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Association between epigenetic age acceleration and depressive symptoms in a prospective cohort study of urban-dwelling adults.

ABSTRACT: OBJECTIVE:This study tests associations of DNA methylation-based (DNAm) measures of epigenetic age acceleration (EAA) with cross-sectional and longitudinal depressive symptoms in an urban sample of middle-aged adults. METHODS:White and African-American adult participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span study for whom DNA samples were analyzed (baseline age: 30-65 years) we included. We estimated three DNAm based EAA measures: (1) universal epigenetic age acceleration (AgeAccel); (2) intrinsic epigenetic age acceleration (IEAA); and (3) extrinsic epigenetic age acceleration (EEAA). Depressive symptoms were assessed using the 20-item Center for Epidemiological Studies-Depression scale total and sub-domain scores at baseline (2004-2009) and follow-up visits (2009-2013). Linear mixed-effects regression models were conducted, adjusting potentially confounding covariates, selection bias and multiple testing (N?=?329 participants, ?52% men, k?=?1.9 observations/participant, mean follow-up time?4.7 years). RESULTS:None of the epigenetic age acceleration measures were associated with total depressive symptom scores at baseline or over time. IEAA - a measure of cellular epigenetic age acceleration irrespective of white blood cell composition - was cross-sectionally associated with decrement in "positive affect" in the total population (?011± SE = -0.090?±?0.030, P?=?0.003, Cohen's D: -0.16) and among Whites (?011?±?SE?=?-0.135?± 0.048, P?=?0.005, Cohen's D: -0.23), after correction for multiple testing. Baseline "positive affect" was similarly associated with AgeAccel. LIMITATIONS:Limitations included small sample size, weak-moderate effects and measurement error. CONCLUSIONS:IEAA and AgeAccel, two measures of EAA using Horvath algorithm, were linked to a reduced "positive affect", overall and among Whites. Future studies are needed to replicate our findings and test bi-directional relationships.

SUBMITTER: Beydoun MA

PROVIDER: S-EPMC6757325 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Association between epigenetic age acceleration and depressive symptoms in a prospective cohort study of urban-dwelling adults.

Beydoun May A MA Hossain Sharmin S Chitrala Kumaraswamy Naidu KN Tajuddin Salman M SM Beydoun Hind A HA Evans Michele K MK Zonderman Alan B AB

Journal of affective disorders 20190630

<h4>Objective</h4>This study tests associations of DNA methylation-based (DNAm) measures of epigenetic age acceleration (EAA) with cross-sectional and longitudinal depressive symptoms in an urban sample of middle-aged adults.<h4>Methods</h4>White and African-American adult participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span study for whom DNA samples were analyzed (baseline age: 30-65 years) we included. We estimated three DNAm based EAA measures: (1) universal e ...[more]

PMID: 31299406

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Project description:BackgroundGestational age at delivery is associated with health and social outcomes. Recently, cord blood DNA methylation data has been used to predict gestational age. The discrepancy between gestational age predicted from DNA methylation and determined by ultrasound or last menstrual period is known as gestational age acceleration. This study investigated associations of sex, socioeconomic status, parental behaviours and characteristics and birth outcomes with gestational age acceleration.ResultsUsing data from the Avon Longitudinal Study of Parents and Children (n = 863), we found that pre-pregnancy maternal overweight and obesity were associated with greater gestational age acceleration (mean difference = 1.6 days, 95% CI 0.7 to 2.6, and 2.9 days, 95% CI 1.3 to 4.4, respectively, compared with a body mass index < 25 kg/m2, p < .001). There was evidence of an association between male sex and greater gestational age acceleration. Greater gestational age acceleration was associated with higher birthweight, birth length and head circumference of the child (mean differences per week higher gestational age acceleration: birthweight 0.1 kg, 95% CI 0.1 to 0.2, p < .001; birth length 0.4 cm, 95% CI 0.2 to 0.7, p < .001; head circumference 0.2 cm, 95% CI 0.1 to - 0.4, p < .001). There was evidence of an association between gestational age acceleration and mode of delivery (assisted versus unassisted delivery, odds ratio = 0.9 per week higher gestational age acceleration, 95% CI 0.7, 1.3 (p = .05); caesarean section versus unassisted delivery, odds ratio = 0.6, 95% CI 0.4 to 0.9 per week higher gestational age acceleration (p = .05)). There was no evidence of association for other parental and perinatal characteristics.ConclusionsThe associations of higher maternal body mass index and larger birth size with greater gestational age acceleration may imply that maternal overweight and obesity is associated with more rapid development of the fetus in utero. The implications of gestational age acceleration for postnatal health warrant further investigation.

Project description:Study questionIs the use of ART, a proxy for infertility, associated with epigenetic age acceleration?Summary answerThe epigenetic age acceleration measured by Dunedin Pace of Aging methylation (DunedinPoAm) differed significantly between non-ART and ART mothers.What is known alreadyAmong mothers who used ART, epigenetic age acceleration may be associated with low oocyte yield and poor ovarian response. However, the difference in epigenetic age acceleration between non-ART and ART mothers (or even fathers) has not been examined.Study design, size, durationThe Norwegian Mother, Father and Child Cohort Study (MoBa) recruited pregnant women and their partners across Norway at around 18 gestational weeks between 1999 and 2008. Approximately 95 000 mothers, 75 000 fathers and 114 000 children were included. Peripheral blood samples were taken from mothers and fathers at ultrasound appointments or from mothers at childbirth, and umbilical cord blood samples were collected from the newborns at birth.Participants/materials, setting, methodsAmong the MoBa participants, we selected 1000 couples who conceived by coitus and 894 couples who conceived by IVF (n = 525) or ICSI (n = 369). We measured their DNA methylation (DNAm) levels using the Illumina MethylationEPIC array and calculated epigenetic age acceleration. A linear mixed model was used to examine the differences in five different epigenetic age accelerations between non-ART and ART parents.Main results and the role of chanceWe found a significant difference in the epigenetic age acceleration calculated by DunedinPoAm between IVF and non-ART mothers (0.021 years, P-value = 2.89E-06) after adjustment for potential confounders. Further, we detected elevated DunedinPoAm in mothers with tubal factor infertility (0.030 years, P-value = 1.34E-05), ovulation factor (0.023 years, P-value = 0.0018) and unexplained infertility (0.023 years, P-value = 1.39E-04) compared with non-ART mothers. No differences in epigenetic age accelerations between non-ART and ICSI fathers were found. DunedinPoAm also showed stronger associations with smoking, education and parity than the other four epigenetic age accelerations.Limitations, reasons for cautionWe were not able to determine the directionality of the causal pathway between the epigenetic age accelerations and infertility. Since parents' peripheral blood samples were collected after conception, we cannot rule out the possibility that the epigenetic profile of ART mothers was influenced by the ART treatment. Hence, the results should be interpreted with caution, and our results might not be generalizable to non-pregnant women.Wider implications of the findingsA plausible biological mechanism behind the reported association is that IVF mothers could be closer to menopause than non-ART mothers. The pace of decline of the ovarian reserve that eventually leads to menopause varies between females yet, in general, accelerates after the age of 30, and some studies show an increased risk of infertility in females with low ovarian reserve.Study funding/competing interest(s)This study was partly funded by the Research Council of Norway (Women's fertility, project no. 320656) and through its Centres of Excellence Funding Scheme (project no. 262700). M.C.M. has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement number 947684). The authors declare no conflict of interest.Trial registration numberN/A.

Project description:BACKGROUND:Instrumental Activities of Daily Living (IADL) is an indicator of whether a community-dwelling elderly can live independently. IADL decline was reported to be associated with aging and depression. The present study aimed to investigate whether the association between IADL decline and depressive symptoms differs with aging, using two age groups of community-dwelling Japanese elderly in their 70s and 80s. METHODS:We conducted longitudinal analysis among participants in their 70s and 80s at the baseline from Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians (SONIC) study. IADL was assessed by The Tokyo Metropolitan Institute of Gerontology (TMIG) index of competence. As a main predictor, depressive symptoms were measured by the five-item version of the Geriatrics Depression Scale (GDS-5). As possible confounders, we considered cognitive function, body mass index, solitary living, education, economic status, medical history of stroke and heart disease, hypertension, dyslipidemia, diabetes, and sex. We obtained odds ratios (ORs) of IADL decline for having depressive symptoms in each age group (70s/80s) and tested interactions between depressive symptoms and age groups in relation to IADL decline in 3 years by logistic regression. Additionally, to confirm age group differences, we conducted multiple group analysis. RESULTS:There were 559 participants in their 70s and 519 in their 80s. Compared to participants without depressive symptoms, those with depressive symptoms had higher OR of IADL decline in 70s (OR [95% CI] = 2.33 [1.13, 4.78]), but not in 80s (OR [95% CI] = 0.85 [0.46, 1.53]). There were significant interactions between depressive symptoms and age groups in relation to IADL decline (p-value = 0.03). Multiple group analyses showed differences between the age groups by Akaike information criterion (AIC), and ORs (95%CI) decline for depressive symptoms was 2.33 (1.14, 4.77) in 70s and 0.85 (0.47, 1.54) in 80s. CONCLUSION:The association of depressive symptoms and IADL decline during the 3 years was significantly different between the 70s and 80s age groups, and significant association was found only in people in their 70s. Detecting depressive symptoms may be a key for preventing IADL decline in people in their 70s and not for those in their 80s.

Dataset Information

Association between epigenetic age acceleration and depressive symptoms in a prospective cohort study of urban-dwelling adults.

Publications

Association between epigenetic age acceleration and depressive symptoms in a prospective cohort study of urban-dwelling adults.

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