Dataset Information

Sleep and Methylation of Estrogen Receptor Genes, ESR1 and GPER, in Healthy Middle-Aged and Older Women: Findings from the Women 40+ Healthy Aging Study.

ABSTRACT: Purpose:Sleep problems in middle-aged and older women are very common and have been associated with menopause-related changes in estrogen levels. However, not all women experience sleep problems as they enter perimenopause, and epigenetic mechanisms might contribute to the differences in sleep quality within this population. In this study, we hypothesized that increased methylation of two estrogen receptor (ER) genes (ESR1 and GPER) would be associated with increased sleep problems in healthy pre-, peri-, and postmenopausal women, either directly or indirectly through the experience of vasomotor symptoms (VMS). Materials and Methods:In 130 healthy women aged 40-73 years, we assessed DNA methylation from dried blood spots (DBS). Women rated their sleep quality using the Pittsburgh Sleep Quality Index (PSQI), and VMS using the Menopause Rating Scale (MRS). Results:Higher percentage methylation of ESR1 was associated with increased sleep problems, mediated by VMS, even after controlling for age, menopausal status, body mass index, estradiol levels, depressive symptoms, and caffeine consumption. There was no significant association between GPER methylation and either sleep problems or VMS. Conclusion:The study findings support an association between increased ESR1 methylation and sleep problems through increased VMS among healthy women aged 40-73 years.

SUBMITTER: Gardini ES

PROVIDER: S-EPMC7394583 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Sleep and Methylation of Estrogen Receptor Genes, <i>ESR1</i> and <i>GPER</i>, in Healthy Middle-Aged and Older Women: Findings from the Women 40+ Healthy Aging Study.

Gardini Elena S ES Fiacco Serena S Mernone Laura L Ehlert Ulrike U

Nature and science of sleep 20200727

<h4>Purpose</h4>Sleep problems in middle-aged and older women are very common and have been associated with menopause-related changes in estrogen levels. However, not all women experience sleep problems as they enter perimenopause, and epigenetic mechanisms might contribute to the differences in sleep quality within this population. In this study, we hypothesized that increased methylation of two estrogen receptor (ER) genes (<i>ESR1</i> and <i>GPER</i>) would be associated with increased sleep ...[more]

PMID: 32801978

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Project description:Background: Adversity in early development seems to increase the risk of stress-related somatic disorders later in life. Physiologically, functioning of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes is often discussed as long-term mediators of risk. In particular, DNA methylation in the glucocorticoid receptor gene promoter (NR3C1) has been associated with type and strength of early life adversity and subsequent effects on HPA axis signaling in humans. Animal studies, moreover, suggest changes in DNA methylation in the estrogen receptor gene (ER?) upon early life adversity. We investigated the association of type and severity of childhood adversity with methylation in NR3C1 and ER? and additionally considered associations between methylation and steroid hormone secretion. Methods: The percentage of methylation within the NR3C1 promoter and the ER? shore was investigated using dried blood spot samples of 103 healthy women aged 40-73 years. Childhood adversity was examined with the Childhood Trauma Questionnaire. Linear regression analyses were performed with methylation as dependent variable and the experience of emotional abuse and neglect, physical abuse and neglect, and sexual abuse (compared to non-experience) as independent variables. All analyses were controlled for age, BMI, annual household income, and smoking status and were adjusted for multiple testing. Results: Overall, over 70% of the sample reported having experienced any kind of abuse or neglect of at least low intensity. There were no significant associations between childhood adversity and methylation in the NR3C1 promoter (all p > .10). Participants reporting emotional abuse showed significantly higher methylation in the ER? shore than those who did not (p = .001). Additionally, higher levels of adversity were associated with higher levels of ER? shore methylation (p = .001). Conclusion: In healthy women, early life adversity does not seem to result in NR3C1 promoter hypermethylation in midlife and older age. This is the first study in humans to suggest that childhood adversity might, however, epigenetically modify the ER? shore. Further studies are needed to gain a better understanding of why some individuals remain healthy and others develop psychopathologies in the face of childhood adversity.

Project description:BackgroundWhile efforts have been made to validate intrinsic capacity (IC) as a multidimensional indicator of healthy aging in high-income countries, we still need evidence from lower-income countries. We examined associations of IC with wide ranges of activities of daily living in a nationally representative sample of Brazilians aged≥50 years.MethodsThis cross-sectional analysis included 7175 participants from the Brazilian Longitudinal Study of Aging. IC domains (cognitive, psychological, sensory, locomotor, and vitality) were determined using self-reported and physical performance measures. IC was operationalized through factorial analysis. We investigated associations of IC and its domains with functional ability in basic, instrumental, and advanced activities of daily living (ADL, IADL, and AADL) using logistic regressions adjusted for sociodemographic, clinical, and modifiable risk factors.FindingsThe IC bi-factorial model revealed satisfactory goodness-of-fit. Preserved ability in ADL and IADL, respectively, ranged from 69% and 29% to 89% and 74% across IC quartiles. In adjusted analyses, every standard deviation increment in IC composite score was associated with almost twice the odds of preserved ADL (OR=1·72; 95%CI=1·54-1·93), preserved IADL (OR=1·95; 95%CI=1·77-2·16), and high performance in AADL (OR=1·79; 95%CI=1·59-2·00). Similar results were reported using the IC domains as predictors. Although age, race/ethnicity, and education did not modify associations of IC with functional ability, we found sex differences with stronger relationships of IC with preserved ADL or IADL in females.InterpretationOur results support IC validity and reliability to measure healthy aging in diverse socioeconomic and cultural settings. Incorporating IC in routine practices can promote holistic and person-centered care approaches in aging societies.FundingThe Brazilian Ministry of Health and Ministry of Science, Technology, Innovation, and Communication.

Dataset Information

Sleep and Methylation of Estrogen Receptor Genes, ESR1 and GPER, in Healthy Middle-Aged and Older Women: Findings from the Women 40+ Healthy Aging Study.

Publications

Sleep and Methylation of Estrogen Receptor Genes, <i>ESR1</i> and <i>GPER</i>, in Healthy Middle-Aged and Older Women: Findings from the Women 40+ Healthy Aging Study.

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