Back to the future: Epigenetic clock plasticity towards healthy aging

Mechanisms of Ageing and Development

Volumn 174, Issue , 2018, Pages 18-29

  Declerck, Ken ^a   Vanden Berghe, Wim ^a  

^a UNIVERSITY OF ANTWERP   (Belgium)

Author keywords

Age; Aging; Clock; Diet; Disease; Epigenetic; Healthy; Inflammation; Lifestyle; Nutrition

Indexed keywords

DNA METHYLTRANSFERASE; HYDROCORTISONE; POLYCOMB GROUP PROTEIN;

ALL CAUSE MORTALITY; BODY MASS; CANCER INCIDENCE; CANCER MORTALITY; CARDIOVASCULAR MORTALITY; CPG ISLAND; DEGENERATIVE DISEASE; DNA METHYLATION; ENVIRONMENTAL FACTOR; EPIGENETIC CLOCK; EPIGENETICS; GENE EXPRESSION; HEALTHY AGING; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; LIFE EXTENSION; LIFE STRESS; LIFESTYLE; NONHUMAN; OBESITY; POSTTRAUMATIC STRESS DISORDER; PRIORITY JOURNAL; REVIEW; WHITE MATTER LESION; AGING; ANIMAL; GENETIC EPIGENESIS; PHYSIOLOGY;

AGING; ANIMALS; DNA METHYLATION; EPIGENESIS, GENETIC; HUMANS;

EID: 85040961623     PISSN: 00476374     EISSN: 18726216     Source Type: Journal    
DOI: 10.1016/j.mad.2018.01.002     Document Type: Review

References (186)

1. Afanas'ev, I., New nucleophilic mechanisms of ros-dependent epigenetic modifications: comparison of aging and cancer. Aging Dis. 5:1 (2014), 52–62.
2. Alisch, R.S., et al. Age-associated DNA methylation in pediatric populations. Genome Res. 22:4 (2012), 623–632.
3. Almen, M.S., et al. Genome-wide analysis reveals DNA methylation markers that vary with both age and obesity. Gene 548:1 (2014), 61–67.
4. Ambatipudi, S., et al. DNA methylome analysis identifies accelerated epigenetic ageing associated with postmenopausal breast cancer susceptibility. Eur. J. Cancer 75 (2017), 299–307.
5. Armstrong, N.J., et al. Aging: exceptional longevity and comparisons of the Hannum and Horvath epigenetic clocks. Epigenomics 9:5 (2017), 689–700.
6. Baubec, T., Schubeler, D., Genomic patterns and context specific interpretation of DNA methylation. Curr. Opin. Genet. Dev. 25 (2014), 85–92.
7. Baylis, D., et al. Understanding how we age: insights into inflammaging. Longev Healthspan, 2(1), 2013, 8.
8. Beerman, I., et al. Proliferation-dependent alterations of the DNA methylation landscape underlie hematopoietic stem cell aging. Cell Stem Cell 12:4 (2013), 413–425.
9. Bekaert, B., et al. Improved age determination of blood and teeth samples using a selected set of DNA methylation markers. Epigenetics 10:10 (2015), 922–930.
10. Bell, J.T., et al. Epigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population. PLoS Genet., 8(4), 2012, e1002629.
11. Bjornsson, H.T., et al. Intra-individual change over time in DNA methylation with familial clustering. JAMA 299:24 (2008), 2877–2883.
12. Boks, M.P., et al. Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder. Psychoneuroendocrinology 51 (2015), 506–512.
13. Bollati, V., et al. Decline in genomic DNA methylation through aging in a cohort of elderly subjects. Mech. Ageing Dev. 130:4 (2009), 234–239.
14. Bormann, F., et al. Reduced DNA methylation patterning and transcriptional connectivity define human skin aging. Aging Cell 15:3 (2016), 563–571.
15. Breitling, L.P., et al. Frailty is associated with the epigenetic clock but not with telomere length in a German cohort. Clin Epigenetics, 8, 2016, 21.
16. Brooks-Wilson, A.R., Genetics of healthy aging and longevity. Hum. Genet. 132:12 (2013), 1323–1338.
17. Bui, M., et al. Sharing a placenta is associated with a greater similarity in DNA methylation in monochorionic versus dichorionic twin pars in blood at age 14. Twin Res. Hum. Genet. 18:6 (2015), 680–685.
18. Busche, S., et al. Population whole-genome bisulfite sequencing across two tissues highlights the environment as the principal source of human methylome variation. Genome Biol., 16, 2015, 290.
19. Carroll, J.E., et al. Epigenetic aging and immune senescence in women with insomnia symptoms: findings from the women's health initiative study. Biol. Psychiatry 81:2 (2017), 136–144.
20. Chaix, R., et al. Epigenetic clock analysis in long-term meditators. Psychoneuroendocrinology 85 (2017), 210–214.
21. Chen, B.H., et al. DNA methylation-based measures of biological age: meta-analysis predicting time to death. Aging (Albany NY) 8:9 (2016), 1844–1865.
22. Chiacchiera, F., Piunti, A., Pasini, D., Epigenetic methylations and their connections with metabolism. Cell. Mol. Life Sci. 70:9 (2013), 1495–1508.
23. Christensen, B.C., et al. Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet., 5(8), 2009, e1000602.
24. Christiansen, L., et al. DNA methylation age is associated with mortality in a longitudinal Danish twin study. Aging Cell 15:1 (2016), 149–154.
25. Cole, J.J., et al. Diverse interventions that extend mouse lifespan suppress shared age-associated epigenetic changes at critical gene regulatory regions. Genome Biol., 18(1), 2017, 58.
26. Davis, E.G., et al. Accelerated DNA methylation age in adolescent girls: associations with elevated diurnal cortisol and reduced hippocampal volume. Transl. Psychiatry, 7(8), 2017, e1223.
27. Day, K., et al. Differential DNA methylation with age displays both common and dynamic features across human tissues that are influenced by CpG landscape. Genome Biol., 14(9), 2013, R102.
28. De Paoli-Iseppi, R., et al. Measuring animal age with DNA methylation: from humans to wild animals. Front. Genet., 8, 2017, 106.
29. Deaton, A.M., Bird, A., CpG islands and the regulation of transcription. Genes Dev. 25:10 (2011), 1010–1022.
30. Delatte, B., et al. Genome-wide hydroxymethylcytosine pattern changes in response to oxidative stress. Sci. Rep., 5, 2015, 12714.
31. Desai, M., Jellyman, J.K., Ross, M.G., Epigenomics: gestational programming and risk of metabolic syndrome. Int. J. Obes. (Lond.) 39:4 (2015), 633–641.
32. Durso, D.F., et al. Acceleration of leukocytes’ epigenetic age as an early tumor and sex-specific marker of breast and colorectal cancer. Oncotarget 8:14 (2017), 23237–23245.
33. Feil, R., Fraga, M.F., Epigenetics and the environment: emerging patterns and implications. Nat. Rev. Genet. 13:2 (2012), 97–109.
34. Fernandez, A.F., et al. H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells. Genome Res. 25:1 (2015), 27–40.
35. Florath, I., et al. Cross-sectional and longitudinal changes in DNA methylation with age: an epigenome-wide analysis revealing over 60 novel age-associated CpG sites. Hum. Mol. Genet. 23:5 (2014), 1186–1201.
36. Fraga, M.F., et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc. Natl. Acad. Sci. U. S. A. 102:30 (2005), 10604–10609.
37. Franceschi, C., Campisi, J., Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J. Gerontol. A Biol. Sci. Med. Sci. 69:Suppl 1 (2014), S4–9.
38. Freire-Aradas, A., et al. Development of a methylation marker set for forensic age estimation using analysis of public methylation data and the Agena Bioscience EpiTYPER system. Forensic Sci. Int. Genet. 24 (2016), 65–74.
39. Freire-Aradas, A., Phillips, C., Lareu, M.V., Forensic individual age estimation with DNA: From initial approaches to methylation tests. Forensic Sci. Rev. 29:2 (2017), 121–144.
40. Fries, G.R., Bauer, I.E., Scaini, G., Wu, M.J., Kazimi, I.F., Valvassori, S.S., Zunta-Soares, G., Walss-Bass, C., Soares, J.C., Quevedo, J., Accelerated epigenetic aging and mitochondrial DNA copy number in bipolar disorder. Transl. Psychiatry, 7(December (12)), 2017, 1283 PMID:29225347.
41. Gao, X., et al. Relationship of tobacco smoking and smoking-related DNA methylation with epigenetic age acceleration. Oncotarget 7:30 (2016), 46878–46889.
42. 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 117:October (8) (2017), 1211–1214, 10.1038/bjc.2017.314 Epub 2017 Sep 12. PMID: 28898235.
43. Gautrey, H.E., et al. DNA methylation abnormalities at gene promoters are extensive and variable in the elderly and phenocopy cancer cells. FASEB J. 28:7 (2014), 3261–3272.
44. Girchenko, P., et al. Associations between maternal risk factors of adverse pregnancy and birth outcomes and the offspring epigenetic clock of gestational age at birth. Clin. Epigenetics, 9, 2017, 49.
45. Gluckman, P.D., Hanson, M.A., Buklijas, T., A conceptual framework for the developmental origins of health and disease. J. Dev. Origins Health Dis. 1:1 (2010), 6–18.
46. Gomes, M.V., et al. Age-related changes in the global DNA methylation profile of leukocytes are linked to nutrition but are not associated with the MTHFR C677T genotype or to functional capacities. PLoS One, 7(12), 2012, e52570.
47. Gordon, L., et al. Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors: subject to tissue-specific influence. Genome Res. 22:8 (2012), 1395–1406.
48. Gross, A.M., et al. Methylome-wide analysis of chronic HIV infection reveals five-year increase in biological age and epigenetic targeting of HLA. Mol. Cell 62:2 (2016), 157–168.
49. Hahn, O., et al. Dietary restriction protects from age-associated DNA methylation and induces epigenetic reprogramming of lipid metabolism. Genome Biol., 18(1), 2017, 56.
50. Hamano, Y., et al. Forensic age prediction for dead or living samples by use of methylation-sensitive high resolution melting. Leg. Med. (Tokyo) 21 (2016), 5–10.
51. Hannum, G., et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol. Cell 49:2 (2013), 359–367.
52. Hanson, M.A., Gluckman, P.D., Early developmental conditioning of later health and disease: physiology or pathophysiology?. Physiol. Rev. 94:4 (2014), 1027–1076.
53. Herbstman, J.B., et al. Predictors and consequences of global DNA methylation in cord blood and at three years. PLoS One, 8(9), 2013, e72824.
54. Hernandez, D.G., et al. Distinct DNA methylation changes highly correlated with chronological age in the human brain. Hum. Mol. Genet. 20:6 (2011), 1164–1172.
55. Heyn, H., et al. Distinct DNA methylomes of newborns and centenarians. Proc. Natl. Acad. Sci. U. S. A. 109:26 (2012), 10522–10527.
56. Hodgson, K., et al. Epigenetic age acceleration assessed with human white-matter images. J. Neurosci. 37:18 (2017), 4735–4743.
57. Hong, S.R., et al. DNA methylation-based age prediction from saliva: high age predictability by combination of 7 CpG markers. Forensic Sci. Int. Genet. 29 (2017), 118–125.
58. Horsburgh, S., et al. Exercise and inflammation-related epigenetic modifications: focus on DNA methylation. Exerc. Immunol. Rev. 21 (2015), 26–41.
59. Horvath, S., Levine, A.J., HIV-1 infection accelerates age according to the epigenetic clock. J. Infect. Dis. 212:10 (2015), 1563–1573.
60. Horvath, S., Ritz, B.R., Increased epigenetic age and granulocyte counts in the blood of Parkinson's disease patients. Aging (Albany NY) 7:12 (2015), 1130–1142.
61. Horvath, S., et al. Aging effects on DNA methylation modules in human brain and blood tissue. Genome Biol., 13(10), 2012, R97.
62. Horvath, S., et al. Obesity accelerates epigenetic aging of human liver. Proc. Natl. Acad. Sci. U. S. A. 111:43 (2014), 15538–15543.
63. Horvath, S., et al. Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring. Aging (Albany NY) 7:12 (2015), 1159–1170.
64. Horvath, S., et al. The cerebellum ages slowly according to the epigenetic clock. Aging (Albany NY) 7:5 (2015), 294–306.
65. Horvath, S., et al. Accelerated epigenetic aging in Down syndrome. Aging Cell 14:3 (2015), 491–495.
66. Horvath, S., et al. An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease. Genome Biol., 17(1), 2016, 171.
67. Horvath, S., et al. Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels. Aging (Albany NY) 8:7 (2016), 1485–1512.
68. Horvath, S., DNA methylation age of human tissues and cell types. Genome Biol., 14(10), 2013, R115.
69. Horvath, S., Erratum to: DNA methylation age of human tissues and cell types. Genome Biol., 16, 2015, 96.
70. Huang, Y., et al. Developing a DNA methylation assay for human age prediction in blood and bloodstain. Forensic Sci. Int. Genet. 17 (2015), 129–136.
71. Huen, K., et al. Effects of age: sex, and persistent organic pollutants on DNA methylation in children. Environ. Mol. Mutagen. 55:3 (2014), 209–222.
72. Illingworth, R.S., Bird, A.P., CpG islands–a rough guide. FEBS Lett. 583:11 (2009), 1713–1720.
73. Issa, J.P., Aging and epigenetic drift: a vicious cycle. J. Clin. Invest. 124:1 (2014), 24–29.
74. Jazwinski, S.M., Kim, S., Metabolic and genetic markers of biological age. Front. Genet., 8, 2017, 64.
75. Jenny, N.S., Inflammation in aging: cause, effect, or both?. Discov. Med. 13:73 (2012), 451–460.
76. Jintaridth, P., Mutirangura, A., Distinctive patterns of age-dependent hypomethylation in interspersed repetitive sequences. Physiol. Genomics 41:2 (2010), 194–200.
77. Johnson, K.C., et al. Age-related DNA methylation in normal breast tissue and its relationship with invasive breast tumor methylation. Epigenetics 9:2 (2014), 268–275.
78. Jones, M.J., Goodman, S.J., Kobor, M.S., DNA methylation and healthy human aging. Aging Cell 14:6 (2015), 924–932.
79. Jones, P.A., Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat. Rev. Genet. 13:7 (2012), 484–492.
80. Jovanovic, T., et al. Exposure to violence accelerates epigenetic aging in children. Sci. Rep., 7(1), 2017, 8962.
81. Jung, M., Pfeifer, G.P., Aging and DNA methylation. BMC Biol., 13, 2015, 7.
82. Kananen, L., et al. Cytomegalovirus infection accelerates epigenetic aging. Exp. Gerontol. 72 (2015), 227–229.
83. Kananen, L., et al. The trajectory of the blood DNA methylome ageing rate is largely set before adulthood: evidence from two longitudinal studies. Age (Dordr.), 38(3), 2016, 65.
84. Kim, S., et al. The frailty index outperforms DNA methylation age and its derivatives as an indicator of biological age. Geroscience 39:1 (2017), 83–92.
85. Knight, A.K., et al. An epigenetic clock for gestational age at birth based on blood methylation data. Genome Biol., 17(1), 2016, 206.
86. Kong, Y., Trabucco, S.E., Zhang, H., Oxidative stress, mitochondrial dysfunction and the mitochondria theory of aging. Interdiscip. Top. Gerontol. 39 (2014), 86–107.
87. Levine, M.E., et al. DNA methylation age of blood predicts future onset of lung cancer in the women's health initiative. Aging (Albany NY) 7:9 (2015), 690–700.
88. Levine, M.E., et al. Epigenetic age of the pre-frontal cortex is associated with neuritic plaques: amyloid load, and Alzheimer's disease related cognitive functioning. Aging (Albany NY) 7:12 (2015), 1198–1211.
89. Levine, A.J., et al. Accelerated epigenetic aging in brain is associated with pre-mortem HIV-associated neurocognitive disorders. J. Neurovirol. 22:3 (2016), 366–375.
90. Levine, M.E., et al. Menopause accelerates biological aging. Proc. Natl. Acad. Sci. U. S. A. 113:33 (2016), 9327–9332.
91. Li, S., et al. Genetic and environmental causes of variation in the difference between biological age based on DNA methylation and chronological age for middle-aged women. Twin Res Hum Genet 18:6 (2015), 720–726.
92. Ligthart, S., et al. DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases. Genome Biol., 17(1), 2016, 255.
93. Lillycrop, K.A., et al. DNA methylation: ageing and the influence of early life nutrition. Proc. Nutr. Soc. 73:3 (2014), 413–421.
94. Lin, Q., et al. DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy. Aging (Albany NY) 8:2 (2016), 394–401.
95. Lopez-Otin, C., et al. The hallmarks of aging. Cell 153:6 (2013), 1194–1217.
96. Lowe, D., Horvath, S., Raj, K., Epigenetic clock analyses of cellular senescence and ageing. Oncotarget 7:8 (2016), 8524–8531.
97. Lu, A.T., et al. Genetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum. Nat. Commun., 7, 2016, 10561.
98. Lu, A.T., et al. Genetic architecture of epigenetic and neuronal ageing rates in human brain regions. Nat. Commun., 8, 2017, 15353.
99. Maegawa, S., et al. Caloric restriction delays age-related methylation drift. Nat. Commun., 8(1), 2017, 539.
100. Maierhofer, A., et al. Accelerated epigenetic aging in Werner syndrome. Aging (Albany NY) 9:4 (2017), 1143–1152.
101. Mangino, M., Genomics of ageing in twins. Proc. Nutr. Soc. 73:4 (2014), 526–531.
102. Marioni, R.E., et al. DNA methylation age of blood predicts all-cause mortality in later life. Genome Biol., 16, 2015, 25.
103. Marioni, R.E., et al. The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936. Int. J. Epidemiol. 44:4 (2015), 1388–1396.
104. Marioni, R.E., et al. The epigenetic clock and telomere length are independently associated with chronological age and mortality. Int. J. Epidemiol., 2016.
105. Martino, D., et al. Longitudinal, genome-scale analysis of DNA methylation in twins from birth to 18 months of age reveals rapid epigenetic change in early life and pair-specific effects of discordance. Genome Biol., 14(5), 2013, R42.
106. Marttila, S., et al. Ageing-associated changes in the human DNA methylome: genomic locations and effects on gene expression. BMC Genom., 16, 2015, 179.
107. Mayne, B.T., et al. Accelerated placental aging in early onset preeclampsia pregnancies identified by DNA methylation. Epigenomics 9:3 (2017), 279–289.
108. McKinney, B.C., et al. DNA methylation age is not accelerated in brain or blood of subjects with schizophrenia. Schizophr. Res., 2017.
109. McKinney, B.C., et al. DNA methylation evidence against the accelerated aging hypothesis of schizophrenia. NPJ Schizophr., 3, 2017, 13.
110. Mentch, S.J., Locasale, J.W., One-carbon metabolism and epigenetics: understanding the specificity. Ann. N.Y. Acad. Sci. 1363 (2016), 91–98.
111. Milagro, F.I., et al. Dietary factors, epigenetic modifications and obesity outcomes: progresses and perspectives. Mol. Aspects Med. 34:4 (2013), 782–812.
112. Miller, G.E., et al. Self-control forecasts better psychosocial outcomes but faster epigenetic aging in low-SES youth. Proc. Natl. Acad. Sci. U. S. A. 112:33 (2015), 10325–10330.
113. Murabito, J.M., Yuan, R., Lunetta, K.L., The search for longevity and healthy aging genes: insights from epidemiological studies and samples of long-lived individuals. J. Gerontol. A. Biol. Sci. Med. Sci. 67:5 (2012), 470–479.
114. Needham, B.L., et al. Leukocyte telomere length and mortality in the national health and nutrition examination survey: 1999–2002. Epidemiology 26:4 (2015), 528–535.
115. Nevalainen, T., et al. Obesity accelerates epigenetic aging in middle-aged but not in elderly individuals. Clin. Epigenetics, 9, 2017, 20.
116. Noreen, F., et al. Modulation of age- and cancer-associated DNA methylation change in the healthy colon by aspirin and lifestyle. J. Natl. Cancer Inst., 106(7), 2014.
117. Ollikainen, M., et al. DNA methylation analysis of multiple tissues from newborn twins reveals both genetic and intrauterine components to variation in the human neonatal epigenome. Hum. Mol. Genet. 19:21 (2010), 4176–4188.
118. Osborn, O., Olefsky, J.M., The cellular and signaling networks linking the immune system and metabolism in disease. Nat. Med. 18:3 (2012), 363–374.
119. Panickar, K.S., Jewell, D.E., The beneficial role of anti-inflammatory dietary ingredients in attenuating markers of chronic low-grade inflammation in aging. Horm. Mol. Biol. Clin. Invest. 23:2 (2015), 59–70.
120. Park, J.L., et al. Identification and evaluation of age-correlated DNA methylation markers for forensic use. Forensic Sci. Int. Genet. 23 (2016), 64–70.
121. Perna, L., et al. Epigenetic age acceleration predicts cancer, cardiovascular, and all-cause mortality in a German case cohort. Clin. Epigenetics, 8, 2016, 64.
122. Peters, M.J., et al. The transcriptional landscape of age in human peripheral blood. Nat. Commun., 6, 2015, 8570.
123. Petkovich, D.A., et al. Using DNA methylation profiling to evaluate biological age and longevity interventions. Cell Metab. 25:4 (2017), 954–960 (e6).
124. Pirazzini, C., et al. Space/population and time/age in DNA methylation variability in humans: a study on IGF2/H19 locus in different Italian populations and in mono- and di-zygotic twins of different age. Aging (Albany NY) 4:7 (2012), 509–520.
125. Portela, A., Esteller, M., Epigenetic modifications and human disease. Nat. Biotechnol. 28:10 (2010), 1057–1068.
126. Quach, A., et al. Epigenetic clock analysis of diet: exercise, education, and lifestyle factors. Aging (Albany NY) 9:2 (2017), 419–446.
127. Raina, A., et al. Cerebral white matter hyperintensities on MRI and acceleration of epigenetic aging: the atherosclerosis risk in communities study. Clin. Epigenetics, 9, 2017, 21.
128. Rakyan, V.K., et al. Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains. Genome Res. 20:4 (2010), 434–439.
129. Rang, F.J., Boonstra, J., Causes and consequences of age-related changes in DNA methylation: a role for ROS?. Biology (Basel) 3:2 (2014), 403–425.
130. Reuter, S., et al. Oxidative stress, inflammation, and cancer: how are they linked?. Free Radic. Biol. Med. 49:11 (2010), 1603–1616.
131. Reynolds, L.M., et al. Age-related variations in the methylome associated with gene expression in human monocytes and T cells. Nat. Commun., 5, 2014, 5366.
132. Reynolds, L.M., et al. Transcriptomic profiles of aging in purified human immune cells. BMC Genom., 16, 2015, 333.
133. Rizvi, S., Raza, S.T., Mahdi, F., Telomere length variations in aging and age-related diseases. Curr. Aging Sci. 7:3 (2014), 161–167.
134. Rode, L., Nordestgaard, B.G., Bojesen, S.E., Peripheral blood leukocyte telomere length and mortality among 64,637 individuals from the general population. J. Natl. Cancer Inst., 107(6), 2015, djv074.
135. Salminen, A., et al. Krebs cycle intermediates regulate DNA and histone methylation: epigenetic impact on the aging process. Ageing Res. Rev. 16 (2014), 45–65.
136. Sanders, J.L., Newman, A.B., Telomere length in epidemiology: a biomarker of aging, age-related disease, both, or neither?. Epidemiol. Rev. 35 (2013), 112–131.
137. Schell, J.C., Rutter, J., Mitochondria link metabolism and epigenetics in haematopoiesis. Nat. Cell. Biol. 19:6 (2017), 589–591.
138. Schubeler, D., ESCI award lecture: regulation, function and biomarker potential of DNA methylation. Eur. J. Clin. Invest. 45:3 (2015), 288–293.
139. Sehl, M.E., et al. DNA methylation age is elevated in breast tissue of healthy women. Breast Cancer Res. Treat. 164:1 (2017), 209–219.
140. Shah, S., et al. Genetic and environmental exposures constrain epigenetic drift over the human life course. Genome Res. 24:11 (2014), 1725–1733.
141. Shanmugam, M.K., Sethi, G., Role of epigenetics in inflammation-associated diseases. Subcell. Biochem. 61 (2013), 627–657.
142. Simons, R.L., et al. Economic hardship and biological weathering: the epigenetics of aging in a U.S. sample of black women. Soc. Sci. Med. 150 (2016), 192–200.
143. Simpkin, A.J., et al. Prenatal and early life influences on epigenetic age in children: a study of mother-offspring pairs from two cohort studies. Hum. Mol. Genet. 25:1 (2016), 191–201.
144. Simpkin, A.J., et al. Are objective measures of physical capability related to accelerated epigenetic age? Findings from a British birth cohort. BMJ Open, 7(10), 2017, e016708.
145. Simpkin, A.J., et al. The epigenetic clock and physical development during childhood and adolescence: longitudinal analysis from a UK birth cohort. Int. J. Epidemiol. 46:2 (2017), 549–558.
146. Soares Bispo Santos Silva, D., et al. Evaluation of DNA methylation markers and their potential to predict human aging. Electrophoresis 36:15 (2015), 1775–1780.
147. Soriano-Tarraga, C., et al. Biological age is better than chronological as predictor of 3-month outcome in ischemic stroke. Neurology 89:8 (2017), 830–836.
148. Starnawska, A., et al. Blood DNA methylation age is not associated with cognitive functioning in middle-aged monozygotic twins. Neurobiol. Aging 50 (2017), 60–63.
149. Steegenga, W.T., et al. Genome-wide age-related changes in DNA methylation and gene expression in human PBMCs. Age (Dordr), 36(3), 2014, 9648.
150. Stubbs, T.M., et al. Multi-tissue DNA methylation age predictor in mouse. Genome Biol., 18(1), 2017, 68.
151. Svensson, J., et al. Leukocyte telomere length is not associated with mortality in older men. Exp. Gerontol. 57 (2014), 6–12.
152. Szarc vel Szic, K., et al. From inflammaging to healthy aging by dietary lifestyle choices: is epigenetics the key to personalized nutrition?. Clin. Epigenetics, 2015, 33.
153. Tahiliani, M., et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324:5929 (2009), 930–935.
154. Talens, R.P., et al. Epigenetic variation during the adult lifespan: cross-sectional and longitudinal data on monozygotic twin pairs. Aging Cell 11:4 (2012), 694–703.
155. Tan, Q., et al. Twins for epigenetic studies of human aging and development. Ageing Res. Rev. 12:1 (2013), 182–187.
156. Tan, Q., et al. Epigenetic drift in the aging genome: a ten-year follow-up in an elderly twin cohort. Int. J. Epidemiol. 45:4 (2016), 1146–1158.
157. Teh, A.L., et al. The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes. Genome Res. 24:7 (2014), 1064–1074.
158. Teschendorff, A.E., et al. Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer. Genome Res. 20:4 (2010), 440–446.
159. Thompson, M.J., et al. An epigenetic aging clock for dogs and wolves. Aging (Albany NY) 9:3 (2017), 1055–1068.
160. Tserel, L., et al. Age-related profiling of DNA methylation in CD8+ T cells reveals changes in immune response and transcriptional regulator genes. Sci. Rep., 5, 2015, 13107.
161. van Dongen, J., et al. Genetic and environmental influences interact with age and sex in shaping the human methylome. Nat. Commun., 7, 2016, 11115.
162. van Eijk, K.R., et al. Genetic analysis of DNA methylation and gene expression levels in whole blood of healthy human subjects. BMC Genom., 13, 2012, 636.
163. van der Wijst, M.G., Rots, M.G., Mitochondrial epigenetics: an overlooked layer of regulation?. Trends Genet. 31:7 (2015), 353–356.
164. Vickers, M.H., Early life nutrition: epigenetics and programming of later life disease. Nutrients 6:6 (2014), 2165–2178.
165. Vidaki, A., et al. DNA methylation-based forensic age prediction using artificial neural networks and next generation sequencing. Forensic Sci. Int. Genet. 28 (2017), 225–236.
166. Voisey, J., et al. Epigenetic analysis confirms no accelerated brain aging in schizophrenia. NPJ Schizophr., 3(1), 2017, 26.
167. Wang, Y., et al. The identification of age-associated cancer markers by an integrative analysis of dynamic DNA methylation changes. Sci. Rep., 6, 2016, 22722.
168. Wang, T., et al. Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment. Genome Biol., 18(1), 2017, 57.
169. Weidner, C.I., et al. Aging of blood can be tracked by DNA methylation changes at just three CpG sites. Genome Biol., 15(2), 2014, R24.
170. West, J., et al. An integrative network algorithm identifies age-associated differential methylation interactome hotspots targeting stem-cell differentiation pathways. Sci. Rep., 3, 2013, 1630.
171. Wolf, E.J., et al. Accelerated DNA methylation age: associations with PTSD and neural integrity. Psychoneuroendocrinology 63 (2016), 155–162.
172. Wong, C.C., et al. A longitudinal study of epigenetic variation in twins. Epigenetics 5:6 (2010), 516–526.
173. Xu, Z., Taylor, J.A., Genome-wide age-related DNA methylation changes in blood and other tissues relate to histone modification, expression and cancer. Carcinogenesis 35:2 (2014), 356–364.
174. Xu, C., et al. A novel strategy for forensic age prediction by DNA methylation and support vector regression model. Sci. Rep., 5, 2015, 17788.
175. Yang, Z., et al. Correlation of an epigenetic mitotic clock with cancer risk. Genome Biol., 17(1), 2016, 205.
176. Yi, S.H., et al. Isolation and identification of age-related DNA methylation markers for forensic age-prediction. Forensic Sci. Int. Genet. 11 (2014), 117–125.
177. Yi, S.H., et al. Age-related DNA methylation changes for forensic age-prediction. Int. J. Legal Med. 129:2 (2015), 237–244.
178. Yuan, T., et al. An integrative multi-scale analysis of the dynamic DNA methylation landscape in aging. PLoS Genet., 11(2), 2015, e1004996.
179. Zannas, A.S., et al. Lifetime stress accelerates epigenetic aging in an urban, African American cohort: relevance of glucocorticoid signaling. Genome Biol., 16, 2015, 266.
180. Zbiec-Piekarska, R., et al. Examination of DNA methylation status of the ELOVL2 marker may be useful for human age prediction in forensic science. Forensic Sci. Int. Genet. 14 (2015), 161–167.
181. Zbiec-Piekarska, R., et al. Development of a forensically useful age prediction method based on DNA methylation analysis. Forensic Sci. Int. Genet. 17 (2015), 173–179.
182. Zheng, S.C., Widschwendter, M., Teschendorff, A.E., Epigenetic drift: epigenetic clocks and cancer risk. Epigenomics 8:5 (2016), 705–719.
183. Zheng, Y., et al. Blood epigenetic age may predict cancer incidence and mortality. EBioMedicine 5 (2016), 68–73.
184. Zhu, Z.Z., et al. Predictors of global methylation levels in blood DNA of healthy subjects: a combined analysis. Int. J. Epidemiol. 41:1 (2012), 126–139.
185. Zubakov, D., et al. Human age estimation from blood using mRNA, DNA, methylation, DNA rearrangement, and telomere length. Forensic Sci. Int. Genet. 24 (2016), 33–43.
186. Zykovich, A., et al. Genome-wide DNA methylation changes with age in disease-free human skeletal muscle. Aging Cell 13:2 (2014), 360–366.