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Yan Q, Paul KC, Lu AT, et al. Epigenetic mutation load is weakly correlated with epigenetic age acceleration. Aging (Albany NY). 2020;12(18):17863-17894doi: 10.18632/aging.103950.
Yan, Q., Paul, K. C., Lu, A. T., Kusters, C., Binder, A. M., Horvath, S., & Ritz, B. (2020). Epigenetic mutation load is weakly correlated with epigenetic age acceleration. Aging, 12(18), 17863-17894. https://doi.org/10.18632/aging.103950
Yan, Qi, et al. "Epigenetic mutation load is weakly correlated with epigenetic age acceleration." Aging vol. 12,18 (2020): 17863-17894. doi: https://doi.org/10.18632/aging.103950
Yan Q, Paul KC, Lu AT, Kusters C, Binder AM, Horvath S, Ritz B. Epigenetic mutation load is weakly correlated with epigenetic age acceleration. Aging (Albany NY). 2020 Sep 29;12(18):17863-17894. doi: 10.18632/aging.103950. Epub 2020 Sep 29. PMID: 32991324; PMCID: PMC7585066.
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Aging (Albany NY). 2020 Sep 29;12(18):17863-17894. doi: 10.18632/aging.103950. Epub 2020 Sep 29.

Epigenetic mutation load is weakly correlated with epigenetic age acceleration.

Aging

Qi Yan, Kimberly C Paul, Ake T Lu, Cynthia Kusters, Alexandra M Binder, Steve Horvath, Beate Ritz

Affiliations

  1. Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA 90095, USA.
  2. Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
  3. Population Sciences in the Pacific Program (Cancer Epidemiology), University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI 96813, USA.
  4. Department of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA.
  5. Department of Neurology, UCLA School of Medicine, Los Angeles, CA 90095, USA.

PMID: 32991324 PMCID: PMC7585066 DOI: 10.18632/aging.103950

Abstract

DNA methylation (DNAm) age estimators are widely used to study aging-related conditions. It is not yet known whether DNAm age is associated with the accumulation of stochastic epigenetic mutations (SEMs), which reflect dysfunctions of the epigenetic maintenance system. Here, we defined epigenetic mutation load (EML) as the total number of SEMs per individual. We assessed associations between EML and DNAm age acceleration estimators using biweight midcorrelations in four population-based studies (total n = 6,388). EML was not only positively associated with chronological age (meta r = 0.171), but also with four measures of epigenetic age acceleration: the Horvath pan tissue clock, intrinsic epigenetic age acceleration, the Hannum clock, and the GrimAge clock (meta-analysis correlation ranging from r = 0.109 to 0.179). We further conducted pathway enrichment analyses for each participant's SEMs. The enrichment result demonstrated the stochasticity of epigenetic mutations, meanwhile implicated several pathways: signaling, neurogenesis, neurotransmitter, glucocorticoid, and circadian rhythm pathways may contribute to faster DNAm age acceleration. Finally, investigating genomic-region specific EML, we found that EMLs located within regions of transcriptional repression (TSS1500, TSS200, and 1stExon) were associated with faster age acceleration. Overall, our findings suggest a role for the accumulation of epigenetic mutations in the aging process.

Keywords: DNA methylation; aging; epigenetic clock; epigenetic mutation load; stochastic epigenetic mutation

References

  1. Aging (Albany NY). 2018 Apr 18;10(4):573-591 - PubMed
  2. Aging (Albany NY). 2015 Dec;7(12):1198-211 - PubMed
  3. Genome Biol. 2014 Feb 03;15(2):R24 - PubMed
  4. Aging Cell. 2012 Aug;11(4):694-703 - PubMed
  5. Genome Biol. 2016 Aug 11;17(1):171 - PubMed
  6. J Stat Softw. 2012 Mar;46(11): - PubMed
  7. Clin Epigenetics. 2018 Jun 8;10:77 - PubMed
  8. J Infect Dis. 2015 Nov 15;212(10):1563-73 - PubMed
  9. Epigenetics. 2019 Oct;14(10):1003-1018 - PubMed
  10. Aging Cell. 2015 Jun;14(3):491-5 - PubMed
  11. Aging Cell. 2012 Dec;11(6):1132-4 - PubMed
  12. Front Genet. 2016 Jul 14;7:126 - PubMed
  13. BMC Bioinformatics. 2012 May 08;13:86 - PubMed
  14. Nucleic Acids Res. 2016 Feb 18;44(3):e20 - PubMed
  15. Nat Rev Genet. 2018 Jun;19(6):371-384 - PubMed
  16. Bioinformatics. 2014 May 15;30(10):1363-9 - PubMed
  17. Clin Epigenetics. 2019 Dec 9;11(1):187 - PubMed
  18. Cell. 2013 Jun 6;153(6):1194-217 - PubMed
  19. Aging (Albany NY). 2017 Apr;9(4):1143-1152 - PubMed
  20. Aging (Albany NY). 2015 Sep;7(9):690-700 - PubMed
  21. Epigenomics. 2016 May;8(5):705-19 - PubMed
  22. Oncotarget. 2017 Jun 27;8(26):41890-41902 - PubMed
  23. Cell. 2014 Nov 6;159(4):709-13 - PubMed
  24. Control Clin Trials. 1998 Feb;19(1):61-109 - PubMed
  25. EBioMedicine. 2017 Jul;21:29-36 - PubMed
  26. OMICS. 2012 May;16(5):284-7 - PubMed
  27. Int J Epidemiol. 2015 Aug;44(4):1388-96 - PubMed
  28. Mol Cell. 2013 Jan 24;49(2):359-367 - PubMed
  29. Epigenetics. 2018;13(9):975-987 - PubMed
  30. Hum Mol Genet. 2016 Jan 1;25(1):123-9 - PubMed
  31. Lancet Diabetes Endocrinol. 2018 Sep;6(9):743-752 - PubMed
  32. Nucleic Acids Res. 2013 Apr;41(7):e90 - PubMed
  33. Nat Rev Mol Cell Biol. 2007 Sep;8(9):692-702 - PubMed
  34. Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10604-9 - PubMed
  35. Aging (Albany NY). 2017 Feb 14;9(2):419-446 - PubMed
  36. Ethn Dis. 2005 Autumn;15(4 Suppl 6):S6-4-17 - PubMed
  37. Nat Commun. 2014 Jun 10;5:4082 - PubMed
  38. Aging (Albany NY). 2016 Sep 28;8(9):1844-1865 - PubMed
  39. Aging (Albany NY). 2015 Aug;7(8):568-78 - PubMed
  40. Aging (Albany NY). 2019 Jan 21;11(2):303-327 - PubMed
  41. Nat Commun. 2017 Mar 17;8:14617 - PubMed
  42. Ann Epidemiol. 2003 Oct;13(9 Suppl):S5-17 - PubMed
  43. Genome Biol. 2014 Dec 03;15(12):503 - PubMed
  44. Aging (Albany NY). 2015 Dec;7(12):1130-42 - PubMed
  45. Genome Biol. 2019 Nov 25;20(1):249 - PubMed
  46. Am J Public Health Nations Health. 1951 Mar;41(3):279-81 - PubMed
  47. Aging (Albany NY). 2019 Aug 18;11(16):5895-5923 - PubMed
  48. Bioinformatics. 2017 Feb 15;33(4):558-560 - PubMed
  49. Aging (Albany NY). 2018 Jul 26;10(7):1758-1775 - PubMed
  50. Mol Cell. 2018 Sep 20;71(6):882-895 - PubMed
  51. Genome Biol. 2016 Sep 22;17(1):191 - PubMed
  52. Ann N Y Acad Sci. 2000 Jun;908:244-54 - PubMed
  53. Genome Biol. 2013;14(10):R115 - PubMed
  54. PLoS One. 2011 Jan 18;6(1):e14524 - PubMed
  55. Bioinformatics. 2014 Aug 15;30(16):2360-6 - PubMed
  56. Genome Biol. 2015 Dec 17;16:266 - PubMed
  57. Aging (Albany NY). 2019 Apr 14;11(7):2045-2070 - PubMed
  58. Cell Rep. 2016 Nov 15;17(8):2137-2150 - PubMed
  59. Genome Med. 2014 Mar 25;6(3):23 - PubMed
  60. Clin Epigenetics. 2020 Mar 26;12(1):49 - PubMed

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