Exploring perinatal biopsychosocial factors and epigenetic age in 1-year-old offspring.

Background: Little is known about the determinants of epigenetic aging in pediatric populations. Methods: Epigenetic age was estimated from 258 1-year-olds, using pediatric buccal epigenetic and Horvath clocks. We explored associations between epigenetic age and maternal indicators of mental and relational health, substance use and general physical health assessed during trimester three. Results: Higher anxiety and stress, BMI and higher parent-parent relationship quality were associated with pediatric buccal epigenetic clock differences. High blood pressure during pregnancy was associated with Horvath age acceleration. Third-trimester smoking and pre-pregnancy weight were associated with acceleration and deceleration respectively, and concordant across clocks. Conclusion: A broad range of maternal factors may shape epigenetic age in infancy; further research is needed to explore the possible effects on health and development.

Molecules on our DNA, called DNA methylation, can be used in a laboratory test to estimate how old we are ­ also known as epigenetic age. In adults, a higher risk of age-related disease has been attributed to older epigenetic age. However, we know very little about epigenetic age in children. In this study, we look at the how measures of a mother's health during pregnancy ­ such as using alcohol or tobacco, mental health (stress, anxiety and depression), or general health such as weight or high blood pressure ­ affect epigenetic age in children.

DNA methylation analysis of candidate genes associated with dementia in peripheral blood.

Aim: To investigate whether genes implicated in dementia pathogenesis are differently methylated in peripheral blood. Materials & methods: Participants included 160 cognitively healthy individuals aged 70+ years: 73 who were subsequently diagnosed with dementia and 87 controls matched on age, gender, education, smoking and baseline cognition. A total of 49 participants also provided blood samples at diagnosis. Blood DNA methylation of APOE, APP, BDNF, PIN1, SNCA and TOMM40 was examined. Results: A total of 56 of 299 probes were differentially methylated in dementia compared with controls and 39 probes prior to diagnosis. The greatest effect size was in APP (cg19423170, Δ-8.32%, adjusted p = 0.009 at diagnosis; cg19933173, Δ-4.18%, adjusted p < 0.0001 prediagnosis). Conclusion: Genes implicated in dementia pathogenesis show differential blood methylation in dementia, even prior to diagnosis.

A Systematic Review and Meta-analysis of Environmental, Lifestyle, and Health Factors Associated With DNA Methylation Age.

DNA methylation (DNAm) algorithms of biological age provide a robust estimate of an individual's chronological age and can predict their risk of age-related disease and mortality. This study reviewed the evidence that environmental, lifestyle and health factors are associated with the Horvath and Hannum epigenetic clocks. A systematic search identified 61 studies. Chronological age was correlated with DNAm age in blood (median .83, range .13-.99). In a meta-analysis body mass index (BMI) was associated with increased DNAm age (Hannum ß: 0.07, 95% CI 0.04 to 0.10; Horvath ß: 0.06, 95% CI 0.02 to 0.10), but there was no association with smoking (Hannum ß: 0.12, 95% CI -0.50 to 0.73; Horvath ß:0.18, 95% CI -0.10 to 0.46). DNAm age was positively associated with frailty (three studies, n = 3,093), and education was negatively associated with the Hannum estimate of DNAm age specifically (four studies, n = 13,955). For most other exposures, findings were too inconsistent to draw conclusions. In conclusion, BMI was positively associated with biological aging measured using DNAm, with some evidence that frailty also increased aging. More research is needed to provide conclusive evidence regarding other exposures. This field of research has the potential to provide further insights into how to promote slower biological aging and ultimately prolong healthy life.

The epigenetic clock as a predictor of disease and mortality risk: a systematic review and meta-analysis.

BACKGROUND: Ageing is one of the principal risk factors for many chronic diseases. However, there is considerable between-person variation in the rate of ageing and individual differences in their susceptibility to disease and death. Epigenetic mechanisms may play a role in human ageing, and DNA methylation age biomarkers may be good predictors of age-related diseases and mortality risk. The aims of this systematic review were to identify and synthesise the evidence for an association between peripherally measured DNA methylation age and longevity, age-related disease, and mortality risk. METHODS: A systematic search was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using relevant search terms, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and PsychINFO databases were searched to identify articles meeting the inclusion criteria. Studies were assessed for bias using Joanna Briggs Institute critical appraisal checklists. Data was extracted from studies measuring age acceleration as a predictor of age-related diseases, mortality or longevity, and the findings for similar outcomes compared. Using Review Manager 5.3 software, two meta-analyses (one per epigenetic clock) were conducted on studies measuring all-cause mortality. RESULTS: Twenty-three relevant articles were identified, including a total of 41,607 participants. Four studies focused on ageing and longevity, 11 on age-related disease (cancer, cardiovascular disease, and dementia), and 11 on mortality. There was some, although inconsistent, evidence for an association between increased DNA methylation age and risk of disease. Meta-analyses indicated that each 5-year increase in DNA methylation age was associated an 8 to 15% increased risk of mortality. CONCLUSION: Due to the small number of studies and heterogeneity in study design and outcomes, the association between DNA methylation age and age-related disease and longevity is inconclusive. Increased epigenetic age was associated with mortality risk, but positive publication bias needs to be considered. Further research is needed to determine the extent to which DNA methylation age can be used as a clinical biomarker.

Cannabis use by women during pregnancy does not influence infant DNA methylation of the dopamine receptor DRD4.

BACKGROUND: Maternal cannabis use in pregnancy is linked with long-term adverse behavioral outcomes in offspring. Epigenetic processes established in utero that affect dopaminergic (reward) signaling may mediate risks. Associations between cannabis use and offspring DNA methylation have not been investigated; however, maternal tobacco smoking in pregnancy is associated with distinct patterns of DNA methylation at birth and beyond. OBJECTIVES: To determine whether maternal cannabis use is associated with methylation of the dopamine receptor gene DRD4 promoter in infants. METHODS: Mothers in the Triple B study provided detailed information on drug use in each trimester of pregnancy. Buccal swabs were collected from neonates at 8 weeks (n = 804, 51.7% male, and 48.3% female). DRD4 promoter DNA methylation was measured using SEQUENOM MassARRAY. RESULTS: Fifty-seven of the women in the study reported drug use during pregnancy, of whom 44 used cannabis. Of 19 cytosine-phosphate-guanine dinucleotides (CpG) units tested in DRD4, gestational cannabis use was associated with offspring methylation at 1 CpG unit in multivariate models (ß + 1.48, CI: 0.02 to 2.93, and p = 0.047). At another site there was weak evidence that both cannabis and other drug use were independently associated with increased methylation, while the association with tobacco was in the reverse direction (cannabis use ß + 0.67, CI: -0.12 to 1.46, and p = 0.09; other drug use ß + 1.11, CI: 0.17 to 2.05, and p = 0.02; tobacco use ß -0.41, CI: -0.85 to 0.03, and p = 0.07). None of the associations would remain significant after correction for multiple testing. CONCLUSION: There is no strong evidence that maternal cannabis use in pregnancy is associated with offspring DRD4 methylation.