Age prediction in living: Forensic epigenetic age estimation based on blood samples

A Blood–Bone–Tooth Model for Age Prediction in Forensic Contexts

“…A total of 185 samples (76 females, 109 males; aged 1–94 years old) from living and deceased individuals from blood, bones and teeth previously addressed for DNAm levels by Sanger sequencing in genes ELOVL2 (9 CpGs), EDARADD (4 CpGs), FHL2 (12 CpGs), PDE4C (12 CpGs) and C1orf132 (6 CpGs) [ 5 , 6 , 8 ], and 168 samples (67 females, 101 males; 1–94 aged years old) from living and deceased individuals previously analyzed using a SNaPshot assay for 5 specific CpG sites in genes ELOVL2, FHL2, KLF14 , C1orf132 and TRIM59 [ 7 , 8 ], were considered for this study. The same samples were addressed in both methodologies; however, some samples failed PCR amplification and were excluded from further analysis, which explains the difference in number between the two methods.…”

“…Our group previously assessed the methylation information of age-correlated CpG sites in genes ELOVL2 , FHL2 , EDARADD , PDE4C , C1orf132 , TRIM59 and KLF14, captured by Sanger sequencing and SNaPshot methodologies [ 5 , 6 , 7 , 8 ]. Several tissue-specific APMs were developed, including for blood [ 5 , 6 , 7 ], teeth [ 8 ] and bones [ 8 ].…”

“…Our group previously assessed the methylation information of age-correlated CpG sites in genes ELOVL2 , FHL2 , EDARADD , PDE4C , C1orf132 , TRIM59 and KLF14, captured by Sanger sequencing and SNaPshot methodologies [ 5 , 6 , 7 , 8 ]. Several tissue-specific APMs were developed, including for blood [ 5 , 6 , 7 ], teeth [ 8 ] and bones [ 8 ]. Considering the scarcity of multi-tissue APMs developed until now, the present study aimed to re-examine the obtained DNAm levels for these highly age-correlated genes combining the previously addressed tissues to test for a multi-tissue blood–bone–tooth age prediction model (BBT-APM).…”

How (Epi)Genetic Regulation of the LIM-Domain Protein FHL2 Impacts Multifactorial Disease

“…In 2013, Hannum et al developed a mathematical model for age prediction based on methylation of 71 CpG sites in different genes, and since then efforts have been made to simplify and refine this biological age prediction tool [77]. One of the hyper-methylated loci most consistently found upon aging is located in the FHL2 gene, together with loci in Elongation of Very Long Chain Fatty Acids Protein 2 (ELOVL2), Kruppel-like factor 14 (KLF14) and Proenkephalin (PENK) [43,[78][79][80]. More specifically, there is a region of clustered CpG sites (a CpG island) located proximal to the first exon of the FHL2 gene (Figure 4).…”

“…Recently, forensic studies have expanded the use of the age-prediction tool to other samples apart from blood, such as saliva, bone or buccal swabs, and also confirmed its use in living and deceased individuals. In all of the samples except buccal swabs, at least one of the aforementioned three CpG sites for FHL2 is consistently used as part of the array of CpG sites used for age determination [79,[82][83][84][85][86][87]. Even though a study performed in bone alone did not find a significant correlation of age to FHL2 methylation sites [25], in teeth, the methylation of 8 CpG sites in FHL2, together with sites in ELOVL2 and PENK, can accurately predict age [88].…”