DNA methylation-based biomarkers and the epigenetic clock theory of ageing

Nature Reviews Genetics

Volumn 19, Issue 6, 2018, Pages 371-384

  Horvath, Steve ^a,b   Raj, Kenneth ^c  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c Centre for Radiation Chemical and Environmental Hazards Public Health England   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MARKER;

AGING; BLOOD SAMPLING; CELL DIFFERENTIATION; CELL POPULATION; CELL PROLIFERATION; CIRCADIAN RHYTHM; COMPARATIVE STUDY; DNA METHYLATION; EPIGENETICS; GENE EXPRESSION; HUMAN; MORBIDITY; MORTALITY RISK; NEXT GENERATION SEQUENCING; NONHUMAN; PREDICTION; PRIORITY JOURNAL; REVIEW; ANIMAL; GENETIC EPIGENESIS; PHYSIOLOGY;

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

EID: 85045201945     PISSN: 14710056     EISSN: 14710064     Source Type: Journal    
DOI: 10.1038/s41576-018-0004-3     Document Type: Review

References (153)

1. Baker, G., Sprott, R. Biomarkers of aging. Exp. Gerontol. 23, 223-239 (1988).
2. Warner, H. R. The future of aging interventions. J. Gerontol. A Biol Sci. Med. Sci. 59, B692-B696 (2004)
3. Laird, P. W. Principles and challenges of genome-wide DNA methylation analysis. Nat. Rev. Genet. 11, 191-203 (2010).
4. Tibshirani, R. Regression shrinkage and selection via the Lasso. J. Royal Stat. Soc. B 58, 267-288 (1996).
5. Zou, H., Hastie, T. Regularization and variable selection via the elastic net. J. Royal Stat. Soc. B 67, 301-320 (2005).
6. Edgar, R., Domrachev, M., Lash, A. E. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 30, 207-210 (2002)
7. The Cancer Genome Atlas Research Netwok et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat. Genet. 45, 1113-1120 (2013).
8. Horvath, S. DNA methylation age of human tissues and cell types. Genome Biol. 14, R115 (2013).
9. Horvath, S. et al. Accelerated epigenetic aging in Down syndrome. Aging Cell 14, 491-495 (2015).
10. Maierhofer, A. et al. Accelerated epigenetic aging in Werner syndrome. Aging 9, 1143-1152 (2017).
11. Horvath, S. et al. An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease. Genome Biol. 17, 171 (2016).
12. Levine, M. E. et al. Menopause accelerates biological aging. Proc. Natl Acad. Sci. USA 113, 9327-9332 (2016).
13. Quach, A. et al. Epigenetic clock analysis of diet, exercise, education, and lifestyle factors. Aging 9, 419-446 (2017).
14. Huh, C. J. et al. Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblasts. eLife 5, e18648 (2016).
15. Jylhävä, J., Pedersen, N. L., Hägg, S. Biological age predictors. EBioMedicine 21, 29-36 (2017).
16. Lee, H. Y., Lee, S. D., Shin, K.-J. Forensic DNA methylation profiling from evidence material for investigative leads. BMB Rep. 49, 359-369 (2016).
17. Berdyshev, G., Korotaev, G., Boiarskikh, G., Vaniushin, B. Nucleotide composition of DNA and RNA from somatic tissues of humpback and its changes during spawning. Biokhimiia 31, 88-993 (1967).
18. Ahuja, N., Li, Q., Mohan, A. L., Baylin, S. B., Issa, J. P. Aging and DNA methylation in colorectal mucosa and cancer. Cancer Res. 58, 5489-5494 (1998).
19. Rakyan, V. K. et al. Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains. Genome Res. 20, 434-439 (2010).
20. 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, 440-446 (2010).
21. Hernandez, D. et al. Distinct DNA methylation changes highly correlated with chronological age in the human brain. Hum. Mol. Genet. 20, 1164-1172 (2011).
22. 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, e1002629 (2012).
23. Christensen, B. et al. Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet. 5, e1000602 (2009).
24. Maegawa, S. et al. Widespread and tissue specific age-related DNA methylation changes in mice. Genome Res. 20, 332-340 (2010).
25. Jung, M., Pfeifer, G. P. Aging and DNA methylation. BMC Biol. 13, 7 (2015).
26. Fraga, M. F., Esteller, M. Epigenetics and aging: The targets and the marks. Trends Genet. 23, 413-418 (2007).
27. Fraga, M. F., Agrelo, R., Esteller, M. Cross-talk between aging and cancer. Ann. NY Acad. Sci. 1100, 60-74 (2007).
28. Bollati, V. et al. Decline in genomic DNA methylation through aging in a cohort of elderly subjects. Mech. Ageing Dev. 130, 234-239 (2009).
29. Mugatroyd, C., Wu, Y., Bockmühl, Y., Spengler, D. The Janus face of DNA methylation in aging. Aging 2, 107-110 (2010).
30. Rodríguez-Rodero, S., Fernández-Morera, J., Fernandez, A., Menéndez-Torre, E., Fraga, M. Epigenetic regulation of aging. Discov. Med. 10, 225-233 (2010).
31. Horvath, S. et al. Aging effects on DNA methylation modules in human brain and blood tissue. Genome Biol. 13, R97 (2012).
32. Zheng, S. C., Widschwendter, M., Teschendorff, A. E. Epigenetic drift, epigenetic clocks and cancer risk. Epigenomics 8, 705-719 (2016).
33. Bocklandt, S. et al. Epigenetic predictor of age. PLoS ONE 6, e14821 (2011).
34. Hannum, G. et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol. Cell 49, 359-367 (2013).
35. 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, 191-201 (2016).
36. 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, 549-558 (2017).
37. Marioni, R. et al. DNA methylation age of blood predicts all-cause mortality in later life. Genome Biol. 16, 25 (2015).
38. Chen, B. H. et al. DNA methylation-based measures of biological age: Meta-analysis predicting time to death. Aging 8, 1844-1865 (2016).
39. Koch, C., Wagner, W. Epigenetic-aging-signature to determine age in different tissues. Aging 3, 1018-1027 (2011).
40. Garagnani, P. et al. Methylation of ELOVL2 gene as a new epigenetic marker of age. Aging Cell 11, 1132-1134 (2012).
41. Weidner, C. I. et al. Aging of blood can be tracked by DNA methylation changes at just three CpG sites. Genome Biol. 15, R24 (2014).
42. Bekaert, B., Kamalandua, A., Zapico, S. C., Van de Voorde, W., Decorte, R. Improved age determination of blood and teeth samples using a selected set of DNA methylation markers. Epigenetics 10, 922-930 (2015).
43. Hamano, Y. et al. Forensic age prediction for dead or living samples by use of methylation-sensitive high resolution melting. Leg. Med. 21, 5-10 (2016).
44. Zbiec-Piekarska, R. et al. Development of a forensically useful age prediction method based on DNA methylation analysis. Forensic Sci. Int. Genet. 17, 173-179 (2015).
45. Bormann, F. et al. Reduced DNA methylation patterning and transcriptional connectivity define human skin aging. Aging Cell 15, 563-571 (2016).
46. Florath, I., Butterbach, K., Muller, H., Bewerunge-Hudler, M., Brenner, H. 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, 1186-1201 (2014).
47. Lee, H. Y. et al. Epigenetic age signatures in the forensically relevant body fluid of semen: A preliminary study. Forensic Sci. Int. Genet. 19, 28-34 (2015).
48. Lin, Q. et al. DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy. Aging 8, 394-401 (2016).
49. 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, 720-726 (2015).
50. Bacalini, M. G. et al. Systemic age-associated DNA hypermethylation of ELOVL2 gene: In vivo and in vitro evidences of a cell replication process. J. Gerontol. A Biol Sci. Med. Sci. 72, 1015-1023 (2017).
51. Bernstein, B. E. et al. The NIH Roadmap Epigenomics Mapping Consortium. Nat. Biotechnol. 28, 1045-1048 (2010).
52. Illingworth, R. et al. A novel CpG island set identifies tissue-specific methylation at developmental gene loci. PLoS Biol. 6, e22 (2008).
53. Li, Y. et al. The DNA methylome of human peripheral blood mononuclear cells. PLoS Biol. 8, e1000533 (2010).
54. Thompson, R. F. et al. Tissue-specific dysregulation of DNA methylation in aging. Aging Cell 9, 506-518 (2010).
55. Vidaki, A., Daniel, B., Court, D. S. Forensic DNA methylation profiling-potential opportunities and challenges. Forensic Sci. Int. Genet. 7, 499-507 (2013).
56. Horvath, S. et al. The cerebellum ages slowly according to the epigenetic clock. Aging 7, 294-306 (2015).
57. Sehl, M. E., Henry, J. E., Storniolo, A. M., Ganz, P. A., Horvath, S. DNA methylation age is elevated in breast tissue of healthy women. Breast Cancer Res. Treat. 164, 209-219 (2017).
58. Jenkins, T. G., Aston, K. I., Carrell, D. T. Germ line aging and regional epigenetic instability: Age prediction using human sperm DNA methylation signatures. Preprint at bioRxiv https://doi.org/10.1101/220764 (2017).
59. Levine, M. et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging (US Albany) 2018. Preprint at bioRxiv https://doi.org/10.1101/276162 (2018).
60. 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, 136-144 (2017).
61. 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, 1388-1396 (2015).
62. Levine, M. E., Lu, A. T., Bennett, D. A., Horvath, S. Epigenetic age of the pre-frontal cortex is associated with neuritic plaques, amyloid load, and Alzheimer's disease related cognitive functioning. Aging 7, 1198-1211 (2015).
63. Horvath, S., Ritz, B. R. Increased epigenetic age and granulocyte counts in the blood of Parkinson's disease patients. Aging 7, 1130-1142 (2015).
64. Breitling, L. P. et al. Frailty is associated with the epigenetic clock but not with telomere length in a German cohort. Clin. Epigenet. 8, 21 (2016).
65. Horvath, S. et al. Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring. Aging 7, 1159-1170 (2015).
66. Levine, M. E. et al. DNA methylation age of blood predicts future onset of lung cancer in the women's health initiative. Aging 7, 690-700 (2015).
67. Zheng, Y. et al. Blood epigenetic age may predict cancer incidence and mortality. EBioMedicine 5, 68-73 (2016).
68. Ambatipudi, S. et al. DNA methylome analysis identifies accelerated epigenetic ageing associated with postmenopausal breast cancer susceptibility. Eur. J. Cancer 75, 299-307 (2017).
69. 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, 23237-23245 (2017).
70. Hodgson, K. et al. Epigenetic age acceleration assessed with human white-matter images. J. Neurosci. 37, 4735 (2017).
71. Raina, A. et al. Cerebral white matter hyperintensities on MRI and acceleration of epigenetic aging: The atherosclerosis risk in communities study. Clin. Epigenet. 9, 21 (2017).
72. Degerman, S. et al. Maintained memory in aging is associated with young epigenetic age. Neurobiol. Aging 55, 167-171 (2017).
73. Christiansen, L. et al. DNA methylation age is associated with mortality in a longitudinal Danish twin study. Aging Cell 15, 149-154 (2016).
74. Perna, L. et al. Epigenetic age acceleration predicts cancer, cardiovascular, and all-cause mortality in a German case cohort. Clin. Epigenet. 8, 64 (2016).
75. Dugue, P. A. et al. Association of DNA methylation-based biological age with health risk factors, and overall and cause-specific mortality. Am. J. Epidemiol. https://doi.org/10.1093/aje/kwx291 (2017).
76. Pourquie, O. The segmentation clock: Converting embryonic time into spatial pattern. Science 301, 328-330 (2003).
77. Kruse, K., Jülicher, F. Oscillations in cell biology. Curr. Opin. Cell Biol. 17, 20-26 (2005).
78. Takahashi, J. S. Transcriptional architecture of the mammalian circadian clock. Nat. Rev. Genet. 18, 164-179 (2017).
79. Oh, G. et al. Cytosine modifications exhibit circadian oscillations that are involved in epigenetic diversity and aging. Nat. Commun. 9, 644 (2018).
80. Yin, Y. et al. Impact of cytosine methylation on DNA binding specificities of human transcription factors. Science 356, 2239 (2017).
81. Yu, B. et al. Genome-wide, single-cell DNA methylomics reveals increased non-CpG methylation during human oocyte maturation. Stem Cell Rep. 9, 397-407 (2017).
82. Kelsey, G., Stegle, O., Reik, W. Single-cell epigenomics: Recording the past and predicting the future. Science 358, 69 (2017).
83. Blattler, A., Farnham, P. J. Cross-talk between site-specific transcription factors and DNA methylation states. J. Biol. Chem. 288, 34287-34294 (2013).
84. Yuan, T. et al. An integrative multi-scale analysis of the dynamic DNA methylation landscape in aging. PLoS Genet. 11, e1004996 (2015).
85. Horvath, S. et al. Obesity accelerates epigenetic aging of human liver. Proc. Natl Acad. Sci. USA 111, 15538-15543 (2014).
86. Lu, A. T. et al. Genetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum. Nat. Commun. 7, 10561 (2016).
87. Lu, A. T. et al. Genetic architecture of epigenetic and neuronal ageing rates in human brain regions. Nat. Commun. 8, 15353 (2017).
88. Kananen, L. et al. The trajectory of the blood DNA methylome ageing rate is largely set before adulthood: Evidence from two longitudinal studies. Age 38, 65 (2016).
89. Lu, A. T. et al. GWAS of epigenetic aging rates in blood reveals a critical role for TERT. Nat. Commun. 9, 387 (2018).
90. Mather, K. A., Jorm, A. F., Parslow, R. A., Christensen, H. Is telomere length a biomarker of aging? A review. J. Gerontol. A Biol. Sci. Med. Sci 66A, 202-213 (2011).
91. Sanders, J. L., Newman, A. B. Telomere length in epidemiology: A biomarker of aging, age-related disease, both, or neither? Epidemiol. Rev. 35, 112-131 (2013).
92. Marioni, R. E. et al. The epigenetic clock and telomere length are independently associated with chronological age and mortality. Int. J. Epidemiol. 45, 424-432 (2016).
93. Blackburn, E. H. Telomere states and cell fates. Nature 408, 53-56 (2000).
94. Chen, B. H. et al. Leukocyte telomere length, T cell composition and DNA methylation age. Aging 9, 1983-1995 (2017).
95. Lowe, D., Horvath, S., Raj, K. Epigenetic clock analyses of cellular senescence and ageing. Oncotarget 7, 8524-8531 (2016).
96. Pucci, F., Gardano, L., Harrington, L. Short telomeres in ESCs lead to unstable differentiation. Cell Stem Cell 12, 479-486 (2013).
97. Harrington, L., Pucci, F. In medio stat virtus: Unanticipated consequences of telomere dysequilibrium. Phil. Trans. R. Soc. B Biol Sci. 373, 20160444 (2018).
98. Yang, Z. et al. Correlation of an epigenetic mitotic clock with cancer risk. Genome Biol. 17, 205 (2016).
99. Horvath, S. Erratum to: DNA methylation age of human tissues and cell types. Genome Biol. 16, 96 (2015).
100. Beerman, I. et al. Proliferation-dependent alterations of the DNA methylation landscape underlie hematopoietic stem cell aging. Cell Stem Cell 12, 413-425 (2013).
101. Beerman, I., Rossi, D. J. Epigenetic regulation of hematopoietic stem cell aging. Exp. Cell Res. 329, 192-199 (2014).
102. Issa, J.-P. Aging and epigenetic drift: A vicious cycle. J. Clin. Invest. 124, 24-29 (2014).
103. Collado, M., Blasco, M. A., Serrano, M. Cellular senescence in cancer and aging. Cell 130, 223-233 (2007).
104. Drummond-Barbosa, D. Stem cells, their niches and the systemic environment: An aging network. Genetics 180, 1787-1797 (2008).
105. Melk, A. et al. Effects of donor age and cell senescence on kidney allograft survival. Am. J. Transplant 9, 114-123 (2009).
106. Halloran, P. F., Melk, A., Barth, C. Rethinking chronic allograft nephropathy: The concept of accelerated senescence. J. Am. Soc. Nephrol. 10, 167-181 (1999).
107. Campisi, J. Aging, cellular senescence, and cancer. Annu. Rev. Physiol. 75, 685-705 (2013).
108. Campisi, J., D'Addadi Fagagna, F. Cellular senescence: When bad things happen to good cells. Nat. Rev. Mol. Cell Biol. 8, 729-740 (2007).
109. Coppe, J. P., Desprez, P. Y., Krtolica, A., Campisi, J. The senescence-associated secretory phenotype: The dark side of tumor suppression. Annu. Rev. Pathol. 5, 99-118 (2010).
110. Baker, D. J. et al. Opposing roles for p16Ink4a and p19Arf in senescence and ageing caused by BubR1 insufficiency. Nat. Cell Biol. 10, 825-836 (2008).
111. Chen, H. et al. PDGF signalling controls age-dependent proliferation in pancreatic beta-cells. Nature 478, 349-355 (2011).
112. Berent-Maoz, B., Montecino-Rodriguez, E., Signer, R. A., Dorshkind, K. Fibroblast growth factor-7 partially reverses murine thymocyte progenitor aging by repression of Ink4a. Blood 119, 5715-5721 (2012).
113. Franzen, J. et al. Senescence-associated DNA methylation is stochastically acquired in subpopulations of mesenchymal stem cells. Aging Cell 16, 183-191 (2017).
114. Smith, Z. D., Meissner, A. DNA methylation: Roles in mammalian development. Nat. Rev. Genet. 14, 204-220 (2013).
115. Adams, P. D., Jasper, H., Rudolph, K. L. Aging-induced stem cell mutations as drivers for disease and cancer. Cell Stem Cell 16, 601-612 (2015).
116. Grolleau-Julius, A., Ray, D., Yung, R. L. The role of epigenetics in aging and autoimmunity. Clin. Rev. Allergy Immunol. 39, 42-50 (2010).
117. Neri, F. et al. Intragenic DNA methylation prevents spurious transcription initiation. Nature 543, 72-77 (2017).
118. Jones, P. A., Takai, D. The role of DNA methylation in mammalian epigenetics. Science 293, 1068-1070 (2001).
119. Knight, A. K. et al. An epigenetic clock for gestational age at birth based on blood methylation data. Genome Biol. 17, 206 (2016).
120. Spiers, H. et al. Methylomic trajectories across human fetal brain development. Genome Res. 25, 338-352 (2015).
121. Binder, A. M. et al. Faster ticking rate of the epigenetic clock is associated with faster pubertal development in girls. Epigenetics https://doi.org/10.1080/15592294.2017.1414127 (2018).
122. Bredesen, D. E. The non-existent aging program: How does it work? Aging Cell 3, 255-259 (2004).
123. Skulachev, V. P. Programmed death phenomena: From organelle to organism. Ann. NY Acad. Sci. 959, 214-237 (2002).
124. Mitteldorf, J. Chaotic population dynamics and the evolution of aging: Proposing a demographic theory of senescence. Evol. Ecol. Res. 8, 561-574 (2006).
125. Takasugi, M. Progressive age-dependent DNA methylation changes start before adulthood in mouse tissues. Mech. Ageing Dev. 132, 65-71 (2011).
126. de Magalhaes, J. P. Programmatic features of aging originating in development: Aging mechanisms beyond molecular damage? FASEB J. 26, 4821-4826 (2012).
127. Rando, T. A., Chang, H. Y. Aging, Rejuvenation, and epigenetic reprogramming: Resetting the aging clock. Cell 148, 46-57 (2012).
128. Johnson, A. A. et al. The role of DNA methylation in aging, rejuvenation, and age-related disease. Rejuven. Res. 15, 483-494 (2012).
129. Mitteldorf, J. J. How does the body know how old it is? Introducing the epigenetic clock hypothesis. Biochemistry 78, 1048-1053 (2013).
130. Mitteldorf, J. An epigenetic clock controls aging. Biogerontology 17, 257-265 (2016).
131. Blagosklonny, M. V., Hall, M. N. Growth and aging: A common molecular mechanism. Aging 1, 357-362 (2009).
132. Walker, R. Why we age: Insight into the cause of growing old (Dove Medical Press, 2013).
133. Weidner, C. et al. Epigenetic aging upon allogeneic transplantation: The hematopoietic niche does not affect age-associated DNA methylation. Leukemia 29, 985 (2015).
134. Stolzel, F. et al. Dynamics of epigenetic age following hematopoietic stem cell transplantation. Haematologica 102, e321-e323 (2017).
135. Petkovich, D. A. et al. Using DNA Methylation profiling to evaluate biological age and longevity interventions. Cell Metab. 25, 954-960.e6 (2017).
136. Wang, T. et al. Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment. Genome Biol. 18, 57 (2017).
137. 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, 58 (2017).
138. Stubbs, T. M. et al. Multi-tissue DNA methylation age predictor in mouse. Genome Biol. 18, 68 (2017).
139. Polanowski, A. M., Robbins, J., Chandler, D., Jarman, S. N. Epigenetic estimation of age in humpback whales. Mol. Ecol. Resources 14, 976-987 (2014).
140. Thompson, M. J., Von Holdt, B., Horvath, S., Pellegrini, M. An epigenetic aging clock for dogs and wolves. Aging 9, 1055-1068 (2017).
141. Simpson, V. J., Johnson, T. E., Hammen, R. F. Caenorhabditis elegans DNA does not contain 5-methylcytosine at any time during development or aging. Nucleic Acids Res. 14, 6711-6719 (1986).
142. Newman, A. B. Is the onset of obesity the same as aging? Proc. Natl Acad. Sci. USA 112, E7163-E7163 (2015).
143. Ward-Caviness, C. K. et al. Long-term exposure to air pollution is associated with biological aging. Oncotarget 7, 74510-74525 (2016).
144. Nwanaji-Enwerem, J. C. et al. Long-term ambient particle exposures and blood DNA methylation age: Findings from the VA normative aging study. Environ. Epigenet. 2, 006 (2016).
145. Horvath, S., Levine, A. J. HIV-1 infection accelerates age according to the epigenetic clock. J. Infect. Dis. 212, 1563-1573 (2015).
146. 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, 157-168 (2016).
147. Kananen, L. et al. Cytomegalovirus infection accelerates epigenetic aging. Exp. Gerontol. 72, 227-229 (2015).
148. 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, 1211-1214 (2017).
149. Zannas, A. et al. Lifetime stress accelerates epigenetic aging in an urban, African American cohort: Relevance of glucocorticoid signaling. Genome Biol. 16, 266 (2015).
150. Zannas, A. S. Editorial Perspective: Psychological stress and epigenetic aging-what can we learn and how can we prevent? J. Child Psychol. Psychiatry 57, 674-675 (2016).
151. Dugue, P. A. et al. DNA methylation-based biological aging and cancer risk and survival: Pooled analysis of seven prospective studies. Int. J. Cancer 142, 1611-1619 (2018).
152. Horvath, S. et al. Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels. Aging 8, 1485-1512 (2016).
153. Vidal, L. et al. Specific increase of methylation age in osteoarthritis cartilage. Osteoarthritis Cartilage 24, S63 (2016).