In differentiated cells, aging is associated with hypermethylation of DNA regions enriched in repressive histone posttranslational modifications. However, the chromatin marks associated with changes in DNA methylation in adult stem cells during lifetime are still largely unknown. Here, DNA methylation profiling of mesenchymal stem cells (MSCs) obtained from individuals aged 2 to 92 yr identified 18,735 hypermethylated and 45,407 hypomethylated CpG sites associated with aging. As in differentiated cells, hypermethylated sequences were enriched in chromatin repressive marks. Most importantly, hypomethylated CpG sites were strongly enriched in the active chromatin mark H3K4me1 in stem and differentiated cells, suggesting this is a cell type-independent chromatin signature of DNA hypomethylation during aging. Analysis of scedasticity showed that interindividual variability of DNA methylation increased during aging in MSCs and differentiated cells, providing a new avenue for the identification of DNA methylation changes over time. DNA methylation profiling of genetically identical individuals showed that both the tendency of DNA methylation changes and scedasticity depended on nongenetic as well as genetic factors. Our results indicate that the dynamics of DNA methylation during aging depend on a complex mixture of factors that include the DNA sequence, cell type, and chromatin context involved and that, depending on the locus, the changes can be modulated by genetic and/or external factors.
We investigated the heritability of educational attainment and how it differed between birth cohorts and cultural-geographic regions. A classical twin design was applied to pooled data from 28 cohorts representing 16 countries and including 193,518 twins with information on educational attainment at 25 years of age or older. Genetic factors explained the major part of individual differences in educational attainment (heritability: a 2 = 0.43; 0.41-0.44), but also environmental variation shared by co-twins was substantial (c 2 = 0.31; 0.30-0.33). The proportions of educational variation explained by genetic and shared environmental factors did not differ between Europe, North America and Australia, and East Asia. When restricted to twins 30 years or older to confirm finalized education, the heritability was higher in the older cohorts born in 1900-1949 (a 2 = 0.44; 0.41-0.46) than in the later cohorts born in 1950-1989 (a 2 = 0.38; 0.36-0.40), with a corresponding lower influence of common environmental factors (c 2 = 0.31; 0.29-0.33 and c 2 = 0.34; 0.32-0.36, respectively). In conclusion, both genetic and environmental factors shared by co-twins have an important influence on individual differences in educational attainment. The effect of genetic factors on educational attainment has decreased from the cohorts born before to those born after the 1950s.
Depression is a worldwide public health concern. The World Health Organization (WHO) has recently recommended the implementation of programs for strengthening subjective well-being (SWB) to reduce mental disorders, including depression. Also, in 2013, European member-states agreed on a single measure of SWB, i.e., life satisfaction, for monitoring the progress of SWB in the WHO health policy framework, “Health 2020.” Life satisfaction is strongly associated with depression; therefore, its use as health indicator could be suitable to identify individuals at risk for depression. Critical to this use of life satisfaction to target also depression is knowledge on the nature of the association between the two throughout the lifespan and by gender. This study aims at contributing to the knowledge about this association in a sample of 51 individuals screened for major depressive disorder (MDD) and dysthymic disorder (Dys). All individuals were administered the Primary Care Screener for Affective Disorders and the Satisfaction With Life Scale (SWLS). Among individuals negative for MDD or Dys, women displayed similar satisfaction compared with men, whereas among individuals positive for MDD or Dys, women showed greater satisfaction compared with men, whose score denoted life dissatisfaction. Consistently, the regression model for SWLS revealed a significant main effect of positivity for MDD or Dys on life satisfaction as well as a significant interaction between positivity for MDD or Dys and gender. The results of this study do not support the notion that satisfaction with life and depressive symptoms could belong to highly related dimensions, at least among female individuals.
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