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Clin Epigenetics. 2015 Jul 23;7:72. doi: 10.1186/s13148-015-0109-x. eCollection 2015.

DNA hydroxymethylation age of human blood determined by capillary hydrophilic-interaction liquid chromatography/mass spectrometry.

Clinical epigenetics

Jun Xiong, Han-Peng Jiang, Chun-Yan Peng, Qian-Yun Deng, Meng-Dan Lan, Huan Zeng, Fang Zheng, Yu-Qi Feng, Bi-Feng Yuan

Affiliations

  1. Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of education), Department of Chemistry, Wuhan University, Wuhan, 430072 China.
  2. Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, 430071 China.

PMID: 26207150 PMCID: PMC4511989 DOI: 10.1186/s13148-015-0109-x

Abstract

BACKGROUND: Aging is a complex phenomenon and characterized by a progressive decline in physiology and function of adult tissues. However, it hasn't been well established of the correlation between aging and global DNA methylation and hydroxymethylation that regulate the growth and development of higher organisms.

RESULTS: We developed an on-line trapping/capillary hydrophilic-interaction liquid chromatography/electrospray ionization-mass spectrometry method for ultra-sensitive and simultaneous quantification of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in genomic DNA from human blood. Limits of detection for 5-mC and 5-hmC were 0.04 and 0.13 fmol, respectively. The imprecision and recovery of the method were determined with the relative standard deviations (RSDs) and relative errors being <11.2 and 14.0 %, respectively. We analyzed the contents of 5-mC and 5-hmC in genomic DNA of blood from 238 healthy people aged from 1 to 82 years. The results showed that 5-hmC content was significantly decreased and highly correlated with aging process, while 5-mC only showed slight correlation with age. We then established a DNA hydroxymethylation age model according to 5-hmC content with a mean absolute deviation (MAD) of approximate 8.9 years. We also calculated the mean relative error (MRE) using the predicted ages based on the age model and the chronological ages. The results showed that the MRE was 18.3 % for samples with ages from 20 to 82 years (95 % confidence interval, N = 190).

CONCLUSIONS: The global DNA hydroxymethylation represents a strong and reproducible mark of chronological age, which could be potentially applied in health assessment and prevention of diseases. The identification of biological or environmental factors that influence DNA hydroxymethylation aging rate may permit quantitative assessments of their impacts on health.

Keywords: 5-hydroxymethylcytosine; 5-methylcytosine; Aging; Hydrophilic-interaction liquid chromatography; Mass spectrometry

References

  1. PLoS One. 2011;6(6):e14821 - PubMed
  2. Epigenomics. 2013 Dec;5(6):655-69 - PubMed
  3. Cell. 1999 Jan 22;96(2):291-302 - PubMed
  4. Nat Rev Genet. 2005 Aug;6(8):597-610 - PubMed
  5. Aging Cell. 2010 Aug;9(4):506-18 - PubMed
  6. Curr Alzheimer Res. 2012 Jun;9(5):545-9 - PubMed
  7. Clin Chem. 2013 May;59(5):824-32 - PubMed
  8. Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):10522-7 - PubMed
  9. Genome Biol. 2013;14(10):R115 - PubMed
  10. Sci Rep. 2015 Jan 14;5:7785 - PubMed
  11. Nat Rev Genet. 2013 Mar;14(3):204-20 - PubMed
  12. Nat Biotechnol. 2011 Jan;29(1):68-72 - PubMed
  13. Analyst. 2014 Oct 7;139(19):4940-6 - PubMed
  14. J Biol Chem. 1987 Jul 25;262(21):9948-51 - PubMed
  15. Genes Dev. 2011 Apr 1;25(7):679-84 - PubMed
  16. Nat Neurosci. 2009 Dec;12(12):1559-66 - PubMed
  17. Hum Mol Genet. 2014 Mar 1;23(5):1175-85 - PubMed
  18. Science. 2011 Sep 2;333(6047):1300-3 - PubMed
  19. Angew Chem Int Ed Engl. 2011 Jul 11;50(29):6460-8 - PubMed
  20. Anal Chem. 2005 Jan 15;77(2):504-10 - PubMed
  21. Nat Rev Genet. 2011 Nov 15;13(1):7-13 - PubMed
  22. Anal Chem. 2015 Mar 17;87(6):3445-52 - PubMed
  23. Hepatology. 2015 Aug;62(2):496-504 - PubMed
  24. Genome Res. 2010 Apr;20(4):434-9 - PubMed
  25. Gerontologia. 1973;19(3):138-52 - PubMed
  26. Oncogene. 2013 Jan 31;32(5):663-9 - PubMed
  27. Genome Res. 2010 Mar;20(3):332-40 - PubMed
  28. Nature. 2011 May 19;473(7347):398-402 - PubMed
  29. Science. 2011 Oct 14;334(6053):194 - PubMed
  30. Mol Cell. 2013 Jan 24;49(2):359-67 - PubMed
  31. Chem Soc Rev. 2012 Nov 7;41(21):6916-30 - PubMed
  32. Nature. 2014 Apr 10;508(7495):168-70 - PubMed
  33. Aging Cell. 2010 Feb;9(1):54-63 - PubMed
  34. Nucleic Acids Res. 2013 Jul;41(13):6421-9 - PubMed
  35. Cancer Res. 2011 Dec 15;71(24):7360-5 - PubMed
  36. Ageing Res Rev. 2003 Jul;2(3):245-61 - PubMed
  37. Genome Biol. 2011 Jun 20;12(6):R54 - PubMed
  38. Genome Biol. 2014 Feb 03;15(2):R24 - PubMed
  39. Adv Clin Chem. 2014;67:151-87 - PubMed
  40. J Chromatogr A. 2013 Apr 5;1284:118-25 - PubMed

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