Abstract
DNA methylation of the elongation of very long chain fatty acids protein 2 (ELOVL2) was suggested as a biomarker of biological aging, while childhood maltreatment (CM) has been associated with accelerated biological aging. We investigated the association of age and CM experiences with ELOVL2 methylation in peripheral blood mononuclear cells (PBMC). Furthermore, we investigated ELOVL2 methylation in the umbilical cord blood mononuclear cells (UBMC) of newborns of mothers with and without CM. PBMC and UBMC were isolated from 113 mother-newborn dyads and genomic DNA was extracted. Mothers with and without CM experiences were recruited directly postpartum. Mass array spectrometry and pyrosequencing were used for methylation analyses of ELOVL2 intron 1, and exon 1 and 5' end, respectively. ELOVL2 5' end and intron 1 methylation increased with higher age but were not associated with CM experiences. On the contrary, overall ELOVL2 exon 1 methylation increased with higher CM, but these changes were minimal and did not increase with age. Maternal CM experiences and neonatal methylation of ELOVL2 intron 1 or exon 1 were not significantly correlated. Our study suggests region-specific effects of chronological age and experienced CM on ELOVL2 methylation and shows that the epigenetic biomarker for age within the ELOVL2 gene does not show accelerated biological aging years after CM exposure.
Highlights
The biological age of an organism can be estimated based on endocrine, immunological, or molecular observations (Jin, 2010)
We conducted explorative analyses of DNA methylation (DNAm) in an extended area of the ELOVL2 gene: we examined the DNAm within exon 1, which is located within the CpG island of the ELOVL2 gene promoter and encompasses one transcription start site (TSS), and intron 1, which extends from the downstream region into the 3′ shore of the CpG island (Figure 1)
We found that, in peripheral blood mononuclear cells (PBMC), the ELOVL2 5′ end did not show increased methylation in association with childhood maltreatment (CM). We extended these associations between age and DNAm to the intron 1 region of the ELOVL2 gene
Summary
The biological age of an organism can be estimated based on endocrine, immunological, or molecular observations (Jin, 2010). One possible explanation for this association is the allostatic load that impacts the immune system: chronic or repeated exposure to stress, especially during critical stress-sensitive developmental stages, could constantly trigger the activation of the immune system. This may result in elevated levels of inflammation as well as accelerated aging processes Alterations of mitochondrial biogenesis (Tyrka et al, 2010, 2016), which are important in cellular aging, apoptosis, and higher levels of reactive oxygen species were found in association with CM (Boeck et al, 2016)
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