Korean J Leg Med.  2013 Feb;37(1):1-8. 10.7580/kjlm.2013.37.1.1.

DNA Methylation-Based Age Estimation in the Forensic Field

• An JH
• Shin KJ
• Choi A
• Yang WI
• Lee HY

• KMID: 2250272
• DOI: http://doi.org/10.7580/kjlm.2013.37.1.1

Abstract

The estimation of age is an important issue in forensic science, and the forensic community has attempted many times to establish methods for solving this issue. Aging leads to alterations in tissues and organs at the molecular level. These alterations at the molecular level may aid forensic scientists to estimate the age of a living person or a dead body. Initially, the focus was on the genetic components of aging, but recently, epigenetic mechanisms have emerged as the key contributors to the alterations in genome structure and function that accompany aging. In particular, DNA methylation is one of the best-understood mechanisms, and it has been suggested as a promising biomarker for age estimation in many studies. In this review, we summarize the recent studies on age-associated DNA methylation changes in different tissues and discuss its possible and practical applications in forensics.

Keyword

DNA methylation; Age estimation; Epigenetics; Forensics

MeSH Terms

Aging
DNA
DNA Methylation
Epigenomics
Forensic Sciences
Genome
Humans
DNA

Reference

1. Kayser M, de Knijff P. Improving human forensics through advances in genetics, genomics and molecular biology. Nat Rev Genet. 2011; 12:179–92.

2. Kayser M, Schneider PM. DNA-based prediction of human externally visible characteristics in forensics: motivations, scientific challenges, and ethical considerations. Forensic Sci Int Genet. 2009; 3:154–61.

3. Ohtani S. Estimation of age from dentin by using the racemization reaction of aspartic acid. Am J Forensic Med Pathol. 1995; 16:158–61.

4. Sato Y, Kondo T, Ohshima T. Estimation of age of human cadavers by immunohistochemical assessment of ad-vanced glycation end products in the hippocampus. Histopathology. 2001; 38:217–20.

5. Harley C, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature. 1990; 345:458–60.

6. Tsuji A, Ishiko A, Takasaki T, et al. Estimating age of humans based on telomere shortening. Forensic Sci Int. 2002; 126:197–9.

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

8. Zubakov D, Liu F, van Zelm MC, et al. Estimating human age from T-cell DNA rearrangements. Curr Biol. 2010; 20:970–1.

9. Russo VEA, Martienssen RA, Riggas AD. Epigenetic mechanisms of gene regulation. New York: Cold Spring Harbor Laboratory Press;1996.

10. Gonzalo S. Epigenetic alterations in aging. J Appl Physiol. 2010; 109:586–97.

11. Miranda TB, Jones PA. DNA methylation: the nuts and bolts of repression. J Cell Physiol. 2007; 213:384–90.

12. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002; 16:6–21.

13. Wilson VL, Smith RA, Ma S, et al. Genomic 5-methyldeoxycytidine decreases with age. J Biol Chem. 1987; 262:9948–51.

14. Vanyushin BF, Nemirovsky LE, Klimenko VV, et al. The 5-methylcytosine in DNA of rats. Tissue and age specificity and the changes induced by hydrocortisone and other agents. Gerontologia. 1973; 19:138–52.

15. Fuke C, Shimabukuro M, Petronis A, et al. Age related changes in 5-methylcytosine content in human peripheral leukocytes and placentas: an HPLC-based study. Ann Hum Genet. 2004; 68:196–204.

16. Casillas MA Jr, Lopatina N, Andrews LG, et al. Transcriptional control of the DNA methyltransferases is altered in aging and neoplastically-transformed human fibroblasts. Mol Cell Biochem. 2003; 252:33–43.

17. Murgatroyd C, Wu Y, Bockmuhl Y, et al. The Janus face of DNA methylation in aging. Aging. 2010; 2:107–10.

18. Rakyan VK, Down TA, Maslau S, et al. Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains. Genome Res. 2010; 20:434–9.

19. Bocklandt S, Lin W, Sehl ME, et al. Epigenetic predictor of age. PLoS ONE. 2011; 6:e14821.

20. Koch CM, Suschek CV, Lin Q, et al. Specific Age-associated DNA methylation changes in human dermal fibroblasts. PLoS ONE. 2011; 6:e16679.

21. Gronniger E, Weber B, Heil O, et al. Aging and chronic sun exposure cause distinct epigenetic changes in human skin. PLoS Genet. 2010; 6:e1000971.

22. Bocker MT, Hellwig I, Breiling A, et al. Genomewide promoter DNA methylation dynamics of human hematopoietic progenitor cells during differentiation and aging. Blood. 2011; 117:e182–9.

23. Teschendorff AE, Menon U, Gentry-Maharaj A, et al. Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer. Genome Res. 2010; 20:440–6.

24. Koch C, Wagner W. Epigenetic-aging-signature to determine age in different tissues. Aging. 2011; 3:1018–27.

25. Bell JT, Tsai PC, Yang TP, et al. Epigenomewide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population. PLoS Genet. 2012; 8:e1002629.

26. Simm A, Nass N, Bartling B, et al. Potential biomarkers of ageing. Biol Chem. 2008; 389:257–65.

27. Dedeurwaerder S, Defrance M, Calonne E, et al. Evaluation of the infinium methylation 450K technology.

28. Garagnani P, Bacalini MG, Pirazzini C, et al. Methylation of ELOVL2 gene as a new epigenetic marker of age. Aging Cell. 2012; 11:1132–4.

29. Hannum G, Ginney J, Zhao L, et al. Genomewide methylation profiles reveal quantitative views of human aging rates. Mol Cell. 2013; 49:359–67.

30. Zou H, Hastie T. Regularization and variable selection via the elastic net. J R Statist Soc B. 2005; 67:301–20.

31. Heyn H, Li N, Ferreira HJ, et al. Distinct DNA methy-lomes of newborns and centenarians. Proc Natl Acad Sci USA. 2012; 109:10522–7.

32. Bibikova M, Le J, Barnes B, et al. Genomewide DNA methylation profiling using Infinium^� assay. Epigenomics. 2009; 1:177–200.

33. Shames DS, Minna JD, Gazdar AF. Methods for detecting DNA methylation in tumors: from bench to bedside. Cancer Lett. 2007; 251:187–98.

34. Frommer M, McDonald LE, Millar DS, et al. A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc Natl Acad Sci U S A. 1992; 89:1827–31.

35. Zhang Y, Rohde C, Tierling S, et al. DNA methylation analysis by bisulfite conversion, cloning, and sequencing of individual clones. Methods Mol Biol. 2009; 507:177–87.

36. van den Boom D, Ehrich M. Mass spectrometric analysis of cytosine methylation by base-specific cleavage and primer extension methods. Methods Mol Biol. 2009; 507:207–27.

37. Dejeux E, El abdalaoui H, Gut IG, et al. Identification and quantification of differentially methylated loci by the pyrosequencing technology. Methods Mol Biol. 2009; 507:189–205.

38. Licchesi JD, Herman JG. Methylation-specific PCR. Methods Mol Biol. 2009; 507:305–23.

39. Brena RM, Plass C. Bio-COBRA: absolute quantification of DNA methylation in electrofluidics chips. Methods Mol Biol. 2009; 507:257–69.

40. Kaminsky Z, Petronis A. Methylation SNaPshot: a method for the quantification of site-specific DNA methylation levels. Methods Mol Biol. 2009; 507:241–55.

41. Oakes CC, La Salle S, Trasler JM, et al. Restriction digestion and real-time PCR (qAMP). Methods Mol Biol. 2009; 507:271–80.

42. Frumkin D, Wasserstrom A, Budowle B, et al. DNA methylation-based forensic tissue identification. Forensic Sci Int Genet. 2011; 5:517–24.

43. Lee HY, Park MJ, Choi A, et al. Potential forensic application of DNA methylation profiling to body fluid identification. Int J Legal Med. 2012; 126:55–62.

44. Kayser M, Liu F, Janssens AC, et al. Three genomewide association studies and a linkage analysis identify HERC2 as a human iris color gene. Am J Hum Genet. 2008; 82:411–23.

45. Liu F, Wollstein A, Hysi PG, et al. Digital quantification of human eye color highlights genetic association of three new loci. PLoS Genet. 2010; 6:e1000934.

46. Branicki W, Brudnik U, Kupiec T, et al. Determination of phenotype associated SNPs in the MC1R gene. J Forensic Sci. 2007; 52:349–54.