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Epigenetics and Ageing

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Abstract

The term epigenetics refers to the heritable alterations not due to changes in DNA sequences, which modulate the individual phenotype by modulating the expression and the activity of genes (Armstrong, Epigenetics, Garland Science, New York, 2013; Pinel et al., BioSocieties 13:276–303, 2018). In fact, DNA methylation and histone modification, that are covalent and non-covalent modifications of DNA and histone proteins, alter DNA accessibility and overall chromatin structure, thereby regulating patterns of gene expression (Huang et al., Epigenomics 6:73–88, 2014; Allis and Jenuwein, Nat Rev Genet 17:487–500, 2016).

More recently, epigenetics has also addressed the role of small non-coding RNAs in influencing gene expression levels (Moazed, Nature 457:413–420, 2009; Goldstein et al., Genome Res 27:462–470, 2017).

As these processes are influenced by environmental factors, epigenetics is often considered as a bridge between genome and environment in the definition of phenotype (Norouzitallab et al., Sci Total Environ 647:1281–1293, 2018). Many evidences have suggested in the last decade that ageing, which is deeply influenced by genetics, environment and their interaction, may be influenced by (and at the same time influence) epigenetics. In this chapter, we review both epigenetic modifications of DNA structure and the role of non-coding RNAs and their relationship with ageing and age-related phenotypes.

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References

  1. Barros SP, Offenbacher S. Epigenetics: connecting environment and genotype to phenotype and disease. J Dent Res. 2009;88:400–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Illingworth RS, Bird AP. CpG islands—‘a rough guide’. FEBS Lett. 2009;583:1713–20.

    Article  CAS  PubMed  Google Scholar 

  3. Kanherkar RR, Bhatia-Dey N, Csoka AB. Epigenetics across the human lifespan. Front Cell Dev Biol. 2014;2:49.

    PubMed  PubMed Central  Google Scholar 

  4. Schübeler D. Function and information content of DNA methylation. Nature. 2015;517:321–6.

    Article  PubMed  CAS  Google Scholar 

  5. Luo G-Z, Blanco MA, Greer EL, He C, Shi Y. DNA N(6)-methyladenine: a new epigenetic mark in eukaryotes? Nat Rev Mol Cell Biol. 2015;16:705–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Wu TP, Wang T, Seetin MG, Lai Y, et al. DNA methylation on N(6)-adenine in mammalian embryonic stem cells. Nature. 2016;532:329–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sánchez-Romero MA, Cota I, Casadesús J. DNA methylation in bacteria: from the methyl group to the methylome. Curr Opin Microbiol. 2015;25:9–16.

    Article  PubMed  CAS  Google Scholar 

  8. Lister R, Pelizzola M, Dowen RH, et al. Human DNA methylomes at base resolution show widespread epigenomic differences. This was the first report of a human methylome at single-base resolution. Nature. 2009;462:315–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Pinney SE. Mammalian non-CpG methylation: stem cells and beyond. Biology. 2014;3(4):739–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Patil V, Ward RL, Hesson LB. The evidence for functional non-CpG methylation in mammalian cells. Epigenetics. 2014;9(6):823–8.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Deaton AM, Bird A. CpG islands and the regulation of transcription. Genes Dev. 2011;25:1010–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Goldberg AD, Allis CD, Bernstein E. Epigenetics: a landscape takes shape. Cell. 2007;128:635–8.

    Article  CAS  PubMed  Google Scholar 

  13. Gardiner-Garden M, Frommer M. CpG islands in vertebrate genomes. J Mol Biol. 1987;196:261–82.

    Article  CAS  PubMed  Google Scholar 

  14. Moore LD, Le T, Fan G. DNA methylation and its basic function. Neuropsychopharmacology. 2013;38:23–38.

    Article  CAS  PubMed  Google Scholar 

  15. Norouzitallab P, Baruah K, Vanrompay D, Bossier P. Can epigenetics translate environmental cues into phenotypes? Sci Total Environ. 2018;647:1281–93.

    Article  PubMed  CAS  Google Scholar 

  16. Saxonov S, Berg P, Brutlag DL. A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc Natl Acad Sci U S A. 2006;103(5):1412–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Larsen F, Gundersen G, Lopez R, Prydz H. CpG islands as gene markers in the human genome. Genomics. 1992;13:1095–107.

    Article  CAS  PubMed  Google Scholar 

  18. Zhu J, He F, Hu S, Yu J. On the nature of human housekeeping genes. Trends Genet. 2008;24:481–4.

    Article  CAS  PubMed  Google Scholar 

  19. Maunakea AK, Nagarajan RP, Bilenky M, Ballinger TJ, et al. Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature. 2010;466:253–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet. 2012;13:484–92.

    Article  CAS  PubMed  Google Scholar 

  21. Okano M, Bell DW, Haber DA, Li E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell. 1999;99:247–57.

    Article  CAS  PubMed  Google Scholar 

  22. Lyko F. The DNA methyltransferase family: a versatile toolkit for epigenetic regulation. Nat Rev Genet. 2018;19:81–92.

    Article  CAS  PubMed  Google Scholar 

  23. Dan J, Chen T. Genetic studies on mammalian DNA methyltransferases. Adv Exp Med Biol. 2016;945:123–50.

    Article  CAS  PubMed  Google Scholar 

  24. Branco MR, Ficz G, Reik W. Uncovering the role of 5-hydroxymethylcytosine in the epigenome. Nat Rev Genet. 2011;13:7–13.

    Article  PubMed  CAS  Google Scholar 

  25. Guo F, Li X, Liang D, Li T, et al. Active and passive demethylation of male and female pronuclear DNA in the mammalian zygote. Cell Stem Cell. 2014;15:447–59.

    Article  CAS  PubMed  Google Scholar 

  26. Saitou M, Kagiwada S, Kurimoto K. Epigenetic reprogramming in mouse pre-implantation development and primordial germ cells. Development. 2012;139:15–31.

    Article  CAS  PubMed  Google Scholar 

  27. Sadakierska-Chudy A, Kostrzewa RM, Filip M. A comprehensive view of the epigenetic landscape part I: DNA methylation, passive and active DNA demethylation pathways and histone variants. Neurotox Res. 2015;27:84–97.

    Article  CAS  PubMed  Google Scholar 

  28. Penn NW, Suwalski R, O'Riley C, Bojanowski K, Yura R. The presence of 5-hydroxymethylcytosine in animal deoxyribonucleic acid. Biochem J. 1972;126:781–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Naveh-Many T, Cedar H. Active gene sequences are undermethylated. Proc Natl Acad Sci U S A. 1981;78(7):4246–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Waechter DE, Baserga R. Effect of methylation on expression of microinjected genes. Proc Natl Acad Sci U S A. 1982;79:1106–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Hotchkiss RD. The quantitative separation of purines, pyrimidines, and nucleosides by paper chromatography. J Biol Chem. 1948;175(1):315–32.

    CAS  PubMed  Google Scholar 

  32. Griffith JS, Mahler HR. DNA ticketing theory of memory. Nature. 1969;223:580–2.

    Article  CAS  PubMed  Google Scholar 

  33. Tahiliani M, Koh KP, Shen Y, Pastor WA, et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009;324:930–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Koh KP, Yabuuchi A, Rao S, et al. Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells. Cell Stem Cell. 2011;8:200–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wu X, Zhang Y. TET-mediated active DNA demethylation: mechanism, function and beyond. Nat Rev Genet. 2017;18:517–34.

    Article  CAS  PubMed  Google Scholar 

  36. Jones PA. Effects of 5-azacytidine and its 2’-deoxyderivative on cell differentiation and DNA methylation. Pharmacol Ther. 1985;28:17–27.

    Article  CAS  PubMed  Google Scholar 

  37. Jones PA. Altering gene expression with 5-azacytidine. Cell. 1985;40:485–6.

    Article  CAS  PubMed  Google Scholar 

  38. Keshet I, Yisraeli J, Cedar H. Effect of regional DNA methylation on gene expression. Proc Natl Acad Sci U S A. 1985;82:2560–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Yisraeli J, Frank D, Razin A, Cedar H. Effect of in vitro DNA methylation on beta-globin gene expression. Proc Natl Acad Sci. 1988;85:4638–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kass SU, Goddard JP, Adams RL. Specific methylation of vector sequences inhibits transcription from the SV40 early promoter. Biochem Soc Trans. 1993;21:9.

    Article  Google Scholar 

  41. Seelan RS, Mukhopadhyay P, Pisano MM, Greene RM. Effects of 5-Aza-2′-deoxycytidine (decitabine) on gene expression. Drug Metab Rev. 2018;50:193–207.

    Article  CAS  PubMed  Google Scholar 

  42. Yan X, Ehnert S, Culmes M, et al. 5-azacytidine improves the osteogenic differentiation potential of aged human adipose-derived mesenchymal stem cells by DNA demethylation. PLoS One. 2014;9:90846.

    Article  CAS  Google Scholar 

  43. Clouaire T, Stancheva I. Methyl-CpG binding proteins: specialized transcriptional repressors or structural components of chromatin? Cell Mol Life Sci. 2008;65:1509–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Sasai N, Defossez PA. Many paths to one goal? The proteins that recognize methylated DNA in eukaryotes. Int J Dev Biol. 2009;53:323–34.

    Article  CAS  PubMed  Google Scholar 

  45. Singal R, Ginder GD. DNA methylation. Blood. 1999;93:4059–70.

    CAS  PubMed  Google Scholar 

  46. Watt F, Molloy PL. Cytosine methylation prevents binding to DNA of a HeLa cell transcription factor required for optimal expression of the adenovirus major late promoter. Genes Dev. 1988;2:1136–43.

    Article  CAS  PubMed  Google Scholar 

  47. Boyes J, Bird A. DNA methylation inhibits transcription indirectly via a methyl-CpG binding protein. Cell. 1991;64:1123–34.

    Article  CAS  PubMed  Google Scholar 

  48. Yin Y, Morgunova E, Jolma A, et al. Impact of cytosine methylation on DNA binding specificities of human transcription factors. Science. 2017;356(6337)

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  49. Huang B, Jiang C, Zhang R. Epigenetics: the language of the cell? Epigenomics. 2014;6:73–88.

    Article  PubMed  CAS  Google Scholar 

  50. Allis CD, Jenuwein T. The molecular hallmarks of epigenetic control. Nat Rev Genet. 2016;17:487–500.

    Article  CAS  PubMed  Google Scholar 

  51. Bellizzi D, D’aquila P, Scafone T, Giordano M, Riso V, Riccio A, Passarino G. The control region of mitochondrial DNA shows an unusual CpG and non-CpG methylation pattern. DNA Res. 2013;20:537–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ghosh S, Sengupta S, Scaria V. Comparative analysis of human mitochondrial methylomes shows distinct patterns of epigenetic regulation in mitochondria. Mitochondrion. 2014;18:58–62.

    Article  CAS  PubMed  Google Scholar 

  53. Iacobazzi V, Castegna A, Infantino V, Andria G. Mitochondrial DNA methylation as a next-generation biomarker and diagnostic tool. Mol Genet Metab. 2013;110:25–34.

    Article  CAS  PubMed  Google Scholar 

  54. Shock LS, Thakkar PV, Peterson EJ, et al. DNA TSM methyltransferase 1, cytosine methylation, and cytosine hydroxymethylation in mammalian mitochondria. Proc Natl Acad Sci U S A. 2011;108(9):3630–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Rebelo AP, Williams S, Moraes CT. In vivo methylation of mtDNA reveals the dynamics of protein-mtDNA interactions. Nucleic Acids Res. 2009;37:6701–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Cutter AR, Hayes JJ. A brief review of nucleosome structure. FEBS Lett. 2015;589(20 Pt A):2914–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Margueron R, Reinberg D. Chromatin structure and the inheritance of epigenetic information. Nat Rev Genet. 2010;11:285–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Quina AS, Buschbeck M, Di Croce L. Chromatin structure and epigenetics. Biochem Pharmacol. 2006;72:1563–9.

    Article  CAS  PubMed  Google Scholar 

  59. Woodcock CL, Ghosh RP. Chromatin higher-order structure and dynamics. Cold Spring Harbor Perspect Biol. 2010;2:596.

    Article  CAS  Google Scholar 

  60. Fazary AE, Ju YH, Abd-Rabboh HSM. How does chromatin package DNA within nucleus and regulate gene expression? Int J Biol Macromol. 2017;101:862–81.

    Article  CAS  PubMed  Google Scholar 

  61. Swygert SG, Peterson CL. Chromatin dynamics: interplay between remodeling enzymes and histone modifications. Biochim Biophys Acta. 2014;1839:728–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res. 2011;21:381–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Lawrence M, Daujat S, Schneider R. Lateral thinking: how histone modifications regulate gene expression. Trends Genet. 2016;32:42–56.

    Article  CAS  PubMed  Google Scholar 

  64. Zhang T, Cooper S, Brockdorff N. The interplay of histone modifications—writers that read. EMBO Rep. 2015;16:1467–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Wang R, Xin M, Li Y, Zhang P, Zhang M. The functions of histone modification enzymes in cancer. Curr Protein Pept Sci. 2016;17:438–45.

    Article  CAS  PubMed  Google Scholar 

  66. Kouzarides T. Chromatin modifications and their function. Cell. 2007;128(4):693–705.

    Article  CAS  PubMed  Google Scholar 

  67. Tessarz P, Kouzarides T. Histone core modifications regulating nucleosome structure and dynamics. Nat Rev Mol Cell Biol. 2014;15:703–8.

    Article  CAS  PubMed  Google Scholar 

  68. Dimitrova E, Turberfield AH, Klose RJ. Histone demethylases in chromatin biology and beyond. EMBO Rep. 2015;16:1620–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Gelato KA, Fischle W. Role of histone modifications in defining chromatin structure and function. Biol Chem. 2008;389:353–63.

    Article  CAS  PubMed  Google Scholar 

  70. Kiefer CM, Hou C, Little JA, Dean A. Epigenetics of beta-globin gene regulation. Mutat Res. 2008;647:68–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Bártová E, Krejcí J, Harnicarová A, Galiová G, Kozubek S. Histone modifications and nuclear architecture a review. J Histochem Cytochem. 2008;56(8):711–21.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Maleszewska M, Mawer JSP, Tessarz P. Histone modifications in ageing and lifespan regulation. Curr Mol Biol Rep. 2016;2(1):26–35.

    Article  Google Scholar 

  73. Marmorstein R, Zhou MM. Writers and readers of histone acetylation: structure, mechanism, and inhibition. Cold Spring Harb Perspect Biol. 2014;6:18762.

    Article  CAS  Google Scholar 

  74. Seto E, Yoshida M. Erasers of histone acetylation: the histone deacetylase enzymes. Cold Spring Harb Perspect Biol. 2014;6:18713.

    Article  CAS  Google Scholar 

  75. Voss AK, Thomas T. Histone lysine and genomic targets of histone acetyltransferases in mammals. Bioessays. 2018;40(10):e1800078.

    Article  PubMed  CAS  Google Scholar 

  76. Wapenaar H, Dekker FJ. Histone acetyltransferases: challenges in targeting bi-substrate enzymes. Clin Epigenet. 2016;8:59.

    Article  CAS  Google Scholar 

  77. Kirkland JG, Raab JR, Kamakaka RT. TFIIIC bound DNA elements in nuclear organization and insulation. Biochim Biophys Acta Gene Regul Mech. 2013;1829:418–24.

    Article  CAS  Google Scholar 

  78. Marmorstein R, Roth SY. Histone acetyltransferases: function, structure, and catalysis. Curr Opin Genet Dev. 2001;11:155–61.

    Article  CAS  PubMed  Google Scholar 

  79. Greer EL, Shi Y. Histone methylation: a dynamic mark in health, disease and inheritance. Nat Rev Genet. 2012;13:343–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Smith BC, Denu JM. Chemical mechanisms of histone lysine and arginine modifications. Biochim Biophys Acta. 2009;1789:45–57.

    Article  CAS  PubMed  Google Scholar 

  81. Richon VM, Johnston D, Sneeringer CJ, et al. Chemogenetic analysis of human protein methyltransferases. Chem Biol Drug Des. 2011;78:199–210.

    Article  CAS  PubMed  Google Scholar 

  82. Jahan S, Davie JR. Protein arginine methyltransferases (PRMTs): role in chromatin organization. Adv Biol Regul. 2015;57:173–84.

    Article  CAS  PubMed  Google Scholar 

  83. Kimura H. Histone modifications for human epigenome analysis. J Hum Genet. 2013;58:439–45.

    Article  CAS  PubMed  Google Scholar 

  84. Hino S, Kohrogi K, Nakao M. Histone demethylase LSD1 controls the phenotypic plasticity of cancer cells. Cancer Sci. 2016;107:1187–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Shi Y, Lan F, Matson C, Mulligan P. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. J Chem Soc Faraday Trans. 1994;90:533–9.

    Article  Google Scholar 

  86. Anand R, Marmorstein R. Structure and mechanism of lysine-specific demethylase enzymes. J Biol Chem. 2007;282:35425–9.

    Article  CAS  PubMed  Google Scholar 

  87. Nan X, Ng HH, Johnson CA, Laherty CD, et al. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature. 1998;393:386–9.

    Article  CAS  PubMed  Google Scholar 

  88. Kondo Y. Epigenetic cross-talk between DNA methylation and histone modifications in human cancers. Yonsei Med J. 2009;50:455–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Wang J, Hevi S, Kurash JK, Lei H, Gay F, et al. The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation. Nat Genet. 2009;41:125–9.

    Article  CAS  PubMed  Google Scholar 

  90. Rose NR, Klose RJ. Understanding the relationship between DNA methylation and histone lysine methylation. Biochim Biophys Acta. 2014;1839:1362–72.

    Article  CAS  PubMed  Google Scholar 

  91. Du J, Johnson LM, Jacobsen SE, Patel DJ. DNA methylation pathways and their crosstalk with histone methylation. Nat Rev Mol Cell Biol. 2015;16:519–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Fiannaca A, La Rosa M, La Paglia L, Rizzo R, Urso A. NRC: non-coding RNA classifier based on structural features. BioData Min. 2017;10:27.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843–54.

    Article  CAS  PubMed  Google Scholar 

  94. Lee H, Han S, Kwon CS, Lee D. Biogenesis and regulation of the let-7 miRNAs and their functional implications. Protein Cell. 2016;7:100–13.

    Article  CAS  PubMed  Google Scholar 

  95. Sheng P, Fields C, Aadland K, Wei T, Kolaczkowski O, Gu T, et al. Dicer cleaves 5′-extended microRNA precursors originating from RNA polymerase II transcription start sites. Nucleic Acids Res. 2018;46:5737–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Young-Kook K, Boseon K, Narry Kim V. Re-evaluation of the roles of DROSHA, Exportin 5, and DICER in microRNA biogenesis. Proc Natl Acad Sci U S A. 2016;113(13):E1881–9.

    Article  CAS  Google Scholar 

  97. Zhang F, Wang D. The pattern of microRNA binding site distribution. Genes. 2017;8:296.

    Article  CAS  PubMed Central  Google Scholar 

  98. Moretti F, Thermann R, Hentze MW. Mechanism of translational regulation by miR-2 from sites in the 5′ untranslated region or the open reading frame. RNA. 2010;16:2493–502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Denzler R, McGeary SE, Title AC, Agarwal V, Bartel DP, Stoffel M. Impact of MicroRNA levels, target-site complementarity, and cooperativity on competing endogenous RNA-regulated gene expression. Mol Cell. 2016;64:565–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Webster MW, Stowell JAW, Tang TTL, Passmore LA. Analysis of mRNA deadenylation by multi-protein complexes. Methods. 2017;126:95–104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Sohel MH. Extracellular/circulating microRNAs: release mechanisms, functions and challenges. Achievem Life Sci. 2016;10(2):175–86.

    Article  Google Scholar 

  102. Jung HJ, Suh Y. Circulating miRNAs in ageing and ageing-related diseases. J Genet Genomics. 2014;41:465–72.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Jose AM. Movement of regulatory RNA between animal cells. Genesis. 2015;53:395–416.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Hayashi T, Hoffman MP. Exosomal microRNA communication between tissues during organogenesis. RNA Biol. 2017;14:1683–9.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Bayraktar R, Van Roosbroeck K, Calin GA. Cell-to-cell communication: microRNAs as hormones. Mol Oncol. 2017;11:1673–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Johnson FB, Sinclair DA, Guarente L. Molecular biology of aging. Cell. 1999;96:291–302.

    Article  CAS  PubMed  Google Scholar 

  107. Kirkwood TBL. Understanding the odd science of aging. Cell. 2005;120:437–47.

    Article  CAS  PubMed  Google Scholar 

  108. Sebastiani P, Solovieff N, Dewan AT, Walsh KM, et al. Genetic signatures of exceptional longevity in humans. PLoS One. 2012;7:29848.

    Article  CAS  Google Scholar 

  109. Montesanto A, Dato S, Bellizzi D, Rose G, Passarino G. Epidemiological, genetic and epigenetic aspects of the research on healthy ageing and longevity. Immun Ageing. 2012;9:6.

    Article  PubMed  PubMed Central  Google Scholar 

  110. D’Aquila P, Rose G, Bellizzi D, Passarino G. Epigenetics and aging. Maturitas. 2013;74:130–6.

    Article  PubMed  CAS  Google Scholar 

  111. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153:1194–217.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. Pal S, Tyler JK. Epigenetics and aging. Sci Adv. 2016;2:1600584.

    Article  CAS  Google Scholar 

  113. Li Y, Tollefsbol TO. Age-related epigenetic drift and phenotypic plasticity loss: implications in prevention of age-related human diseases. Epigenomics. 2016;8:1637–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Jones MJ, Goodman SJ, Kobor MS. DNA methylation and healthy human aging. Aging Cell. 2015;14:924–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Zampieri M, Ciccarone F, Calabrese R, et al. Reconfiguration of DNA methylation in aging. Mech Ageing Dev. 2015;151:60–70.

    Article  CAS  PubMed  Google Scholar 

  116. Guarasci F, D'Aquila P, Mandalà M, Garasto S, et al. Aging and nutrition induce tissue-specific changes on global DNA methylation status in rats. Mech Ageing Dev. 2018;174:47–54.

    Article  CAS  PubMed  Google Scholar 

  117. Amodio N, D'Aquila P, Passarino G, et al. Epigenetic modifications in multiple myeloma: recent advances on the role of DNA and histone methylation. Expert Opin Ther Targets. 2017;21:91–101.

    Article  CAS  PubMed  Google Scholar 

  118. Martin GM. Epigenetic drift in aging identical twins. Proc Natl Acad Sci U S A. 2005;102:10413–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Lipman T, Tiedje LB. Epigenetic differences arise during the lifetime of monozygotic twins. Am J Matern Nurs. 2006;31:204.

    Google Scholar 

  120. Kaminsky ZA, Tang T, Wang SC, et al. DNA methylation profiles in monozygotic and dizygotic twins. Nat Genet. 2009;41:240–5.

    Article  CAS  PubMed  Google Scholar 

  121. Bell JT, Spector TD. A twin approach to unraveling epigenetics. Trends Genet. 2011;27:116–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Tan Q, Christiansen L, Thomassen M, et al. Twins for epigenetic studies of human aging and development. Ageing Res Rev. 2013;12:182–7.

    Article  PubMed  Google Scholar 

  123. Mendelsohn AR, Larrick JW. Epigenetic drift is a determinant of mammalian lifespan. Rejuvenation Res. 2017;20:430–6.

    Article  PubMed  Google Scholar 

  124. Slieker RC, van Iterson M, Luijk R, et al. Age-related accrual of methylomic variability is linked to fundamental ageing mechanisms. Genome Biol. 2016;7:191.

    Article  CAS  Google Scholar 

  125. Issa JP. Aging and epigenetic drift: a vicious cycle. J Clin Invest. 2014;124:24–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Teschendorff AE, Menon U, Gentry-Maharaj A, et al. Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer. Genome Res. 2010;20:440–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Bacalini MG, D’Aquila P, Marasco E, Nardini C, Montesanto A, Franceschi C, Passarino G, Garagnani P, Bellizzi D. The methylation of nuclear and mitochondrial DNA in ageing phenotypes and longevity. Mech Ageing Dev. 2017;165:156–61.

    Article  CAS  PubMed  Google Scholar 

  128. Rakyan VK, Down TA, Maslau S, Andrew T, et al. Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains. Genome Res. 2010;20:434–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Bell JT, Tsai PC, Yang TP, et al. Epigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population. PLoS Genet. 2012;8(4):e1002629.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Ashapkin VV, Kutueva LI, Vanyushin BF. Aging as an epigenetic phenomenon. Curr Genomics. 2017;18:385–407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Zhang Z, Deng C, Lu Q, Richardson B. Age-dependent DNA methylation changes in the ITGAL (CD11a) promoter. Mech Ageing Dev. 2002;123:1257–68.

    Article  CAS  PubMed  Google Scholar 

  132. Vijg J, Dollé ME. Genome instability: cancer or aging? Mech Ageing Dev. 2007;128:466–8.

    Article  PubMed  PubMed Central  Google Scholar 

  133. Bollati V, Schwartz J, Wright R, et al. Decline in genomic DNA methylation through aging in a cohort of elderly subjects. Mech Ageing Dev. 2009;130:234–9.

    Article  CAS  PubMed  Google Scholar 

  134. Jintaridth P, Mutirangura A. Distinctive patterns of age-dependent hypomethylation in interspersed repetitive sequences. Physiol Genomics. 2010;41:194–200.

    Article  CAS  PubMed  Google Scholar 

  135. Wei L, Liu B, Tuo J, Shen D, et al. Hypomethylation of the IL17RC promoter associates with age-related macular degeneration. Cell Rep. 2012;2(5):1151–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Heyn H, Li N, Ferreira HJ, et al. Distinct DNA methylomes of newborns and centenarians. Proc Natl Acad Sci. 2012;109:10522–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Bellizzi D, D’aquila P, Giordano M, Montesanto A, Passarino G. Global DNA methylation levels are modulated by mitochondrial DNA variants. Epigenomics. 2012;4:17–27.

    Article  CAS  PubMed  Google Scholar 

  138. Bellizzi D, D'Aquila P, Montesanto A, Corsonello A, et al. Global DNA methylation in old subjects is correlated with frailty. Age. 2012;34:169–79.

    Article  CAS  PubMed  Google Scholar 

  139. D’Aquila P, Bellizzi D, Passarino G. rRNA-gene methylation and biological aging. Aging (Albany NY). 2018;10:7–8.

    Article  Google Scholar 

  140. D'Aquila P, Montesanto A, Mandalà M, Garasto S, et al. Methylation of the ribosomal RNA gene promoter is associated with aging and age-related decline. Aging Cell. 2017;16:966–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Bocklandt S, Lin W, Sehl ME, et al. Epigenetic predictor of age. PLoS One. 2011;6:14821.

    Article  CAS  Google Scholar 

  142. Hannum G, Guinney J, Zhao L, Zhang L, Hughes G, Sadda S. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell. 2013;49:359–67.

    Article  CAS  PubMed  Google Scholar 

  143. Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013;14(10):R115.

    Article  PubMed  PubMed Central  Google Scholar 

  144. Marioni RE, Shah S, McRae AF, et al. DNA methylation age of blood predicts all-cause mortality in later life. Genome Biol. 2015;16:25.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  145. Christiansen L, Lenart A, Tan Q, et al. DNA methylation age is associated with mortality in a longitudinal Danish twin study. Aging Cell. 2016;15:149–54.

    Article  CAS  PubMed  Google Scholar 

  146. Perna L, Zhang Y, Mons U, et al. Epigenetic age acceleration predicts cancer, cardiovascular, and all-cause mortality in a German case cohort. Clin Epigenet. 2016;8:64.

    Article  Google Scholar 

  147. Levine ME, Lu AT, Quach A, et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY). 2018;10:573–91.

    Article  Google Scholar 

  148. Obata Y, Furusawa Y, Hase K. Epigenetic modifications of the immune system in health and disease. Immunol Cell Biol. 2015;93:226–32.

    Article  CAS  PubMed  Google Scholar 

  149. Huidobro C, Fernandez AF, Fraga MF. Aging epigenetics: causes and consequences. Mol Aspects Med. 2013;34:765–81.

    Article  CAS  PubMed  Google Scholar 

  150. Lillycrop KA, Burdge GC. Maternal diet as a modifier of offspring epigenetics. J Dev Orig Health Dis. 2015;6:88–95.

    Article  CAS  PubMed  Google Scholar 

  151. Vickers MH. Early life nutrition, epigenetics and programming of later life disease. Nutrients. 2014;6:2165–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Park JH, Kim SH, Lee MS, Kim MS. Epigenetic modification by dietary factors: Implications in metabolic syndrome. Mol Aspects Med. 2017;54:58–70.

    Article  CAS  PubMed  Google Scholar 

  153. Lumey LH, Stein AD, Kahn HS, van der Pal-de Bruin KM, Blauw GJ, Zybert PA, Susser ES. Cohort profile: the Dutch Hunger Winter families study. Int J Epidemiol. 2007;36:1196–204.

    Article  CAS  PubMed  Google Scholar 

  154. Stein AD, Pierik FH, Verrips GHW, Susser ES, Lumey LH. Maternal exposure to the Dutch famine before conception and during pregnancy: quality of life and depressive symptoms in adult offspring. Epidemiology. 2009;20:909–15.

    Article  PubMed  Google Scholar 

  155. D’Aquila P, Montesanto A, Guarasci F, Passarino G, Bellizzi D. Mitochondrial genome and epigenome: two sides of the same coin. Front Biosci (Landmark Ed). 2017;22:888–908.

    Article  Google Scholar 

  156. D'Aquila P, Giordano M, Montesanto A, et al. Age-and gender-related pattern of methylation in the MT-RNR1 gene. Epigenomics. 2015;7:707–16.

    Article  CAS  PubMed  Google Scholar 

  157. Truong TP, Sakata-Yanagimoto M, Yamada M, et al. Influence of age-dependent decrease of DNA hydroxymethylation in human T cells. J Clin Exp Hematopathol. 2015;55:1–6.

    Article  Google Scholar 

  158. Szulwach KE, Li X, Li Y, Song CX, et al. 5-hmC–mediated epigenetic dynamics during postnatal neurodevelopment and aging Keith. Nat Neurosci. 2012;14:1607–16.

    Article  CAS  Google Scholar 

  159. Chouliaras L, van den Hove DL, Kenis G, et al. Age-related increase in levels of 5-hydroxymethylcytosine in mouse hippocampus is prevented by caloric restriction. Curr Alzheimer Res. 2012;9:536–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Dzitoyeva S, Chen H, Manev H. Effect of aging on 5-hydroxymethylcytosine in brain mitochondria. Neurobiol Aging. 2012;33:2881–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Kochmanski J, Marchlewicz EH, Cavalcante RG, Sartor MA, Dolinoy DC. Age-related epigenome-wide DNA methylation and hydroxymethylation in longitudinal mouse blood. Epigenetics. 2018;13(7):779–92.

    Article  PubMed  PubMed Central  Google Scholar 

  162. Feser J, Tyler J. Chromatin structure as a mediator of aging. FEBS Lett. 2011;585:2041–8.

    Article  CAS  PubMed  Google Scholar 

  163. Wang Y, Yuan Q, Xie L. Histone modifications in aging: the underlying mechanisms and implications. Curr Stem Cell Res Ther. 2018;13:125–35.

    CAS  PubMed  Google Scholar 

  164. Dimauro T, David G. Chromatin modifications: the driving force of senescence and aging? Aging (Albany NY). 2009;1:182–90.

    Article  CAS  Google Scholar 

  165. Das C, Tyler JK. Histone exchange and histone modifications during transcription and aging. Biochim Biophys Acta. 2013;1819:332–42.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  166. McCauley BS, Dang W. Histone methylation and aging: lessons learned from model systems. Biochim Biophys Acta. 2014;1839:1454–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Giblin W, Skinner ME, Lombard DB. Sirtuins: guardians of mammalian healthspan. Trends Genet. 2014;30:271–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Poulose N, Raju R. Sirtuin regulation in aging and injury. Biochim Biophys Acta. 2015;1852:2442–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Wątroba M, Dudek I, Skoda M, Stangret A, Rzodkiewicz P, Szukiewicz D. Sirtuins, epigenetics and longevity. Ageing Res Rev. 2017;40:11–9.

    Article  PubMed  CAS  Google Scholar 

  170. Dang W, Steffen KK, Perry R, Dorsey JA, Johnson FB, Shilatifard A, Kaeberlein M, Kennedy BK, Berger SL. Histone H4 lysine-16 acetylation regulates cellular lifespan. Nature. 2009;459(7248):802–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Kanfi Y, Peshti V, Gil R, Naiman S, Nahum L, Levin E, Kronfeld-Schor N, Cohen HY. SIRT6 protects against pathological damage caused by diet-induced obesity. Aging Cell. 2010;9:162–73.

    Article  CAS  PubMed  Google Scholar 

  172. Kanfi Y, Naiman S, Amir G, Peshti V, Zinman G, Nahum L, Bar-Joseph Z, Cohen HY. The sirtuin SIRT6 regulates lifespan in male mice. Nature. 2012;483:218–21.

    Article  CAS  PubMed  Google Scholar 

  173. Mostoslavsky R, Chua KF, Lombard DB, et al. Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell. 2006;124:315–29.

    Article  CAS  PubMed  Google Scholar 

  174. Peleg S, Sananbenesi F, Zovoilis A, et al. Altered histone acetylation is associated with age-dependent memory impairment in mice. Science. 2010;328:753–6.

    Article  CAS  PubMed  Google Scholar 

  175. Herranz D, Cañamero M, Mulero F, Martinez-Pastor B, Fernandez-Capetillo O, Serrano M. Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer syndrome. Nat Commun. 2010;1:3.

    Article  PubMed  CAS  Google Scholar 

  176. Grabowska W, Sikora E, Bielak-Zmijewska A. Sirtuins, a promising target in slowing down the ageing process. Biogerontology. 2017;18:447–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, Howitz KT, Gorospe M, de Cabo R, Sinclair DA. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science. 2004;305:390–2.

    Article  CAS  PubMed  Google Scholar 

  178. Lombard DB, Alt FW, Cheng HL, et al. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol Cell Biol. 2007;27:8807–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Nakagawa H, Nuovo GJ, Zervos EE, Martin EW Jr, Salovaara R, Aaltonen LA, de la Chapelle A. Age-related hypermethylation of the 5' region of MLH1 in normal colonic mucosa is associated with microsatellite-unstable colorectal cancer development. Cancer Res. 2001;61:6991–5.

    CAS  PubMed  Google Scholar 

  180. Pedersen SB, Ølholm J, Paulsen SK, Bennetzen MF, Richelsen B. Low Sirt1 expression, which is upregulated by fasting, in human adipose tissue from obese women. Int J Obes (Lond). 2008;32:1250–5.

    Article  CAS  Google Scholar 

  181. Costa Cdos S, Hammes TO, Rohden F, Margis R, Bortolotto JW, Padoin AV, Mottin CC, Guaragna RM. SIRT1 transcription is decreased in visceral adipose tissue of morbidly obese patients with severe hepatic steatosis. Obes Surg. 2010;20:633–9.

    Article  PubMed  Google Scholar 

  182. Chalkiadaki A, Guarente L. Sirtuins mediate mammalian metabolic responses to nutrient availability. Nat Rev Endocrinol. 2012;8:287–96.

    Article  CAS  PubMed  Google Scholar 

  183. Someya S, Tanokura M, Weindruch R, Prolla TA, Yamasoba T. Effects of caloric restriction on age-related hearing loss in rodents and rhesus monkeys. Curr Aging Sci. 2010;3:20–5.

    Article  PubMed  PubMed Central  Google Scholar 

  184. Motta MC, Divecha N, Lemieux M, Kamel C, Chen D, Gu W, Bultsma Y, McBurney M, Guarente L. Mammalian SIRT1 represses forkhead transcription factors. Cell. 2004;116:551–63.

    Article  CAS  PubMed  Google Scholar 

  185. Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature. 2005;434:113–8.

    Article  CAS  PubMed  Google Scholar 

  186. Gerhart-Hines Z, Rodgers JT, Bare O, Lerin C, Kim SH, Mostoslavsky R, Alt FW, Wu Z, Puigserver P. Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha. EMBO J. 2007;26:1913–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Feige JN, Lagouge M, Canto C, Strehle A, Houten SM, Milne JC, Lambert PD, Mataki C, Elliott PJ, Auwerx J. Specific SIRT1 activation mimics low energy levels and protects against diet-induced metabolic disorders by enhancing fat oxidation. Cell Metab. 2008;8:347–58.

    Article  CAS  PubMed  Google Scholar 

  188. Fulco M, Cen Y, Zhao P, Hoffman EP, McBurney MW, Sauve AA, Sartorelli V. Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt. Dev Cell. 2008;14:661–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Purushotham A, Schug TT, Xu Q, Surapureddi S, Guo X, Li X. Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metab. 2009;9:327–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Hallows WC, Yu W, Denu JM. Regulation of glycolytic enzyme phosphoglycerate mutase-1 by Sirt1 protein-mediated deacetylation. J Biol Chem. 2012;287:3850–8.

    Article  CAS  PubMed  Google Scholar 

  191. Guarente L. Calorie restriction and sirtuins revisited. Genes Dev. 2013;27:2072–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Maugeri A, Barchitta M, Mazzone MG, Giuliano F, Basile G, Agodi A. Resveratrol Modulates SIRT1 and DNMT functions and restores LINE-1 methylation levels in ARPE-19 cells under oxidative stress and inflammation. Int J Mol Sci. 2018;19:2118.

    Article  PubMed Central  CAS  Google Scholar 

  193. De Lencastre A, Pincus Z, Zhou K, Kato M, Lee SS, Slack FJ. MicroRNAs both promote and antagonize longevity in C. elegans. Curr Biol. 2010;20:2159–68.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  194. Isik M, Blackwell TK, Berezikov E. MicroRNA mir-34 provides robustness to environmental stress response via the DAF-16 network in C. elegans. Sci Rep. 2016;6:36766.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Smith-Vikos T, Liu Z, Parsons C, Gorospe M, Ferrucci L, Gill TM, Slack FJ. A serum miRNA profile of human longevity: findings from the Baltimore Longitudinal Study of Ageing (BLSA). Ageing (Albany NY). 2016;8:2971–83.

    CAS  Google Scholar 

  196. Kulshreshtha R, Ferracin M, Wojcik SE, Garzon R, Alder H, Agosto-Perez FJ, Davuluri R, Liu CG, Croce CM, Negrini M, Calin GA, Ivan M. A microRNA signature of hypoxia. Mol Cell Biol. 2007;27:1859–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  197. Rippo MR, Olivieri F, Monsurrò V, Prattichizzo F, Albertini MC, Procopio AD. MitomiRs in human inflamm-ageing: a hypothesis involving miR-181a, miR-34a and miR-146a. Exp Gerontol. 2014;56:154–63.

    Article  CAS  PubMed  Google Scholar 

  198. Rose G, Santoro A, Salvioli S. Mitochondria and mitochondria-induced signalling molecules as longevity determinants. Mech Ageing Dev. 2017;165:115–28.

    Article  CAS  PubMed  Google Scholar 

  199. Olivieri F, Rippo MR, Monsurrò V, Salvioli S, Capri M, Procopio AD, Franceschi C. MicroRNAs linking inflamm-ageing, cellular senescence and cancer. Ageing Res Rev. 2013;12:1056–68.

    Article  CAS  PubMed  Google Scholar 

  200. Baradan R, Hollander JM, Das S. Mitochondrial miRNAs in diabetes: just the tip of the iceberg. Can J Physiol Pharmacol. 2017;95:1156–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Wu S, Kim T-K, Wu X, Scherler K, Baxter D, Wang K, Krasnow RE, Reed T, Dai J. Circulating microRNAs and life expectancy among identical twins. Ann Human Genet. 2016;80:247–56.

    Article  CAS  Google Scholar 

  202. Micó V, Berninches L, Tapia J, Daimiel L. NutrimiRAging: Micromanaging Nutrient Sensing Pathways through Nutrition to Promote Healthy Aging. Int J Mol Sci. 2017;18:915.

    Article  PubMed Central  CAS  Google Scholar 

  203. Kurylowicz A, Owczarz M, Polosak J, Jonas MI, Lisik W, Jonas M, Chmura A, Puzianowska-Kuznicka M. SIRT1 and SIRT7 expression in adipose tissues of obese and normal-weight individuals is regulated by microRNAs but not by methylation status. Int J Obes (Lond). 2016;40:1635–42.

    Article  CAS  Google Scholar 

  204. Ultimo S, Zauli G, Martelli AM, Vitale M, McCubrey JA, Capitani S, Neri LM. Influence of physical exercise on microRNAs in skeletal muscle regeneration, aging and diseases. Oncotarget. 2018;9:17220–37.

    PubMed  PubMed Central  Google Scholar 

  205. Brunet A, Berger SL. Epigenetics of aging and aging-related disease. J Gerontol A Biol Sci Med Sci. 2014;69:S17–20.

    Article  PubMed  PubMed Central  Google Scholar 

  206. Shenouda SK, Alahari SK. MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev. 2009;28:369.

    Article  CAS  PubMed  Google Scholar 

  207. Calin GA, Dumitru CD, Shimizu M, et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2002;99:15524–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Jiang W, Li J, Zhang Z, Wang H, Wang Z. Epigenetic upregulation of alpha-synuclein in the rats exposed to methamphetamine. Eur J Pharmacol. 2014;745:243–8.

    Article  CAS  PubMed  Google Scholar 

  209. Brown DM, Goljanek-Whysall K. microRNAs: modulators of the underlying pathophysiology of sarcopenia? Ageing Res Rev. 2015;24:263–73.

    Article  CAS  PubMed  Google Scholar 

  210. Jingjing F, Xianjuan K, Yi Y, Ning C. MicroRNA-regulated proinflammatory cytokines in sarcopenia. Mediators Inflamm. 2016;2016:1438686.

    Google Scholar 

  211. Shinde S, Mukhopadhyay S, Mohsen G, Khoo SK. Biofluid-based microRNA biomarkers for Parkinson’s disease: an overview and update. AIMS Med Sci. 2015;2:15–25.

    Article  Google Scholar 

  212. Shah P, Cho SK, Thulstrup PW, Bjerrum MJ, Lee PH, Kang JH, Bhang YJ, Yang SW. MicroRNA biomarkers in neurodegenerative diseases and emerging nanosensors technology. J Mov Disorders. 2017;10:18–28.

    Article  Google Scholar 

  213. Schulte C, Zeller T. microRNA-based diagnostics and therapy in cardiovascular disease—summing up the facts. Cardiovasc Diagn Ther. 2015;5:17–36.

    PubMed  PubMed Central  Google Scholar 

  214. Nakasa T, Ishikawa M, Shi M, Shibuya H, Adachi N, Ochi M. Acceleration of muscle regeneration by local injection of muscle-specific microRNAs in rat skeletal muscle injury model. J Cell Mol Med. 2010;14:2495–505.

    Article  CAS  PubMed  Google Scholar 

  215. Duan Q, Yang L, Gong W, Chaugai S, Wang F, Chen C, Wang P, Zou MH, Wang DW. MicroRNA-214 is upregulated in heart failure patients and suppresses XBP1-mediated endothelial cells angiogenesis. J Cell Physiol. 2015;230:1964–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  216. Alavi-Moghaddam M, Chehrazi M, Alipoor SD, Mohammadi M, Baratloo A, Mahjoub MP, Movasaghi M, Garssen J, Adcock IM, Mortaz E. A preliminary study of microRNA-208b after acute myocardial infarction: impact on 6-month survival. Dis Markers. 2018;2018:2410451.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  217. Schulte C, Ji X, Takahashi R, Hiura Y, et al. Plasma miR-208 as a biomarker of myocardial injury. Clin Chem. 2009;55(11):1944–9.

    Article  CAS  Google Scholar 

  218. Reynolds LM, Taylor JR, Ding J, et al. Age-related variations in the methylome associated with gene expression in human monocytes and T cells. Nat Commun. 2014;5:5366.

    Article  PubMed  Google Scholar 

  219. McClay JL, Aberg KA, Clark SL, et al. A methylome-wide study of aging using massively parallel sequencing of the methyl-CpG-enriched genomic fraction from blood in over 700 subjects. Hum Mol Genet. 2014;23(5):1175–85.

    Article  CAS  PubMed  Google Scholar 

  220. Choi EK, Uyeno S, Nishida N, et al. Alterations of c-fos gene methylation in the processes of aging and tumorigenesis in human liver. Mutat Res. 1996;354(1):123–8.

    Article  PubMed  Google Scholar 

  221. Issa JP, Vertino PM, Boehm CD, et al. Switch from monoallelic to biallelic human IGF2 promoter methylation during aging and carcinogenesis. Proc Natl Acad Sci U S A. 1996;93(21):11757–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  222. Ahuja N, Li Q, Mohan AL, Baylin SB, Issa JP. Aging and DNA methylation in colorectal mucosa and cancer. Cancer Res. 1998;58(23):5489–94.

    CAS  PubMed  Google Scholar 

  223. Christensen BC, Houseman EA, Marsit CJ, et al. Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet. 2009;5(8):e1000602.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  224. Vidal AC, Benjamin Neelon SE, Liu Y. Maternal stress, preterm birth, and DNA methylation at imprint regulatory sequences in humans. Genet Epigenet. 2014;6:37–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Nakagawa H, Nuovo GJ, Zervos EE, et al. Age-related hypermethylation of the 5' region of MLH1 in normal colonic mucosa is associated with microsatellite-unstable colorectal cancer development. Cancer Res. 2001;61(19):6991–5.

    CAS  PubMed  Google Scholar 

  226. Matsubayashi H, Sato N, Brune K, et al. Age- and disease-related methylation of multiple genes in nonneoplastic duodenum and in duodenal juice. Clin Cancer Res. 2005;11(2 Pt 1):573–83.

    CAS  PubMed  Google Scholar 

  227. Silva PN, Gigek CO, Leal MF, et al. Promoter methylation analysis of SIRT3, SMARCA5, HTERT and CDH1 genes in aging and Alzheimer’s disease. J Alzheimers Dis. 2008;13(2):173–6.

    Article  CAS  PubMed  Google Scholar 

  228. Madrigano J, Baccarelli A, Mittleman MA, et al. Aging and epigenetics: longitudinal changes in gene-specific DNA methylation. Epigenetics. 2012;7(1):63–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. Rönn T, Poulsen P, Hansson O, et al. Age influences DNA methylation and gene expression of COX7A1 in human skeletal muscle. Diabetologia. 2008;51(7):1159–68.

    Article  PubMed  CAS  Google Scholar 

  230. Gaudet MM, Campan M, Figueroa JD, et al. DNA hypermethylation of ESR1 and PGR in breast cancer: pathologic and epidemiologic associations. Cancer Epidemiol Biomarkers Prev. 2009;18(11):3036–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  231. Fujii H, Biel MA, Zhou W, et al. Methylation of the HIC-1 candidate tumor suppressor gene in human breast cancer. Oncogene. 1998;16(16):2159–64.

    Article  CAS  PubMed  Google Scholar 

  232. Cody DT, Huang Y, Darby CJ, et al. Differential DNA methylation of the p16 INK4A/CDKN2A promoter in human oral cancer cells and normal human oral keratinocytes. Oral Oncol. 1999;35(5):516–22.

    Article  CAS  PubMed  Google Scholar 

  233. Dammann R, Li C, Yoon JH, et al. Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3. Nat Genet. 2000;25(3):315–9.

    Article  CAS  PubMed  Google Scholar 

  234. Virmani AK, Rathi A, Sathyanarayana UG, et al. Aberrant methylation of the adenomatous polyposis coli (APC) gene promoter 1A in breast and lung carcinomas. Clin Cancer Res. 2001;7(7):1998–2004.

    CAS  PubMed  Google Scholar 

  235. Waki T, Tamura G, Sato M, Motoyama T. Age-related methylation of tumor suppressor and tumor-related genes: an analysis of autopsy samples. Oncogene. 2003;22(26):4128–33.

    Article  CAS  PubMed  Google Scholar 

  236. Sutherland KD, Lindeman GJ, Choong DY, et al. Differential hypermethylation of SOCS genes in ovarian and breast carcinomas. Oncogene. 2004;23(46):7726–33.

    Article  CAS  PubMed  Google Scholar 

  237. So K, Tamura G, Honda T, Homma N, et al. Multiple tumor suppressor genes are increasingly methylated with age in non-neoplastic gastric epithelia. Cancer Sci. 2006;97(11):1155–8.

    Article  CAS  PubMed  Google Scholar 

  238. Nishida N, Nagasaka T, Nishimura T, et al. Aberrant methylation of multiple tumor suppressor genes in aging liver, chronic hepatitis, and hepatocellular carcinoma. Hepatology. 2008;47(3):908–18.

    Article  CAS  PubMed  Google Scholar 

  239. Yuan Y, Qian ZR, Sano T, et al. Reduction of GSTP1 expression by DNA methylation correlates with clinicopathological features in pituitary adenomas. Mod Pathol. 2008;21(7):856–65.

    Article  CAS  PubMed  Google Scholar 

  240. Pilsner JR, Hall MN, Liu X, et al. Influence of prenatal arsenic exposure and newborn sex on global methylation of cord blood DNA. PLoS One. 2012;7(5):e37147.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  241. Majumdar S, Chanda S, Ganguli B, et al. Arsenic exposure induces genomic hypermethylation. Environ Toxicol. 2010;25(3):315–8.

    Article  CAS  PubMed  Google Scholar 

  242. Guo X, Chen X, Wang J, et al. Multi-generational impacts of arsenic exposure on genome-wide DNA methylation and the implications for arsenic-induced skin lesions. Environ Int. 2018;119:250–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  243. Kaushal A, Zhang H, Karmaus WJJ. Genome-wide DNA methylation at birth in relation to in utero arsenic exposure and the associated health in later life. Environ Health. 2017;16(1):50.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  244. Cowley M, Skaar DA, Jima DD, et al. Effects of cadmium exposure on DNA methylation at imprinting control regions and genome-wide in mothers and newborn children. Environ Health Perspect. 2018;126(3):037003.

    Article  PubMed  PubMed Central  Google Scholar 

  245. Hirao-Suzuki M, Takeda S, Kobayashi T, et al. Cadmium down-regulates apolipoprotein E (ApoE) expression during malignant transformation of rat liver cells: direct evidence for DNA hypermethylation in the promoter region of ApoE. J Toxicol Sci. 2018;43(9):537–43.

    Article  PubMed  Google Scholar 

  246. Virani S, Rentschler KM, Nishijo M, et al. DNA methylation is differentially associated with environmental cadmium exposure based on sex and smoking status. Chemosphere. 2016;145:284–90.

    Article  CAS  PubMed  Google Scholar 

  247. Wang TC, Song YS, Wang H, et al. Oxidative DNA damage and global DNA hypomethylation are related to folate deficiency in chromate manufacturing workers. J Hazard Mater. 2012;213–214:440–6.

    Article  PubMed  CAS  Google Scholar 

  248. Yang L, Xia B, Yang X, et al. Mitochondrial DNA hypomethylation in chrome plating workers. Toxicol Lett. 2016;243:1–6.

    Article  CAS  PubMed  Google Scholar 

  249. Lou J, Wang Y, Yao C, et al. Role of DNA methylation in cell cycle arrest induced by Cr (VI) in two cell lines. PLoS One. 2013;8(8):e71031.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  250. Cardenas A, Rifas-Shiman SL, Godderis L, et al. Prenatal exposure to mercury: associations with global DNA methylation and hydroxymethylation in cord blood and in childhood. Environ Health Perspect. 2017;125(8):087022.

    Article  PubMed  PubMed Central  Google Scholar 

  251. Cardenas A, Rifas-Shiman SL, Agha G, et al. Persistent DNA methylation changes associated with prenatal mercury exposure and cognitive performance during childhood. Sci Rep. 2017;7(1):288.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  252. Goodrich JM, Basu N, Franzblau A, Dolinoy DC. Mercury biomarkers and DNA methylation among Michigan dental professionals. Environ Mol Mutagen. 2013;54(3):195–203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  253. Zhang X, Chen X, Weirauch MT, et al. Diesel exhaust and house dust mite allergen lead to common changes in the airway methylome and hydroxymethylome. Environ Epigenet. 2018;4(3):dvy020.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  254. Ghosh K, Chatterjee B, Kanade SR. Lead induces the up-regulation of the protein arginine methyltransferase 5 possibly by its promoter demethylation. Biochem J. 2018;475(16):2653–66.

    Article  CAS  PubMed  Google Scholar 

  255. Liu X, Wu J, Shi W, et al. Lead induces genotoxicity via oxidative stress and promoter methylation of DNA repair genes in human lymphoblastoid TK6 cells. Med Sci Monitor. 2018;24:4295–304.

    Article  CAS  Google Scholar 

  256. Cheong A, Johnson SA, Howald EC, et al. Gene expression and DNA methylation changes in the hypothalamus and hippocampus of adult rats developmentally exposed to bisphenol A or ethinyl estradiol: a CLARITY-BPA consortium study. Epigenetics. 2018;13(7):704–20.

    Article  PubMed  PubMed Central  Google Scholar 

  257. Mostafavi N, Vermeulen R, Ghantous A, et al. Acute changes in DNA methylation in relation to 24 h personal air pollution exposure measurements: a panel study in four European countries. Environ Int. 2018;120:11–21.

    Article  CAS  PubMed  Google Scholar 

  258. Maghbooli Z, Hossein-Nezhad A, Adabi E, et al. Air pollution during pregnancy and placental adaptation in the levels of global DNA methylation. PLoS One. 2018;13(7):e0199772.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  259. Nawrot TS, Saenen ND, Schenk J, et al. Placental circadian pathway methylation and in utero exposure to fine particle air pollution. Environ Int. 2018;114:231–41.

    Article  CAS  PubMed  Google Scholar 

  260. Li J, Zhu X, Yu K, et al. Exposure to polycyclic aromatic hydrocarbons and accelerated DNA methylation aging. Environ Health Perspect. 2018;126(6):067005.

    Article  PubMed  PubMed Central  Google Scholar 

  261. Lee J, Kalia V, Perera F, et al. Prenatal airborne polycyclic aromatic hydrocarbon exposure, LINE1 methylation and child development in a Chinese cohort. Environ Int. 2017;99:315–20.

    Article  CAS  PubMed  Google Scholar 

  262. White AJ, Chen J, Teitelbaum SL, et al. Sources of polycyclic aromatic hydrocarbons are associated with gene-specific promoter methylation in women with breast cancer. Environ Res. 2016;145:93–100.

    Article  CAS  PubMed  Google Scholar 

  263. White N, Benton M, Kennedy D, et al. Accounting for cell lineage and sex effects in the identification of cell-specific DNA methylation using a Bayesian model selection algorithm. PLoS One. 2017;12(9):e0182455.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  264. Prince C, Hammerton G, Taylor AE, et al. Investigating the impact of cigarette smoking behaviours on DNA methylation patterns in adolescence. Hum Mol Genet. 2019;28(1):155–65.

    PubMed  Google Scholar 

  265. Witt SH, Frank J, Gilles M, et al. Impact on birth weight of maternal smoking throughout pregnancy mediated by DNA methylation. BMC Genomics. 2018;19(1):290.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  266. Cole E, Brown TA, Pinkerton KE, et al. Perinatal exposure to environmental tobacco smoke is associated with changes in DNA methylation that precede the adult onset of lung disease in a mouse model. Inhal Toxicol. 2017;29(10):435–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  267. Sziráki A, Tyshkovskiy A, Gladyshev VN. Global remodeling of the mouse DNA methylome during aging and in response to calorie restriction. Aging Cell. 2018;17(3):e12738.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  268. Kim CH, Lee EK, Choi YJ, et al. Short-term calorie restriction ameliorates genomewide, age-related alterations in DNA methylation. Aging Cell. 2016;15(6):1074–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  269. Chen PY, Ganguly A, Rubbi L, et al. Intrauterine calorie restriction affects placental DNA methylation and gene expression. Physiol Genomics. 2013;45(14):565–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  270. Pauwels S, Ghosh M, Duca RC, et al. Maternal intake of methyl-group donors affects DNA methylation of metabolic genes in infants. Clin Epigenet. 2017;9:16.

    Article  CAS  Google Scholar 

  271. Pauwels S, Duca C, Devlieger R, et al. Maternal methyl-group donor intake and global DNA (hydroxy)methylation before and during pregnancy. Nutrients. 2016;8(8):474.

    Article  PubMed Central  CAS  Google Scholar 

  272. Kok DE, Dhonukshe-Rutten R, Lute C, et al. The effects of long-term daily folic acid and vitamin B12 supplementation on genome-wide DNA methylation in elderly subjects. Clin Epigenet. 2015;7:121.

    Article  CAS  Google Scholar 

  273. Fang MZ, Wang Y, Ai N, et al. Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res. 2003;63(22):7563–70.

    CAS  PubMed  Google Scholar 

  274. Anderson CM, Gillespie SL, Thiele DK, et al. Effects of maternal vitamin D supplementation on the maternal and infant epigenome. Breastfeed Med. 2018;13(5):371–80.

    Article  PubMed  PubMed Central  Google Scholar 

  275. Zappe K, Pointner A, Switzeny OJ, et al. Counteraction of oxidative stress by vitamin E affects epigenetic regulation by increasing global methylation and gene expression of MLH1 and DNMT1 dose dependently in Caco-2 cells. Oxid Med Cell Longev. 2018;2018:3734250.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  276. Ramaiyan B, Talahalli RR. Dietary unsaturated fatty acids modulate maternal dyslipidemia-induced DNA methylation and histone acetylation in placenta and fetal liver in rats. Lipids. 2018;53(6):581–8.

    Article  CAS  PubMed  Google Scholar 

  277. Moody L, Chen H, Pan YX. Postnatal diet remodels hepatic DNA methylation in metabolic pathways established by a maternal high-fat diet. Epigenomics. 2017;9(11):1387–402.

    Article  CAS  PubMed  Google Scholar 

  278. Zhang Y, Wang H, Zhou D, et al. High-fat diet caused widespread epigenomic differences on hepatic methylome in rat. Physiol Genomics. 2015;47(10):514–23.

    Article  CAS  PubMed  Google Scholar 

  279. Nakatome M, Orii M, Hamajima M, et al. Methylation analysis of circadian clock gene promoters in forensic autopsy specimens. Legal Med (Tokyo). 2011;13(4):205–9.

    Article  CAS  Google Scholar 

  280. Jiang W, Li J, Zhang Z, et al. Epigenetic upregulation of alpha-synuclein in the rats exposed to methamphetamine. Eur J Pharmacol. 2014;745:243–8.

    Article  CAS  PubMed  Google Scholar 

  281. Itzhak Y, Ergui I, Young JI. Long-term parental methamphetamine exposure of mice influences behavior and hippocampal DNA methylation of the offspring. Mol Psychiatry. 2015;20(2):232–9.

    Article  CAS  PubMed  Google Scholar 

  282. Jayanthi S, McCoy MT, Chen B, et al. Methamphetamine downregulates striatal glutamate receptors via diverse epigenetic mechanisms. Biol Psychiatry. 2014;76(1):47–56.

    Article  CAS  PubMed  Google Scholar 

  283. Anier K, Malinovskaja K, Aonurm-Helm A, et al. DNA methylation regulates cocaine-induced behavioral sensitization in mice. Neuropsychopharmacology. 2010;35(12):2450–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  284. Pol Bodetto S, Carouge D, Fonteneau M, et al. Cocaine represses protein phosphatase-1Cβ through DNA methylation and methyl-CpG binding protein-2 recruitment in adult rat brain. Neuropharmacology. 2013;73:31–40.

    Article  CAS  PubMed  Google Scholar 

  285. Tian W, Zhao M, Li M, et al. Reversal of cocaine-conditioned place preference through methyl supplementation in mice: altering global DNA methylation in the prefrontal cortex. PLoS One. 2012;7:e33435.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  286. Carouge D, Host L, Aunis D, et al. CDKL5 is a brain MeCP2 target gene regulated by DNA methylation. Neurobiol Dis. 2010;38(3):414–24.

    Article  CAS  PubMed  Google Scholar 

  287. Ajonijebu DC, Abboussi O, Mabandla MV, et al. Differential epigenetic changes in the hippocampus and prefrontal cortex of female mice that had free access to cocaine. Metab Brain Dis. 2018;33(2):411–20.

    Article  CAS  PubMed  Google Scholar 

  288. Ebrahimi G, Asadikaram G, Akbari H, et al. Elevated levels of DNA methylation at the OPRM1 promoter region in men with opioid use disorder. Am J Drug Alcohol Abuse. 2018;44(2):193–9.

    Article  PubMed  Google Scholar 

  289. Chorbov VM, Todorov AA, Lynskey MT, et al. Elevated levels of DNA methylation at the OPRM1 promoter in blood and sperm from male opioid addicts. J Opioid Manag. 2011;7(4):258–64.

    Article  PubMed  PubMed Central  Google Scholar 

  290. McLaughlin P, Mactier H, Gillis C, et al. Increased DNA methylation of ABCB1, CYP2D6, and OPRM1 genes in newborn infants of methadone-maintained opioid-dependent mothers. J Pediatrics. 2017;190:180–184.e1.

    Article  CAS  Google Scholar 

  291. Groh A, Rhein M, Buchholz V, et al. Epigenetic effects of intravenous diacetylmorphine on the methylation of POMC and NR3C1. Neuropsychobiology. 2017;75(4):193–9.

    Article  CAS  PubMed  Google Scholar 

  292. Groh A, Jahn K, Burkert A, et al. Epigenetic regulation of the promotor region of vascular endothelial growth factor-A and nerve growth factor in opioid-maintained patients. Eur Addict Res. 2017;23(5):249–59.

    Article  PubMed  Google Scholar 

  293. Watson CT, Szutorisz H, Garg P, et al. Genome-wide DNA methylation profiling reveals epigenetic changes in the rat nucleus accumbens associated with cross-generational effects of adolescent THC exposure. Neuropsychopharmacology. 2015;40(13):2993–3005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  294. Gerra MC, Jayanthi S, Manfredini M, et al. Gene variants and educational attainment in cannabis use: mediating role of DNA methylation. Transl Psychiatry. 2018;8(1):23.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  295. Taqi MM, Bazov I, Watanabe H, et al. Prodynorphin CpG-SNPs associated with alcohol dependence: elevated methylation in the brain of human alcoholics. Addict Biol. 2011;16(3):499–509.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  296. Philibert RA, Gunter TD, Beach SR, et al. MAOA methylation is associated with nicotine and alcohol dependence in women. Am J Med Genet Part B Neuropsychiatric Genet. 2008;147B(5):565–70.

    Article  CAS  Google Scholar 

  297. Glahn A, Riera Knorrenschild R, Rhein M, et al. Alcohol-induced changes in methylation status of individual CpG sites, and serum levels of vasopressin and atrial natriuretic peptide in alcohol-dependent patients during detoxification treatment. Eur Addict Res. 2014;20(3):143–50.

    Article  PubMed  Google Scholar 

  298. Foroud T, Wetherill LF, Liang T, et al. Association of alcohol craving with alpha-synuclein (SNCA). Alcohol Clin Exp Res. 2007;31(4):537–45.

    CAS  PubMed  Google Scholar 

  299. Ji C, Nagaoka K, Zou J, et al. Chronic ethanol-mediated hepatocyte apoptosis links to decreased TET1 and 5-hydroxymethylcytosine formation. FASEB J. 2019;33(2):1824–35.

    Article  CAS  PubMed  Google Scholar 

  300. Frey S, Eichler A, Stonawski V, et al. Prenatal alcohol exposure is associated with adverse cognitive effects and distinct whole-genome DNA methylation patterns in primary school children. Front Behav Neurosci. 2018;12:125.

    Article  PubMed  PubMed Central  Google Scholar 

  301. Brückmann C, Islam SA, MacIsaac JL, et al. DNA methylation signatures of chronic alcohol dependence in purified CD3+ T-cells of patients undergoing alcohol treatment. Sci Rep. 2017;7(1):6605.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  302. Weng JT, Wu LS, Lee CS, et al. Integrative epigenetic profiling analysis identifies DNA methylation changes associated with chronic alcohol consumption. Comput Biol Med. 2015;64:299–306.

    Article  CAS  PubMed  Google Scholar 

  303. Heberlein A, Muschler M, Frieling H, et al. Epigenetic down regulation of nerve growth factor during alcohol withdrawal. Addict Biol. 2013;18(3):508–10.

    Article  CAS  PubMed  Google Scholar 

  304. Brückmann C, Di Santo A, Karle KN, et al. Validation of differential GDAP1 DNA methylation in alcohol dependence and its potential function as a biomarker for disease severity and therapy outcome. Epigenetics. 2016;11(6):456–63.

    Article  PubMed  PubMed Central  Google Scholar 

  305. Jasiewicz A, Rubiś B, Samochowiec J, et al. DAT1 methylation changes in alcohol-dependent individuals vs. controls. J Psychiatric Res. 2015;64:130–3.

    Article  Google Scholar 

  306. Fiano V, Trevisan M, Fasanelli F, et al. Methylation in host and viral genes as marker of aggressiveness in cervical lesions: analysis in 543 unscreened women. Gynecol Oncol. 2018;151(2):319–26. pii: S0090-8258(18)31161-2

    Article  CAS  PubMed  Google Scholar 

  307. Jin J, Xu H, Wu R, et al. Aberrant DNA methylation profile of hepatitis B virus infection. J Med Virol. 2019;91(1):81–92.

    Article  CAS  PubMed  Google Scholar 

  308. Nunes JM, Furtado MN, de Morais Nunes ER, et al. Modulation of epigenetic factors during the early stages of HIV-1 infection in CD4+ T cells in vitro. Virology. 2018;523:41–51.

    Article  CAS  PubMed  Google Scholar 

  309. Gao X, Zhang Y, Brenner H. Associations of Helicobacter pylori infection and chronic atrophic gastritis with accelerated epigenetic ageing in older adults. Br J Cancer. 2017;117(8):1211–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  310. Gupta H, Chaudhari S, Rai A, et al. Genetic and epigenetic changes in host ABCB1 influences malaria susceptibility to Plasmodium falciparum. PLoS One. 2017;12(4):e0175702.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  311. Mehta D, Bruenig D, Carrillo-Roa T, et al. Genomewide DNA methylation analysis in combat veterans reveals a novel locus for PTSD. Acta Psychiatr Scand. 2017;136(5):493–505.

    Article  CAS  PubMed  Google Scholar 

  312. Peng H, Zhu Y, Strachan E, et al. Childhood trauma, DNA methylation of stress-related genes, and depression: findings from two monozygotic twin studies. Psychosom Med. 2018;80(7):599–608.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  313. Wolf EJ, Logue MW, Morrison FG, et al. Posttraumatic psychopathology and the pace of the epigenetic clock: a longitudinal investigation. Psychol Med. 2018;13:1–10.

    Google Scholar 

  314. Song D, Qi W, Lv M, et al. Combined bioinformatics analysis reveals gene expression and DNA methylation patterns in osteoarthritis. Mol Med Rep. 2018;17(6):8069–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  315. Hughes A, Smart M, Gorrie-Stone T, Het a. Socioeconomic position and DNA methylation age acceleration across the lifecourse. Am J Epidemiol. 2018;187(11):2346–54.

    Article  PubMed  PubMed Central  Google Scholar 

  316. Swartz JR, Hariri AR, Williamson DE. An epigenetic mechanism links socioeconomic status to changes in depression-related brain function in high-risk adolescents. Mol Psychiatry. 2017;22(2):209–14.

    Article  CAS  PubMed  Google Scholar 

  317. Chan MA, Ciaccio CE, Gigliotti NM, et al. DNA methylation levels associated with race and childhood asthma severity. J Asthma. 2017;54(8):825–32.

    Article  CAS  PubMed  Google Scholar 

  318. Tehranifar P, Wu HC, Fan X, et al. Early life socioeconomic factors and genomic DNA methylation in mid-life. Epigenetics. 2013;8(1):23–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  319. Croce CM. Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 2009;10(10):704–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  320. Jovanović I, Zˇivkovic´ M, Jovanović J, et al. The co-inertia approach in identification of specific microRNA in early and advanced atherosclerosis plaque. Med Hypotheses. 2014;83:11–5.

    Article  PubMed  CAS  Google Scholar 

  321. Macha MA, Seshacharyulu P, Krishn SR, et al. MicroRNAs (miRNAs) as biomarker(s) for prognosis and diagnosis of gastrointestinal (GI) cancers. Curr Pharm Des. 2014;20(33):5287–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  322. Williams AH, Valdez G, Moresi V, et al. MicroRNA-206 delays ALS progression and promotes regeneration of neuromuscular synapses in mice. Science. 2009;326:1549–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  323. Hudson MB, Rahnert JA, Zheng B, et al. miR-182 attenuates atrophy-related gene expression by targeting FoxO3 in skeletal muscle. Am J Physiol Cell Physiol. 2014;307:C314–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  324. Vickers KC, Landstreet SR, Levin MG, et al. MicroRNA-223 coordinates cholesterol homeostasis. Proc Natl Acad Sci U S A. 2014;111(40):14518–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  325. Kumar S, Kim CW, Simmons RD, Jo H. Role of flow-sensitive microRNAs in endothelial dysfunction and atherosclerosis—“Mechanosensitive Athero-miRs”. Arterioscler Thromb Vasc Biol. 2014;34(10):2206–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Dina Bellizzi, Francesco Guarasci, Francesca Iannone, Giuseppe Passarino, and Giuseppina Rose, who are listed in alphabetical order, equally contributed to this work.

Authors and Affiliations

  1. Department of Biology, Ecology and Earth Science, University of Calabria, Rende, Italy

    Dina Bellizzi, Francesco Guarasci, Francesca Iannone, Giuseppe Passarino & Giuseppina Rose

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  1. Dina Bellizzi
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  2. Francesco Guarasci
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Correspondence to Giuseppe Passarino .

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    Calogero Caruso

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Bellizzi, D., Guarasci, F., Iannone, F., Passarino, G., Rose, G. (2019). Epigenetics and Ageing. In: Caruso, C. (eds) Centenarians. Springer, Cham. https://doi.org/10.1007/978-3-030-20762-5_7

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