Skip to main content

Advertisement

SpringerLink
Log in

Age-related DNA methylation changes for forensic age-prediction

  • Original Article
  • Published:
International Journal of Legal Medicine Aims and scope Submit manuscript

Abstract

There is no available method of age-prediction for biological samples. The accumulating evidences indicate that DNA methylation patterns change with age. Aging resembles a developmentally regulated process that is tightly controlled by specific epigenetic modifications and age-associated methylation changes exist in human genome. In this study, three age-related methylation fragments were isolated and identified in blood of 40 donors. Age-related methylation changes with each fragment was validated and replicated in a general population sample of 65 donors over a wide age range (11–72 years). Methylation of these fragments is linearly correlated with age over a range of six decades (r = 0.80–0.88). Using average methylation of CpG sites of three fragments, a regression model that explained 95 % of the variance in age was built and is able to predict an individual’s age with great accuracy (R 2 = 0.93). The predicted value is highly correlated with the observed age in the sample (r = 0.96) and has great accuracy of average 4 years difference between predicted age and true age. This study implicates that DNA methylation can be an available biological marker of age-prediction. Further measurement of relevant markers in the genome could be a tool in routine screening to predict age of forensic biological samples.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Hillewig E, Degroote J, Van der Paelt T, Visscher A, Vandemaele P, Lutin B, D’Hooghe L, Vandriessche V, Piette M, Verstraete K (2013) Magnetic resonance imaging of the sternal extremity of the clavicle in forensic age estimation: towards more sound age estimates. Int J Legal Med 127:677–689

    Article  CAS  PubMed  Google Scholar 

  2. Thevissen PW, Kaur J, Willems G (2012) Human age estimation combining third molar and skeletal development. Int J Legal Med 126:285–292

    Article  CAS  PubMed  Google Scholar 

  3. Saeed M, Berlin RM, Cruz TD (2012) Exploring the utility of genetic markers for predicting biological age. Leg Med (Tokyo) 14:279–285

    Article  CAS  Google Scholar 

  4. Barrett EL, Burke TA, Hammers M, Komdeur J, Richardson DS (2013) Telomere length and dynamics predict mortality in a wild longitudinal study. Mol Ecol 22:249–259

    Article  PubMed  Google Scholar 

  5. Slijepcevic P (2008) DNA damage response, telomere maintenance and ageing in light of the integrative model. Mech Ageing Dev 129:11–16

    Article  CAS  PubMed  Google Scholar 

  6. Meissner C, Ritz-Timme S (2010) Molecular pathology and age estimation. Forensic Sci Int 203:34–43

    Article  CAS  PubMed  Google Scholar 

  7. Meissner C, Bruse P, Mohamed SA, Schulz A, Warnk H, Storm T, Oehmichen M (2008) The 4977 bp deletion of mitochondrial DNA in human skeletal muscle, heart and different areas of the brain: a useful biomarker or more? Exp Gerontol 43:645–652

    Article  CAS  PubMed  Google Scholar 

  8. Pilin A, Pudil F, Bencko V (2007) Changes in colour of different human tissues as a marker of age. Int J Legal Med 121:158–162

    Article  PubMed  Google Scholar 

  9. Othani S, Abe I, Yamamoto T (2005) An application of d- and l-aspartic acid mixtures as standard specimens for the chronological age estimation. J Forensic Sci 50:1298–1302

    Google Scholar 

  10. Zubakov D, Liu F, van Zelm MC, Vermeulen J, Oostra BA, van Duijn CM, Driessen GJ, van Dongen JJ, Kayser M, Langerak AW (2010) Estimating human age from T-cell DNA rearrangements. Curr Biol 20:R970–R971

    Article  CAS  PubMed  Google Scholar 

  11. Kayser M, Knijff P (2011) Improving human forensics through advances in genetics, genomics and molecular biology. Genetics 12:179–192

    CAS  PubMed  Google Scholar 

  12. Ou XL, Gao J, Wang H, Wang HS, Lu HL, Sun HY (2012) Predicting human age with bloodstains by sjTREC quantification. PLoS One 7:e42412

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Schellenberg A, Lin Q, Schüler H, Koch CM, Joussen S, Denecke B, Walenda G, Pallua N, Suschek CV, Zenke M, Wagner W (2011) Replicative senescence of mesenchymal stem cells causes DNA-methylation changes which correlate with repressive histone marks. Aging (Albany NY) 3:873–888

    CAS  Google Scholar 

  14. Fraga MF, Esteller M (2007) Epigenetics and aging: the targets and the marks. Trends Genet 23:413–418

    Article  CAS  PubMed  Google Scholar 

  15. Murgatroyd C, Wu Y, Bockmühl Y, Spengler D (2010) The Janus face of DNA methylation in aging. Aging (Albany NY) 2:107–110

    CAS  Google Scholar 

  16. Martino DJ, Tulic MK, Gordon L, Hodder M, Richman T, Metcalfe J, Prescott SL, Saffery R (2011) Evidence for age-related and individual-specific changes in DNA methylation profile of mononuclear cells during early immune development in humans. Epigenetics 6:1085–1094

    Article  CAS  PubMed  Google Scholar 

  17. Jones PA, Takai D (2001) The role of DNA methylation in mammalian epigenetics. Science 293:1068–1070

    Article  CAS  PubMed  Google Scholar 

  18. Fraga MF, Agrelo R, Esteller M (2007) Cross-talk between aging and cancer: the epigenetic language. Ann N Y Acad Sci 1100:60–74

    Article  CAS  PubMed  Google Scholar 

  19. Ben-Avraham D, Muzumdar RH, Atzmon G (2012) Epigenetic genome-wide association methylation in aging and longevity. Epigenomics 4:503–509

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Leeb M, Wutz A (2012) Establishment of epigenetic patterns in development. Chromosoma 121:251–262

    Article  PubMed Central  PubMed  Google Scholar 

  21. Fuke C, Shimabukuro M, Petronis A, Sugimoto J, Oda T, Miura K, Miyazaki T, Ogura C, Okazaki Y, Jinno Y (2004) Age related changes in 5-methylcytosine content in human peripheral leukocytes and placentas: an HPLC-based study. Ann Hum Genet 68:196–204

    Article  CAS  PubMed  Google Scholar 

  22. Casillas MAJ, Lopatina N, Andrews LG, Tollefsbol TO (2003) Transcriptional control of the DNA methyltransferases is altered in aging and neoplastically-transformed human fibroblasts. Mol Cell Biochem 252:33–43

    Article  CAS  PubMed  Google Scholar 

  23. Shi X, Li J, Zhao C, Lv S, Xu G (2006) Methylation analysis of hMLH1 gene promoter by a bisulfite-sensitive single-strand conformation polymorphism-capillary electrophoresis method. Biomed Chromatogr 20:815–820

    Article  CAS  PubMed  Google Scholar 

  24. So K, Tamura G, Honda T, Homma N, Waki T, Togawa N, Nishizuka S, Motoyama T (2006) Multiple tumor suppressor genes are increasingly methylated with age in non-neoplastic gastric epithelia. Cancer Sci 97:1155–1158

    Article  CAS  PubMed  Google Scholar 

  25. Rakyan VK, Down TA, Maslau S, Andrew T, Yang TP, Beyan H, Whittaker P, McCann OT, Finer S, Valdes AM, Leslie RD, Deloukas P, Spector TD (2010) Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains. Genome Res 20:434–439

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Teschendorff AE, Menon U, Gentry-Maharaj A, Ramus SJ, Weisenberger DJ, Shen H, Campan M, Noushmehr H, Bell CG, Maxwell AP, Savage DA, Mueller-Holzner E, Marth C, Kocjan G, Gayther SA, Jones A, Beck S, Wagner W, Laird PW, Jacobs IJ, Widschwendter M (2010) Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer. Genome Res 20:440–446

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Koch CM, Suschek CV, Lin Q, Bork S, Goergens M, Joussen S, Pallua N, Ho AD, Zenke M, Wagner W (2011) Specific age-associated DNA methylation changes in human dermal fibroblasts. PLoS One 6:e16679

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Bocklandt S, Lin W, Sehl ME, Sánchez FJ, Sinsheimer JS, Horvath S, Vilain E (2011) Epigenetic predictor of age. PLoS One 6:e14821

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Koch CM, Wagner W (2011) Epigenetic-aging-signature to determine age in different tissues. Aging (Albany NY) 3:1018–1027

    CAS  Google Scholar 

  30. Hannum G, Guinney J, Zhao L, Zhang L, Hughes G, Sadda S, Klotzle B, Bibikova M, Fan JB, Gao Y, Deconde R, Chen M, Rajapakse I, Friend S, Ideker T, Zhang K (2013) Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell 49:359–367

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Yi SH, Mei K, Xu LC, Huang DX, Yang RZ (2014) Isolation and identification of age-related DNA methylation markers for forensic age-prediction. Forensic Sci Int Genet 11:117–125

    Article  CAS  PubMed  Google Scholar 

  32. Ehrich M, Nelson MR, Stanssens P, Zabeau M, Liloglou T, Xinarianos G, Cantor CR, Field JK, Boom D (2005) Quantitative high-throughput analysis of DNA methylation patterns by base-specific cleavage and mass spectrometry. Proc Natl Acad Sci U S A 102:15785–15790

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Coolen MW, Statham AL, Gardiner-Garden M, Clark SJ (2007) Genomic profiling of CpG methylation and allelic specificity using quantitative high-throughput mass spectrometry: critical evaluation and improvements. Nucleic Acids Res 35:e119

    Article  PubMed Central  PubMed  Google Scholar 

  34. Wojdacz TK, Hansen LL (2006) Techniques used in studies of age-related DNA methylation changes. Ann N Y Acad Sci 1067:479–487

    Article  CAS  PubMed  Google Scholar 

  35. Kaneda A, Takai D, Kaminishi M, Okochi E, Ushijima T (2003) Methylation-sensitive representational difference analysis and its application to cancer research. Ann NY Acad Sci 983:131–141

    Article  CAS  PubMed  Google Scholar 

  36. Song F, Mahmood S, Ghosh S, Liang P, Smiraglia DJ, Nagase H, Held WA (2009) Tissue specific differentially methylated regions (TDMR): changes in DNA methylation during development. Genomics 93:130–139

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Ma LL, Yi SH, Huang DX, Mei K, Yang RZ (2013) Screening and identification of tissue-specific methylation for body fluid identification. Forensic Sci Int Genet SS 4:e37–e38

    Article  Google Scholar 

Download references

Acknowledgments

This research was supported by the National Natural Science Foundation of China (Nos. 30772291, 81373250, and 81202386), the Natural Science Foundation of Hubei Province (No. 2010CDB03201), and the Fundamental Research Funds for the Central Universities, HUST: Nos. 2011JC050 and 2013TS111.

Author information

Authors and Affiliations

  1. Department of Forensic Medicine of Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China

    Shao Hua Yi, Yun Shu Jia, Kun Mei, Rong Zhi Yang & Dai Xin Huang

Authors
  1. Shao Hua Yi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yun Shu Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kun Mei
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rong Zhi Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dai Xin Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dai Xin Huang.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOC 29 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yi, S.H., Jia, Y.S., Mei, K. et al. Age-related DNA methylation changes for forensic age-prediction. Int J Legal Med 129, 237–244 (2015). https://doi.org/10.1007/s00414-014-1100-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00414-014-1100-3

Keywords

Search

Navigation