Skip to main content
Log in

Epigenetic factors in aging and longevity

  • Molecular and Genomic Physiology
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

Epigenetics refers to phenotypic changes caused by mechanisms that are unrelated to changes in the underlying DNA sequence, most notably chromatin remodeling driven by histone modifications, and DNA methylation. Such variation is transmitted by cell division, but generally not passed on through the germ line. An increasing body of evidence supports a role for epigenetic changes in the etiology of aging and its associated disease sequelae. Here, we review the role of epigenetics in aging and longevity with a focus on DNA methylation. Increased understanding of those aging-related processes that are driven by epigenetic mechanisms will allow for the development of novel epigenetic-based diagnostic, preventive, and therapeutic strategies for age-related diseases.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Anway MD, Cupp AS, Uzumcu M, Skinner MK (2005) Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 308:1466–1469

    CAS  PubMed  Google Scholar 

  2. Bahar R, Hartmann CH, Rodriguez KA, Denny AD, Busuttil RA, Dollé ME, Calder RB, Chisholm GB, Pollock BH, Klein CA, Vijg J (2006) Increased cell-to-cell variation in gene expression in ageing mouse heart. Nature 441:1011–1014

    CAS  PubMed  Google Scholar 

  3. Barbot W, Dupressoir A, Lazar V, Heidmann T (2002) Epigenetic regulation of an IAP retrotransposon in the aging mouse: progressive demethylation and de-silencing of the element by its repetitive induction. Nucleic Acids Res 30:2365–2373

    CAS  PubMed  Google Scholar 

  4. 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 (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444:337–342

    CAS  PubMed  Google Scholar 

  5. Baylin SB, Herman JG (2001) Promoter hypermethylation—can this change alone ever designate true tumor suppressor gene function? J Natl Cancer Inst 93:664–665

    CAS  PubMed  Google Scholar 

  6. Baylin SB, Herman JG (2000) DNA hypermethylation in tumorigenesis: epigenetics joins genetics. Trends Genet 16:168–174

    CAS  PubMed  Google Scholar 

  7. Bennett-Baker PE, Wilkowski J, Burke DT (2003) Age-associated activation of epigenetically repressed genes in the mouse. Genetics 165:2055–2062

    CAS  PubMed  Google Scholar 

  8. Bjornsson HT, Sigurdsson MI, Fallin MD, Irizarry RA, Aspelund T, Cui H, Yu W, Rongione MA, Ekstrom TJ, Harris TB, Launer LJ, Eiriksdottir G, Leppert MF, Sapienza C, Gudnason V, Feinberg AP (2008) Intra-individual change over time in DNA methylation with familial clustering. JAMA 299:2877–2883

    CAS  PubMed  Google Scholar 

  9. Boyes J, Bird A (1991) DNA methylation inhibits transcription indirectly via a methyl-CpG binding protein. Cell 64:1123–1134

    CAS  PubMed  Google Scholar 

  10. Buck MJ, Lieb JD (2004) ChIP-chip: considerations for the design, analysis, and application of genome-wide chromatin immunoprecipitation experiments. Genomics 83:349–360

    CAS  PubMed  Google Scholar 

  11. Buiting K, Gross S, Lich C, Gillessen-Kaesbach G, el-Maarri O, Horsthemke B (2003) Epimutations in Prader-Willi and Angelman syndromes: a molecular study of 136 patients with an imprinting defect. Am J Hum Genet 72:571–577

    CAS  PubMed  Google Scholar 

  12. Busuttil R, Bahar R, Vijg J (2007) Genome dynamics and transcriptional deregulation in aging. Neuroscience 145:1341–1347

    CAS  PubMed  Google Scholar 

  13. Campisi J (2000) Cancer, aging and cellular senescence. In Vivo 14:183–188

    CAS  PubMed  Google Scholar 

  14. Campisi J (2005) Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120:513–522

    CAS  PubMed  Google Scholar 

  15. Campisi J, d'Adda di Fagagna F (2007) Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol 8:729–740

    CAS  PubMed  Google Scholar 

  16. Campisi J, Kim SH, Lim CS, Rubio M (2001) Cellular senescence, cancer and aging: the telomere connection. Exp Gerontol 36:1619–1637

    CAS  PubMed  Google Scholar 

  17. Campisi J, Vijg J (2009) Does damage to DNA and other macromolecules play a role in aging? If so, how? J Gerontol A Biol Sci Med Sci 64:175–178

    PubMed  Google Scholar 

  18. Chandler VL, Stam M (2004) Chromatin conversations: mechanisms and implications of paramutation. Nat Rev Genet 5:532–544

    CAS  PubMed  Google Scholar 

  19. Clayton AL, Hazzalin CA, Mahadevan LC (2006) Enhanced histone acetylation and transcription: a dynamic perspective. Mol Cell 23:289–296

    CAS  PubMed  Google Scholar 

  20. Coppe JP, Patil CK, Rodier F, Sun Y, Munoz DP, Goldstein J, Nelson PS, Desprez PY, Campisi J (2008) Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 6:2853–2868

    CAS  PubMed  Google Scholar 

  21. DeBusk FL (1972) The Hutchinson-Gilford progeria syndrome. Report of 4 cases and review of the literature. J Pediatr 80:697–724

    CAS  PubMed  Google Scholar 

  22. Di Micco R, Fumagalli M, Cicalese A, Piccinin S, Gasparini P, Luise C, Schurra C, Garre M, Nuciforo PG, Bensimon A, Maestro R, Pelicci PG, d'Adda di Fagagna F (2006) Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature 444:638–642

    PubMed  Google Scholar 

  23. Dillon N, Festenstein R (2002) Unravelling heterochromatin: competition between positive and negative factors regulates accessibility. Trends Genet 18:252–258

    CAS  PubMed  Google Scholar 

  24. Dolinoy DC, Weidman JR, Waterland RA, Jirtle RL (2006) Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome. Environ Health Perspect 114:567–572

    CAS  PubMed  Google Scholar 

  25. Dollé ME, Giese H, van Steeg H, Vijg J (2000) Mutation accumulation in vivo and the importance of genome stability in aging and cancer. Results Probl Cell Differ 29:165–180

    PubMed  Google Scholar 

  26. Eden A, Gaudet F, Waghmare A, Jaenisch R (2003) Chromosomal instability and tumors promoted by DNA hypomethylation. Science 300:455

    CAS  PubMed  Google Scholar 

  27. Ehrich M, Nelson MR, Stanssens P, Zabeau M, Liloglou T, Xinarianos G, Cantor CR, Field JK, van den Boom D (2005) Quantitative high-throughput analysis of DNA methylation patterns by base-specific cleavage and mass spectrometry. Proc Natl Acad Sci USA 102:15785–15790

    CAS  PubMed  Google Scholar 

  28. Feinberg AP (2008) Epigenetics at the epicenter of modern medicine. JAMA 299:1345–1350

    CAS  PubMed  Google Scholar 

  29. Feinberg AP, Ohlsson R, Henikoff S (2006) The epigenetic progenitor origin of human cancer. Nat Rev Genet 7:21–33

    CAS  PubMed  Google Scholar 

  30. Ferguson-Smith AC, Surani MA (2001) Imprinting and the epigenetic asymmetry between parental genomes. Science 293:1086–1089

    CAS  PubMed  Google Scholar 

  31. Fischle W, Wang Y, Jacobs SA, Kim Y, Allis CD, Khorasanizadeh S (2003) Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains. Genes Dev 17:1870–1881

    CAS  PubMed  Google Scholar 

  32. Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suner D, Cigudosa JC, Urioste M, Benitez J, Boix-Chornet M, Sanchez-Aguilera A, Ling C, Carlsson E, Poulsen P, Vaag A, Stephan Z, Spector TD, Wu YZ, Plass C, Esteller M (2005) Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA 102:10604–10609

    CAS  PubMed  Google Scholar 

  33. Friso S, Choi SW (2002) Gene–nutrient interactions and DNA methylation. J Nutr 132:2382S–2387S

    CAS  PubMed  Google Scholar 

  34. Fu VX, Dobosy JR, Desotelle JA, Almassi N, Ewald JA, Srinivasan R, Berres M, Svaren J, Weindruch R, Jarrard DF (2008) Aging and cancer-related loss of insulin-like growth factor 2 imprinting in the mouse and human prostate. Cancer Res 68:6797–6802

    CAS  PubMed  Google Scholar 

  35. Fuks F, Burgers WA, Godin N, Kasai M, Kouzarides T (2001) Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription. EMBO J 20:2536–2544

    CAS  PubMed  Google Scholar 

  36. Gaudet F, Hodgson JG, Eden A, Jackson-Grusby L, Dausman J, Gray JW, Leonhardt H, Jaenisch R (2003) Induction of tumors in mice by genomic hypomethylation. Science 300:489–492

    CAS  PubMed  Google Scholar 

  37. Giese H, Snyder WK, van Oostrom C, van Steeg H, Dollé ME, Vijg J (2002) Age-related mutation accumulation at a lacZ reporter locus in normal and tumor tissues of Trp53-deficient mice. Mutat Res 514:153–163

    CAS  PubMed  Google Scholar 

  38. Glasspool RM, Teodoridis JM, Brown R (2006) Epigenetics as a mechanism driving polygenic clinical drug resistance. Br J Cancer 94:1087–1092

    CAS  PubMed  Google Scholar 

  39. Gray MD, Jesch SA, Stein GH (1991) 5-Azacytidine-induced demethylation of DNA to senescent level does not block proliferation of human fibroblasts. J Cell Physiol 149:477–484

    CAS  PubMed  Google Scholar 

  40. Grewal SI, Elgin SC (2002) Heterochromatin: new possibilities for the inheritance of structure. Curr Opin Genet Dev 12:178–187

    CAS  PubMed  Google Scholar 

  41. Grewal SI, Klar AJ (1996) Chromosomal inheritance of epigenetic states in fission yeast during mitosis and meiosis. Cell 86:95–101

    CAS  PubMed  Google Scholar 

  42. Guarente L (1999) Diverse and dynamic functions of the Sir silencing complex. Nat Genet 23:281–285

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  44. Harley CB, Futcher AB, Greider CW (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345:458–460

    CAS  PubMed  Google Scholar 

  45. Hayflick L (1965) The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 37:614–636

    CAS  PubMed  Google Scholar 

  46. Hegele RA (2003) Drawing the line in progeria syndromes. Lancet 362:416–417

    PubMed  Google Scholar 

  47. Herbig U, Jobling WA, Chen BP, Chen DJ, Sedivy JM (2004) Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol Cell 14:501–513

    CAS  PubMed  Google Scholar 

  48. Holliday R (1987) The inheritance of epigenetic defects. Science 238:163–170

    CAS  PubMed  Google Scholar 

  49. Issa JP (1999) Aging, DNA methylation and cancer. Crit Rev Oncol Hematol 32:31–43

    CAS  PubMed  Google Scholar 

  50. Itahana K, Campisi J, Dimri GP (2007) Methods to detect biomarkers of cellular senescence: the senescence-associated beta-galactosidase assay. Methods Mol Biol 371:21–31

    CAS  PubMed  Google Scholar 

  51. Jablonka E, Lamb MJ (1989) The inheritance of acquired epigenetic variations. J Theor Biol 139:69–83

    CAS  PubMed  Google Scholar 

  52. Jacob RA (1999) Evidence that diet modification reduces in vivo oxidant damage. Nutr Rev 57:255–258

    CAS  PubMed  Google Scholar 

  53. Jones PA (2002) DNA methylation and cancer. Oncogene 21:5358–5360

    CAS  PubMed  Google Scholar 

  54. Jones PA, Laird PW (1999) Cancer epigenetics comes of age. Nat Genet 21:163–167

    CAS  PubMed  Google Scholar 

  55. Kaeberlein M, McVey M, Guarente L (1999) The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev 13:2570–2580

    CAS  PubMed  Google Scholar 

  56. Kanungo A, Chandi SM (1994) Melanotic neuroectodermal tumor of the epididymis. A case report. Indian J Cancer 31:138–140

    CAS  PubMed  Google Scholar 

  57. Kator K, Cristofalo V, Charpentier R, Cutler RG (1985) Dysdifferentiative nature of aging: passage number dependency of globin gene expression in normal human diploid cells grown in tissue culture. Gerontology 31:355–361

    CAS  PubMed  Google Scholar 

  58. Khulan B, Thompson RF, Ye K, Fazzari MJ, Suzuki M, Stasiek E, Figueroa ME, Glass JL, Chen Q, Montagna C, Hatchwell E, Selzer RR, Richmond TA, Green RD, Melnick A, Greally JM (2006) Comparative isoschizomer profiling of cytosine methylation: the HELP assay. Genome Res 16:1046–1055

    CAS  PubMed  Google Scholar 

  59. Krtolica A, Parrinello S, Lockett S, Desprez PY, Campisi J (2001) Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging. Proc Natl Acad Sci USA 98:12072–12077

    CAS  PubMed  Google Scholar 

  60. Kudlow BA, Kennedy BK, Monnat RJ Jr (2007) Werner and Hutchinson-Gilford progeria syndromes: mechanistic basis of human progeroid diseases. Nat Rev Mol Cell Biol 8:394–404

    CAS  PubMed  Google Scholar 

  61. Laird CD, Pleasant ND, Clark AD, Sneeden JL, Hassan KM, Manley NC, Vary JC Jr, Morgan T, Hansen RS, Stoger R (2004) Hairpin-bisulfite PCR: assessing epigenetic methylation patterns on complementary strands of individual DNA molecules. Proc Natl Acad Sci USA 101:204–209

    CAS  PubMed  Google Scholar 

  62. Lane N, Dean W, Erhardt S, Hajkova P, Surani A, Walter J, Reik W (2003) Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis 35:88–93

    CAS  PubMed  Google Scholar 

  63. Liu B, Wang J, Chan KM, Tjia WM, Deng W, Guan X, Huang JD, Li KM, Chau PY, Chen DJ, Pei D, Pendas AM, Cadinanos J, Lopez-Otin C, Tse HF, Hutchison C, Chen J, Cao Y, Cheah KS, Tryggvason K, Zhou Z (2005) Genomic instability in laminopathy-based premature aging. Nat Med 11:780–785

    CAS  PubMed  Google Scholar 

  64. Lumey LH, Stein AD (1997) In utero exposure to famine and subsequent fertility: The Dutch Famine Birth Cohort Study. Am J Public Health 87:1962–1966

    CAS  PubMed  Google Scholar 

  65. Marks PA, Breslow R (2007) Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. Nat Biotechnol 25:84–90

    CAS  PubMed  Google Scholar 

  66. Martin GM (2005) Epigenetic drift in aging identical twins. Proc Natl Acad Sci USA 102:10413–10414

    CAS  PubMed  Google Scholar 

  67. Martin SL, Hopkins CL, Naumer A, Dolle ME, Vijg J (2001) Mutation frequency and type during ageing in mouse seminiferous tubules. Mech Ageing Dev 122:1321–1331

    CAS  PubMed  Google Scholar 

  68. Menendez L, Benigno BB, McDonald JF (2004) L1 and HERV-W retrotransposons are hypomethylated in human ovarian carcinomas. Mol Cancer 3:12

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  70. Morgan HD, Sutherland HG, Martin DI, Whitelaw E (1999) Epigenetic inheritance at the agouti locus in the mouse. Nat Genet 23:314–318

    CAS  PubMed  Google Scholar 

  71. Morley R (2006) Fetal origins of adult disease. Semin Fetal Neonatal Med 11:73–78

    PubMed  Google Scholar 

  72. Muller HJ, Altenburg E (1930) The frequency of translocations produced by x-rays in drosophila. Genetics 15:283–311

    CAS  PubMed  Google Scholar 

  73. Nan X, Campoy FJ, Bird A (1997) MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin. Cell 88:471–481

    CAS  PubMed  Google Scholar 

  74. Narita M, Nunez S, Heard E, Lin AW, Hearn SA, Spector DL, Hannon GJ, Lowe SW (2003) Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell 113:703–716

    CAS  PubMed  Google Scholar 

  75. Oberdoerffer P, Michan S, McVay M, Mostoslavsky R, Vann J, Park SK, Hartlerode A, Stegmuller J, Hafner A, Loerch P, Wright SM, Mills KD, Bonni A, Yankner BA, Scully R, Prolla TA, Alt FW, Sinclair DA (2008) SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging. Cell 135:907–918

    CAS  PubMed  Google Scholar 

  76. Okamoto I, Otte AP, Allis CD, Reinberg D, Heard E (2004) Epigenetic dynamics of imprinted X inactivation during early mouse development. Science 303:644–649

    CAS  PubMed  Google Scholar 

  77. Okano M, Takebayashi S, Okumura K, Li E (1999) Assignment of cytosine-5 DNA methyltransferases Dnmt3a and Dnmt3b to mouse chromosome bands 12A2–A3 and 2H1 by in situ hybridization. Cytogenet Cell Genet 86:333–334

    CAS  PubMed  Google Scholar 

  78. Ono T, Dean RG, Chattopadhyay SK, Cutler RG (1985) Dysdifferentiative nature of aging: age-dependent expression of MuLV and globin genes in thymus, liver and brain in the AKR mouse strain. Gerontology 31:362–372

    CAS  PubMed  Google Scholar 

  79. Park PJ (2008) Epigenetics meets next-generation sequencing. Epigenetics 3:318–321

    Article  PubMed  Google Scholar 

  80. Pembrey ME, Bygren LO, Kaati G, Edvinsson S, Northstone K, Sjostrom M, Golding J (2006) Sex-specific, male-line transgenerational responses in humans. Eur J Hum Genet 14:159–166

    PubMed  Google Scholar 

  81. Rakyan VK, Chong S, Champ ME, Cuthbert PC, Morgan HD, Luu KV, Whitelaw E (2003) Transgenerational inheritance of epigenetic states at the murine Axin(Fu) allele occurs after maternal and paternal transmission. Proc Natl Acad Sci USA 100:2538–2543

    CAS  PubMed  Google Scholar 

  82. Reik W, Dean W, Walter J (2001) Epigenetic reprogramming in mammalian development. Science 293:1089–1093

    CAS  PubMed  Google Scholar 

  83. Robertson KD (2001) DNA methylation, methyltransferases, and cancer. Oncogene 20:3139–3155

    CAS  PubMed  Google Scholar 

  84. Rodenhiser D, Mann M (2006) Epigenetics and human disease: translating basic biology into clinical applications. CMAJ 174:341–348

    PubMed  Google Scholar 

  85. Rogina B, Helfand SL (2004) Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc Natl Acad Sci USA 101:15998–16003

    CAS  PubMed  Google Scholar 

  86. Romanov GA, Vaniushin BF (1980) Intragenomic specificity of DNA methylation in animals. Qualitative differences in tissues and changes in methylation of repeating sequences during aging, carcinogenesis and hormonal induction. Mol Biol (Mosk) 14:357–368

    CAS  Google Scholar 

  87. Rountree MR, Bachman KE, Baylin SB (2000) DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci. Nat Genet 25:269–277

    CAS  PubMed  Google Scholar 

  88. Santos F, Hendrich B, Reik W, Dean W (2002) Dynamic reprogramming of DNA methylation in the early mouse embryo. Dev Biol 241:172–182

    CAS  PubMed  Google Scholar 

  89. Scaffidi P, Misteli T (2005) Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome. Nat Med 11:440–445

    CAS  PubMed  Google Scholar 

  90. Scaffidi P, Misteli T (2006) Lamin A-dependent nuclear defects in human aging. Science 312:1059–1063

    CAS  PubMed  Google Scholar 

  91. Schmid M, Haaf T, Grunert D (1984) 5-Azacytidine-induced undercondensations in human chromosomes. Hum Genet 67:257–263

    CAS  PubMed  Google Scholar 

  92. Schumacher A, Petronis A (2006) Epigenetics of complex diseases: from general theory to laboratory experiments. Curr Top Microbiol Immunol 310:81–115

    CAS  PubMed  Google Scholar 

  93. Shay JW, Roninson IB (2004) Hallmarks of senescence in carcinogenesis and cancer therapy. Oncogene 23:2919–2933

    CAS  PubMed  Google Scholar 

  94. Shumaker DK, Dechat T, Kohlmaier A, Adam SA, Bozovsky MR, Erdos MR, Eriksson M, Goldman AE, Khuon S, Collins FS, Jenuwein T, Goldman RD (2006) Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging. Proc Natl Acad Sci USA 103:8703–8708

    CAS  PubMed  Google Scholar 

  95. Siegmund KD, Connor CM, Campan M, Long TI, Weisenberger DJ, Biniszkiewicz D, Jaenisch R, Laird PW, Akbarian S (2007) DNA methylation in the human cerebral cortex is dynamically regulated throughout the life span and involves differentiated neurons. PLoS ONE 2:e895

    PubMed  Google Scholar 

  96. Sims RJ 3rd, Reinberg D (2009) Processing the H3K36me3 signature. Nat Genet 41:270–271

    CAS  PubMed  Google Scholar 

  97. Sinclair DA, Guarente L (1997) Extrachromosomal rDNA circles—a cause of aging in yeast. Cell 91:1033–1042

    CAS  PubMed  Google Scholar 

  98. Sommer M, Poliak N, Upadhyay S, Ratovitski E, Nelkin BD, Donehower LA, Sidransky D (2006) DeltaNp63alpha overexpression induces downregulation of Sirt1 and an accelerated aging phenotype in the mouse. Cell Cycle 5:2005–2011

    CAS  PubMed  Google Scholar 

  99. Thompson RF, Suzuki M, Lau KW, Greally JM (2009) A pipeline for the quantitative analysis of CG dinucleotide methylation using mass spectrometry. Bioinformatics Resource Number

  100. Tra J, Kondo T, Lu Q, Kuick R, Hanash S, Richardson B (2002) Infrequent occurrence of age-dependent changes in CpG island methylation as detected by restriction landmark genome scanning. Mech Ageing Dev 123:1487–1503

    CAS  PubMed  Google Scholar 

  101. Vidal DO, Paixao VA, Brait M, Souto EX, Caballero OL, Lopes LF, Vettore AL (2007) Aberrant methylation in pediatric myelodysplastic syndrome. Leuk Res 31:175–181

    CAS  PubMed  Google Scholar 

  102. Vijg J, Dollé ME (2002) Large genome rearrangements as a primary cause of aging. Mech Ageing Dev 123:907–915

    CAS  PubMed  Google Scholar 

  103. Vogelstein B, Kinzler KW (1993) The multistep nature of cancer. Trends Genet 9:138–141

    CAS  PubMed  Google Scholar 

  104. Wang H, Cao R, Xia L, Erdjument-Bromage H, Borchers C, Tempst P, Zhang Y (2001) Purification and functional characterization of a histone H3-lysine 4-specific methyltransferase. Mol Cell 8:1207–1217

    CAS  PubMed  Google Scholar 

  105. Wang SC, Oelze B, Schumacher A (2008) Age-specific epigenetic drift in late-onset Alzheimer's disease. PLoS ONE 3:e2698

    PubMed  Google Scholar 

  106. Wareham KA, Lyon MF, Glenister PH, Williams ED (1987) Age related reactivation of an X-linked gene. Nature 327:725–727

    CAS  PubMed  Google Scholar 

  107. Waterland RA, Lin JR, Smith CA, Jirtle RL (2006) Post-weaning diet affects genomic imprinting at the insulin-like growth factor 2 (Igf2) locus. Hum Mol Genet 15:705–716

    CAS  PubMed  Google Scholar 

  108. Watt F, Molloy PL (1988) Cytosine methylation prevents binding to DNA of a HeLa cell transcription factor required for optimal expression of the adenovirus major late promoter. Genes Dev 2:1136–1143

    CAS  PubMed  Google Scholar 

  109. Weaver IC, Diorio J, Seckl JR, Szyf M, Meaney MJ (2004) Early environmental regulation of hippocampal glucocorticoid receptor gene expression: characterization of intracellular mediators and potential genomic target sites. Ann N Y Acad Sci 1024:182–212

    CAS  PubMed  Google Scholar 

  110. Wiemann SU, Satyanarayana A, Tsahuridu M, Tillmann HL, Zender L, Klempnauer J, Flemming P, Franco S, Blasco MA, Manns MP, Rudolph KL (2002) Hepatocyte telomere shortening and senescence are general markers of human liver cirrhosis. FASEB J 16:935–942

    CAS  PubMed  Google Scholar 

  111. Wilson VL, Smith RA, Ma S, Cutler RG (1987) Genomic 5-methyldeoxycytidine decreases with age. J Biol Chem 262:9948–9951

    CAS  PubMed  Google Scholar 

  112. Wright WE, Shay JW (1992) Telomere positional effects and the regulation of cellular senescence. Trends Genet 8:193–197

    CAS  PubMed  Google Scholar 

  113. Young J, Smith JR (2000) Epigenetic aspects of cellular senescence. Exp Gerontol 35:23–32

    CAS  PubMed  Google Scholar 

  114. Young JI, Smith JR (2001) DNA methyltransferase inhibition in normal human fibroblasts induces a p21-dependent cell cycle withdrawal. J Biol Chem 276:19610–19616

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the SENS Foundation, the National Institute on Aging, and the Ellison Medical Foundation for supporting the research of the authors.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Silvia Gravina or Jan Vijg.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gravina, S., Vijg, J. Epigenetic factors in aging and longevity. Pflugers Arch - Eur J Physiol 459, 247–258 (2010). https://doi.org/10.1007/s00424-009-0730-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-009-0730-7

Keywords

Navigation