DNA methylation GrimAge version 2

We previously described a DNA methylation (DNAm) based biomarker of human mortality risk DNAm GrimAge. Here we describe version 2 of GrimAge (trained on individuals aged between 40 and 92) which leverages two new DNAm based estimators of (log transformed) plasma proteins: high sensitivity C-reactive protein (logCRP) and hemoglobin A1C (logA1C). We evaluate GrimAge2 in 13,399 blood samples across nine study cohorts. After adjustment for age and sex, GrimAge2 outperforms GrimAge in predicting mortality across multiple racial/ethnic groups (meta P=3.6x10-167 versus P=2.6x10-144) and in terms of associations with age related conditions such as coronary heart disease, lung function measurement FEV1 (correlation= -0.31, P=1.1x10-136), computed tomography based measurements of fatty liver disease. We present evidence that GrimAge version 2 also applies to younger individuals and to saliva samples where it tracks markers of metabolic syndrome. DNAm logCRP is positively correlated with morbidity count (P=1.3x10-54). DNAm logA1C is highly associated with type 2 diabetes (P=5.8x10-155). DNAm PAI-1 outperforms the other age-adjusted DNAm biomarkers including GrimAge2 in correlating with triglyceride (cor=0.34, P=9.6x10-267) and visceral fat (cor=0.41, P=4.7x10-41). Overall, we demonstrate that GrimAge version 2 is an attractive epigenetic biomarker of human mortality and morbidity risk

Early life adversity, pubertal timing, and epigenetic age acceleration in adulthood

BackgroundGiven associations linking early life adversity, pubertal timing, and biological aging, we examined the direct and indirect effects of early life trauma on adult biological aging (via age of menarche).MethodsParticipants were premenopausal women (N = 183). Path models evaluated whether early life trauma predicted early pubertal timing and thereby, adult epigenetic age acceleration (indexed via four epigenetic clocks: Horvath DNAm Age, Hannum DNAm Age, DNAm PhenoAge, and DNAm GrimAge). Secondary analyses explored the effects of type of trauma (abuse and neglect) and adult chronic stress status (caregiver of child with autism and non-caregiver).ResultsEarly life trauma and earlier age at menarche independently predicted accelerated aging based on one of the four epigenetic clocks, DNAm GrimAge, though early life trauma was not associated with age of menarche. Childhood abuse, but not neglect, predicted faster epigenetic aging; results did not differ by chronic stress status.ConclusionsEarly trauma and early menarche appear to exert independent effects on DNAm GrimAge, which has been shown to be the strongest epigenetic predictor of mortality risk. This study identifies a potential correlate or determinant of accelerated epigenetic aging-menarcheal age. Future research should address the limitations of this study by using racially diverse samples

Childhood stress and midlife depression in women: the influence of diet quality

ObjectiveHow does diet quality (DQ) moderate associations between serious childhood stress exposures and adult depression?MethodsWe analyzed a cohort of Californian women at midlife (N=382; age 36-42). Serious childhood stress was defined as high perceived stress during childhood or adverse childhood experiences (ACEs) of physical abuse, sexual abuse, and/or household substance abuse. Women were dichotomized by current depression risk (high/low). The Healthy Eating Index (HEI)-2015 and Alternate Healthy Eating Index (AHEI)-2010 measured current DQ from 3-day food records. Interactions between childhood stress exposures and DQ indices were tested one-by-one in multivariable Poisson regression models.ResultsDepression risks associated with endorsing all 3 ACEs differed by HEI and AHEI scores, as did risks associated with endorsing high perceived stress, physical abuse, and sexual abuse by AHEI. Where DQ moderated stress-depression associations, predicted prevalences of high depression risk did not vary with DQ among women endorsing the particular childhood stressors. However, among non-endorsing women, predicted high depression risk prevalences were significantly lower with higher DQ compared to in their stress-exposed counterparts - e.g. at the 90th AHEI percentile, depression prevalences were ∼20% among 'non-childhood-stressed' women versus 48.8% (high perceived stress, sexual abuse), 52.0% (physical abuse), and 73.0% (3 ACEs) in 'childhood-stressed' women.ConclusionsHigher current DQ, particularly as aligned with chronic disease prevention guidelines, predicts lower depression risk in women with low childhood adversity. DQ did not buffer depression risk in women with high childhood stress. Further research is warranted to examine persistent pathways of depression risk and diet's role within

Early pubertal timing predicts onset and recurrence of depressive episodes in boys and girls

BackgroundRecurrent depressive episodes during adolescence result in significant impairment and increased risk for subsequent adverse outcomes throughout the life span. Evidence suggests that early pubertal timing predicts the onset of depressive episodes (particularly for girls); however, it is not known if pubertal timing prospectively predicts recurrent depressive episodes in youth.MethodsAt baseline, 603 youth (56% female, at baseline: Mage  = 12.09, SD = 2.35) reported on their pubertal development. Youth and their parents completed a semistructured diagnostic interview to assess depressive episodes at baseline and then evaluated for onset repeatedly every 6 months for a period of 36 months.ResultsControlling for past history of depression, Cox proportional hazards models examined whether earlier pubertal timing predicted (a) days to first depressive episode from baseline and (b) days to a second (recurrent) depressive episode from the end of the first episode. Early pubertal timing predicted the onset of the first depressive episode after baseline (b = .19, Wald = 5.36, p = .02, HR = 1.21), as well as a recurrent episode during course of study follow-up episode (b = .32, Wald = 6.16, p = .01, HR = 1.38).ConclusionsFindings reinforce the importance of considering the impact of early pubertal timing on depression risk. Investigation on how pubertal timing interacts with other risk factors to predict depression recurrence is needed

Association of subjective social status with epigenetic aging among Black and White women

ObjectiveSubjective social status (SSS), an individual's assessment of their own social status in relation to others, is associated with health and mortality independently of objective SES; however, no studies have tested whether SSS influences epigenetic aging. The current study examines if SSS is associated with epigenetic age acceleration in both Black and White women, independently of objective SES measured during both childhood and adulthood.MethodFor 9- and 10-year-old Black and White girls, parental education and annual household income was obtained. At ages 39-42, 361 participants (175 Black, 186 White) reported their current education, household income, and SSS, and provided saliva to assess age acceleration using the GrimAge epigenetic clock. Linear regression estimated the association of SSS with epigenetic age acceleration, controlling for objective SES (current education, current income, parents' education, income during childhood), smoking, and counts of cell types.ResultsWhen all objective SES variables were included in the model, SSS remained significantly associated with epigenetic age acceleration, b = - 0.31, p = .003, ß = - 0.15. Black women had significantly greater age acceleration than White women, (t(359) = 5.20, p > .001, d = 0.55) but race did not moderate the association between SSS and epigenetic age acceleration.ConclusionsWomen who rated themselves lower in SSS had greater epigenetic age acceleration, regardless of income and education. There was no difference by race for this association