Search

Background: Exposure to famine in the prenatal period is associated with an increased risk of metabolic disease, including obesity and type 2 diabetes. We employed nuclear magnetic resonance (NMR) metabolomic profiling to identify the metabolic changes that are associated with survival of prenatal famine exposure during the Dutch Famine at the end of World War II and subsequently assess their link to disease. Methods: NMR metabolomics data were generated from serum in 480 individuals prenatally exposed to famine (mean 58.8 years, 0.5 SD) and 464 controls (mean 57.9 years, 5.4 SD). We tested associations of prenatal famine exposure with levels of 168 individual metabolic biomarkers and compared the metabolic biomarker signature of famine exposure with those of 154 common diseases. Results: Prenatal famine exposure was associated with higher concentrations of branched-chain amino acids ((iso)-leucine), aromatic amino acid (tyrosine), and glucose in later life (0.2–0.3 SD, p < 3 × 10−3). The metabolic biomarker signature of prenatal famine exposure was positively correlated to that of incident type 2 diabetes from the UK Biobank (r = 0.77, p = 3 × 10−27), also when re-estimating the signature of prenatal famine exposure among individuals without diabetes (r = 0.67, p = 1 × 10−18). Remarkably, this association extended to 115 common diseases for which signatures were available (0.3 ≤ r ≤ 0.9, p < 3.2 × 10−4). Correlations among metabolic signatures of famine exposure and disease outcomes were attenuated when the famine signature was adjusted for body mass index. Conclusions: Prenatal famine exposure is associated with a metabolic biomarker signature that strongly resembles signatures of a diverse set of diseases, an observation that can in part be attributed to a shared involvement of obesity. [ABSTRACT FROM AUTHOR]

Theory predicts that biological processes of aging may contribute to poor mental health in late life. To test this hypothesis, we evaluated prospective associations between biological age and incident depression and anxiety in 424,299 UK Biobank participants. We measured biological age from clinical traits using the KDM-BA and PhenoAge algorithms. At baseline, participants who were biologically older more often experienced depression/anxiety. During a median of 8.7 years of follow-up, participants with older biological age were at increased risk of incident depression/anxiety (5.9% increase per standard deviation [SD] of KDM-BA acceleration, 95% confidence intervals [CI]: 3.3%–8.5%; 11.3% increase per SD of PhenoAge acceleration, 95% CI: 9.%–13.0%). Biological-aging-associated risk of depression/anxiety was independent of and additive to genetic risk measured by genome-wide-association-study-based polygenic scores. Advanced biological aging may represent a potential risk factor for incident depression/anxiety in midlife and older adults and a potential target for risk assessment and intervention. Theory indicates that biological aging may contribute to poor mental health in late life. Here, authors show advanced biological aging may represent a potential risk factor for incident depression/anxiety in midlife and older adults and a potential target for risk assessment and intervention. [ABSTRACT FROM AUTHOR]

This study tested implications of new genetic discoveries for understanding the association between parental investment and children's educational attainment. A novel design matched genetic data from 860 British mothers and their children with home-visit measures of parenting: the E-Risk Study. Three findings emerged. First, both mothers' and children's education-associated genetics, summarized in a genome-wide polygenic score, were associated with parenting-a gene-environment correlation. Second, accounting for genetic influences slightly reduced associations between parenting and children's attainment-indicating some genetic confounding. Third, mothers' genetics were associated with children's attainment over and above children's own genetics, via cognitively stimulating parenting-an environmentally mediated effect. Findings imply that, when interpreting parents' effects on children, environmentalists must consider genetic transmission, but geneticists must also consider environmental transmission. [ABSTRACT FROM AUTHOR]

The authors examined the role of food insecurity in the etiology of children's cognitive and mental health problems. Data from a prospective longitudinal study of 1,116 United Kingdom families with twins (sample constructed in 1999–2000) were used to test associations among household food insecurity; income; maternal personality; household sensitivity to children's needs; and children's cognitive, behavioral, and emotional development. Food-insecure children had lower IQs and higher levels of behavioral and emotional problems relative to their peers. After differences in household income, the personalities of children's mothers, and the sensitivity of household organization to children's needs were accounted for, food-insecure children had moderately higher levels of emotional problems relative to food-secure children (β = 0.22, P = 0.02). Differences in children's cognitive development were accounted for by household income, and differences in their behavioral development were accounted for by their mothers’ personalities and their households’ sensitivity to children's needs. Results suggest that food insecurity was associated with school-aged children's emotional problems but not with their cognitive or behavioral problems after accounting for differences in the home environments in which children were reared. Mothers’ personality and household sensitivity to children's needs may present challenges to improving outcomes of children with food insecurity. [ABSTRACT FROM PUBLISHER]

Children who grow up in neighborhoods with more green vegetation show enhanced cognitive development in specific domains over short timespans. However, it is unknown if neighborhood greenery per se is uniquely predictive of children's overall cognitive development measured across many years. The E-Risk Longitudinal Study, a nationally representative 1994-5 birth-cohort of children in Britain (n = 1658 urban and suburban-dwelling participants), was used to test whether residential neighborhood greenery uniquely predicts children's cognitive development across childhood and adolescence. Greenery exposure was assessed from ages 5 to 18 using the satellite imagery-based normalized difference vegetation index (NDVI) in 1-mile buffers around the home. Fluid and crystalized intellectual performance was assessed in the home at ages 5, 12, and 18 using the Wechsler Intelligence Scale, and executive function, working memory, and attention ability were assessed in the home at age 18 using the Cambridge Neuropsychological Test Automated Battery. Children living in residences surrounded by more neighborhood greenery scored significantly higher, on average, on IQ measures at all ages. However, the association between greenery and cognitive measures did not hold after accounting for family or neighborhood socioeconomic status. After adjustment for study covariates, child greenery exposure was not a significant predictor of longitudinal increases in IQ across childhood and adolescence or of executive function, working memory, or attention ability at age 18. Children raised in greener neighborhoods exhibit better overall cognitive ability, but the association is likely accounted for by family and neighborhood socioeconomic factors. • We tested whether neighborhood greenery predicts child cognitive development. • Satellite-imagery measures of greenery were related to cognitive ability assessed at ages 5, 12, and 18. • Children raised in greener neighborhoods showed greater ability at all ages. • Children raised in greener neighborhoods also showed greater growth in crystalized cognitive ability from age 5 to 12. • However, the positive associations were best accounted for by family/neighborhood socioeconomic factors. [ABSTRACT FROM AUTHOR]

Personality traits are linked with healthy aging, but it is not clear how these associations come to manifest across the life-course and across generations. To study this question, we tested a series of hypotheses about (a) personality-trait prediction of markers of healthy aging across the life-course, (b) developmental origins, stability and change of links between personality and healthy aging across time, and (c) intergenerational transmission of links between personality and healthy aging. For our analyses we used a measure that aggregates the contributions of Big 5 personality traits to healthy aging: a "vital personality" score. Data came from two population-based longitudinal cohort studies, one based in New Zealand and the other in the UK, comprising over 6000 study members across two generations, and spanning an age range from birth to late life. Our analyses revealed three main findings: first, individuals with higher vital personality scores engaged in fewer health-risk behaviors, aged slower, and lived longer. Second, individuals' vital personality scores were preceded by differences in early-life temperament and were relatively stable across adulthood, but also increased from young adulthood to midlife. Third, individuals with higher vital personality scores had children with similarly vital partners, promoted healthier behaviors in their children, and had children who grew up to have more vital personality scores themselves, for genetic and environmental reasons. Our study shows how the health benefits associated with personality accrue throughout the life-course and across generations. • A multi-trait index of 'vital personality' was derived. • Individuals with higher vital personality scores aged more slowly. • Individuals with higher vital personality scores had healthier lifestyles. • Parents with higher vital personality scores promoted healthier habits in their children. • Findings replicated in two cohorts. [ABSTRACT FROM AUTHOR]

Importance: Adverse childhood experiences (ACEs), potentially traumatic experiences occurring before the age of 18 years, are associated with epigenetic aging later in life and may be transmitted across generations., Objective: To test evidence of the transmission of biological embedding of life experience across generations by analyzing maternal ACEs and epigenetic clocks measured in mothers during pregnancy and in their children at birth., Design, Setting, and Participants: For this cross-sectional study, data from the Accessible Resource for Integrated Epigenomic Studies (ARIES) substudy of the Avon Longitudinal Study of Parents and Children (ALSPAC) were analyzed. The ALSPAC study recruited 14 541 women who gave birth in the Avon Health District in the UK between April 1, 1991, and December 31, 1992. The ARIES substudy comprised 1018 mother-offspring dyads based on the availability of DNA samples profiled in 2014. Epigenetic age was estimated using DNA methylation-based epigenetic clocks (including Horvath, Hannum, GrimAge, PhenoAge, and DunedinPACE) in mothers during pregnancy and the Knight and Bohlin cord blood epigenetic clocks in newborns. Analyses were performed between October 1, 2022, and November 30, 2023., Exposures: A composite measure of maternal ACEs was the primary exposure in both maternal and offspring models; as a secondary analysis, individual ACEs were measured separately. The Edinburgh Postnatal Depression Scale (EPDS) was used to investigate depression during pregnancy as an exposure., Main Outcomes and Measures: Changes in epigenetic age acceleration (EAA) were investigated as the primary outcome in maternal models during pregnancy. Changes in epigenetic gestational age acceleration (GAA) were the primary outcome in offspring analyses. Linear regression analyses were used to determine the association between maternal ACEs and both outcomes., Results: This study included 883 mother-child dyads. The mean (SD) maternal age at delivery was 29.8 (4.3) years. Pregnant women with higher ACE scores exhibited higher GrimAge EAA (β, 0.22 [95% CI, 0.12 to 0.33] years; P < .001). Maternal ACEs were not associated with GAA in newborns using P < .05 as a cutoff to determine statistical significance. Depression was associated with higher GrimAge EAA (β, 0.06 [95% CI, 0.02 to 0.10] years; P = .01) in mothers during pregnancy, but not in newborns, and did not mediate the association between ACEs and EAA., Conclusions and Relevance: The findings of this study suggest that maternal ACEs may be associated with epigenetic aging later in life, including during pregnancy, supporting a role for maternal ACEs in offspring development and health later in life.

Associations of biological aging with the development and mortality of cardiometabolic multimorbidity (CMM) remain unclear. Here we conducted a multistate analysis in 341,159 adults of the UK Biobank. CMM was defined as the coexistence of two or three cardiometabolic diseases (CMDs), including type 2 diabetes, ischemic heart disease and stroke. Biological aging was measured using the Klemera-Doubal Method Biological Age and PhenoAge algorithms. Over a median follow-up of 8.84 years, biologically older participants demonstrated robust higher risks from first CMD to CMM and then to death. In particular, adjusted hazard ratios for first CMD to CMM and for CMM to death were 1.15 (95% confidence interval (CI): 1.12, 1.19) and 1.26 (95% CI: 1.17, 1.35) per 1 s.d. increase in PhenoAge acceleration, respectively. Compared with frailty, Framingham Risk Score and Systematic Coronary Risk Evaluation 2 (SCORE2), biological aging measures yielded consistent substantial associations with CMM development. Accelerated biological aging may help identify individuals with CMM risks, potentially enabling early intervention and subclinical prevention., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

People who score higher on intelligence tests tend to have larger brains. Twin studies suggest the same genetic factors influence both brain size and intelligence. This has led to the hypothesis that genetics influence intelligence partly by contributing to the development of larger brains. We tested this hypothesis using four large imaging genetics studies (combined N = 7965) with polygenic scores derived from a genome-wide association study (GWAS) of educational attainment, a correlate of intelligence. We conducted meta-analysis to test associations among participants' genetics, total brain volume (i.e., brain size), and cognitive test performance. Consistent with previous findings, participants with higher polygenic scores achieved higher scores on cognitive tests, as did participants with larger brains. Participants with higher polygenic scores also had larger brains. We found some evidence that brain size partly mediated associations between participants' education polygenic scores and their cognitive test performance. Effect sizes were larger in the population-based samples than in the convenience-based samples. Recruitment and retention of population-representative samples should be a priority for neuroscience research. Findings suggest promise for studies integrating GWAS discoveries with brain imaging to understand neurobiology linking genetics with cognitive performance., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)