Associations between Global DNA Methylation and Telomere Length in Healthy Adolescents

Abstract

Emerging evidence suggests that epigenetics regulates telomere dynamics in adults. However, the relationship between these pathways in children and youth remains unknown. Thus, we examined this association in 542 healthy adolescents aged 14 to 18 years old (44.8% African Americans; 55.2% females). Global DNA methylation level (%5-mC) was quantified using ELISA method. Leukocyte telomere length (LTL) was defined as relative telomere to single copy gene (T/S) ratio. Multiple linear regression models, adjusted for age, gender, ethnicity, Tanner stage, BMI, PA, and batch effect, revealed that %5 mC was associated with LTL (adjusted β = 0.17, p < 0.01). %5 mC accounted for 5.0% of the variation for LTL. A significant gender interaction was identified (p < 0.01). There was an association between %5 mC and LTL in females (all ps < 0.01), but not in males. Further sensitivity analyses by race revealed similar associations in African Americans and whites (all ps < 0.03). The present study, for the first time, shows that lower levels of global DNA methylation are associated with shorter telomere lengths in youth, which may decrease genome stability and augment the susceptibility to diseases. Longitudinal studies are warranted to establish the effects of global DNA methylation on LTL maintenance over time.

Leukocyte telomere length and epigenetic-based mortality risk score: associations with all-cause mortality among older adults

“…TL has been found to be associated with epigenetic alterations across different populations and environmental exposures [22][23][24]. TL was not only associated with the global methylations among young adults [23], but also associated with specific DNA methylation changes in response to gestational age among placental samples and in response to smoking exposure among older adults [22,24], respectively. Given that, we hypothesized that TL might be associated with the MS and hence the MS might be able to reflect the aging process which the TL is involved in.…”

Research Review: Intergenerational transmission of disadvantage: epigenetics and parents' childhoods as the first exposure

“…In this review, we describe a new hypothesized factor in this intergenerational transmission process: epigenetics – molecular processes that change the expression of genes independent of changing DNA sequence. Epigenetic marks have been observed in genes thought to impact stress response (Edelman et al., ; de Rooij et al., ), emotion regulation (Puglia, Lillard, Morris, & Connelly, ), disease susceptibility (Dong, Huang, Gutin, Dong, & Zhu, ), and mental disorders (Dammann et al., ; Melas et al., ; Na et al., ; Wang, Feng, et al., ); all factors that can lead to compromised life courses. While more research is needed to clarify the role of epigenetics in phenotypic expression in these areas, epigenetic intergenerational transmission could potentially be a biological component of the reproduction of poverty across generations…”

Genetic and Epigenetic Regulation of Telomere Length: Current Findings, Methodological Limitations and Possibilities for Future Studies

“…Although the sample size was limited, this exploratory study suggests global DNA hypomethylation may be related to decreased TL in peripheral blood leukocytes. A recent larger study using an ELISA-based method to determine global 5mC content also showed that decreased global DNA methylation was associated with shortened TL in adolescents [71]. Taken together these studies provide the impetus for future studies, involving larger cohorts, to focus on gene-specific DNA methylation signatures potentially related to TL.…”