das DK, Maulik N. Resveratrol in cardioprotection: a therapeutic promise of alternative medicine. Mol Interv 2006;6:36–47

    PubMed  CAS  Google Scholar 

  262. Susic D, Varagic J, Ahn J, Matavelli L, Frohlich ED. Long-term mineralocorticoid receptor blockade reduces fibrosis and improves cardiac performance and coronary hemodynamics in elderly SHR. Am J Physiol Heart Circ Physiol 2007;292:H175–H179

    PubMed  CAS  Google Scholar 

  263. Saka M, Obata K, Ichihara S, Cheng XW, Kimata H, Noda A, Izawa H, Nagata K, Yokota M. Attenuation of ventricular hypertrophy and fibrosis in rats by pitavastatin: potential role of the RhoA-extracellular signal-regulated kinase-serum response factor signalling pathway. Clin Exp Pharmacol Physiol 2006;33:1164–1171

    PubMed  CAS  Google Scholar 

  264. Kumar A, Meyerrose G, Sood V, Roongsritong C. Diastolic heart failure in the elderly and the potential role of aldosterone antagonists. Drugs Aging 2006;23:299–308

    PubMed  CAS  Google Scholar 

  265. Diaz-Araya G, Borg TK, Lavandero S, Loftis MJ, Carver W. IGF-1 modulation of rat cardiac fibroblast behavior and gene expression is age-dependent. Cell Commun Adhes 2003;10:155–165

    PubMed  CAS  Google Scholar 

  266. Zieman S, Kass D. Advanced glycation end product cross-linking: pathophysiologic role and therapeutic target in cardiovascular disease. Congest Heart Fail 2004;10:144–149

    PubMed  CAS  Google Scholar 

  267. Furber JD. Extracellular glycation crosslinks: prospects for removal. Rejuvenation Res 2006;9:274–278

    PubMed  CAS  Google Scholar 

  268. Bakris GL, Bank AJ, Kass DA, Neutel JM, Preston RA, Oparil S. Advanced glycation end-product cross-link breakers. A novel approach to cardiovascular pathologies related to the aging process. Am J Hypertens 2004;17:23S–30S

    PubMed  CAS  Google Scholar 

  269. Zieman SJ, Melenovsky V, Clattenburg L, Corretti MC, Capriotti A, Gerstenblith G, Kass DA. Advanced glycation endproduct crosslink breaker (alagebrium) improves endothelial function in patients with isolated systolic hypertension. J Hypertens 2007;25:577–583

    PubMed  CAS  Google Scholar 

  270. Monnier VM, Mustata GT, Biemel KL, Reihl O, Lederer MO, Zhenyu D, Sell DR. Cross-linking of the extracellular matrix by the maillard reaction in aging and diabetes: an update on “a puzzle nearing resolution”. Ann NY Acad Sci 2005;1043:533–544

    PubMed  CAS  Google Scholar 

  271. Schmidt U, del Monte F, Miyamoto MI, Matsui T, Gwathmey JK, Rosenzweig A, Hajjar RJ. Restoration of diastolic function in senescent rat hearts through adenoviral gene transfer of sarcoplasmic reticulum Ca(2+)-ATPase. Circulation 2000;101:790–796

    PubMed  CAS  Google Scholar 

  272. Schmidt U, Zhu X, Lebeche D, Huq F, Guerrero JL, Hajjar RJ. In vivo gene transfer of parvalbumin improves diastolic function in aged rat hearts. Cardiovasc Res 2005;66:318–323

    PubMed  CAS  Google Scholar 

  273. Li Q, Wu S, Li SY, Lopez FL, Du M, Kajstura J, Anversa P, Ren J. Cardiac-specific overexpression of insulin-like growth factor 1 attenuates aging-associated cardiac diastolic contractil dysfunction and protein damage. Am J Physiol Heart Circ Physiol 2007;292:H1398–H1403

    PubMed  CAS  Google Scholar 

  274. Guo KK, Ren J. Cardiac overexpression of alcohol dehydrogenase (ADH) alleviates aging-associated cardiomyocyte contractile dysfunction: role of intracellular Ca2+ cycling proteins. Aging Cell 2006;5:259–265

    PubMed  CAS  Google Scholar 

  275. Fang CX, Doser TA, Yang X, Sreejayan N, Ren J. Metallothionein antagonizes aging-induced cardiac contractile dysfunction: role of PTP1B, insulin receptor tyrosine phosphorylation and Akt. Aging Cell 2006;5:177–185

    PubMed  CAS  Google Scholar 

  276. Ames BN, Atamna H, Killilea DW. Mineral and vitamin deficiencies can accelerate the mitochondrial decay of aging. Mol Aspects Med 2005;26:363–378

    PubMed  CAS  Google Scholar 

  277. Courtemanche C, Huang AC, Elson-Schwab I, Kerry N, Ng BY, Ames BN. Folate deficiency and ionizing radiation cause DNA breaks in primary human lymphocytes: a comparison. FASEB J 2004;18:209–211

    PubMed  CAS  Google Scholar 

  278. Ames BN. A role for supplements in optimizing health: the metabolic tune-up. Arch Biochem Biophys 2004;423:227–234

    PubMed  CAS  Google Scholar 

  279. Kornman KS. Interleukin 1 genetics, inflammatory mechanisms, and nutrigenetic opportunities to modulate diseases of aging. Am J Clin Nutr 2006;83:475S–483S

    PubMed  CAS  Google Scholar 

  280. Olaharski AJ, Rine J, Marshall BL, Babiarz J, Zhang L, Verdin E, Smith MT. The flavoring agent dihydrocoumarin reverses epigenetic silencing and inhibits sirtuin deacetylases. PLoS Genet 2005;1:e77

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Marín-García, J., Goldenthal, M.J., Moe, G.W. (2008). Aging and the Frontier Ahead. In: Aging and the Heart. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-74072-0_16

Download citation

  • DOI: https://doi.org/10.1007/978-0-387-74072-0_16

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-387-74071-3

  • Online ISBN: 978-0-387-74072-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics