Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Abstract Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci ass…
Additional file 4 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 4. Assessment of genomic inflation and heterogeneity.
Hormone Replacement Therapy Associated White Blood Cell DNA Methylation and Gene Expression are Associated With Within-Pair Differences of Body Adiposity and Bone Mass.
The loss of estrogen during menopause causes changes in the female body, with wide-ranging effects on health. Estrogen-containing hormone replacement therapy (HRT) leads to a relief of typical menopausal symptoms, benefits bone and muscle health, and is associated with tissue-specific gene expression profiles. As gene expression is controlled by epigenetic factors (including DNA methylation), many of which are environmentally sensitive, it is plausible that at least part of the HRT-associated gene expression is due to changes in DNA methylation profile. We investigated genome-wide DNA methylation and gene expression patterns of white blood cells (WBCs) and their associations with body compo…
The Association Between Epigenetic Clocks and Physical Functioning in Older Women: A 3-Year Follow-up
Abstract Background Epigenetic clocks are composite markers developed to predict chronological age or mortality risk from DNA methylation (DNAm) data. The present study investigated the associations between 4 epigenetic clocks (Horvath’s and Hannum’s DNAmAge and DNAm GrimAge and PhenoAge) and physical functioning during a 3-year follow-up. Method We studied 63- to 76-year-old women (N = 413) from the Finnish Twin Study on Aging. DNAm was measured from blood samples at baseline. Age acceleration (AgeAccel), that is, discrepancy between chronological age and DNAm age, was determined as residuals from linear model. Physical functioning was assessed under standardized laboratory conditions at b…
Additional file 3 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 3. Supplementary Figures - Figures S1-S31.
Do epigenetic clocks provide explanations for sex differences in lifespan? A cross-sectional twin study
ABSTRACTBackgroundThe sex gap in life expectancy has been narrowing in Finland over the past four to five decades; however, on average, women still live longer than men. Epigenetic clocks are markers for biological aging that predict lifespan. In this study, we examined the mediating role of lifestyle factors on the association between sex and biological aging in younger and older adults.MethodsOur sample included same-sex younger and older twins (21-42-y, n = 1110; 50-76-y, n = 763) and younger opposite-sex twins (21-30-y, n = 302). Blood-based DNA methylation (DNAm) was used to compute epigenetic age acceleration by four epigenetic clocks as a measure of biological aging. Path modelling w…
The Older Finnish Twin Cohort : 45 Years of Follow-up
AbstractThe older Finnish Twin Cohort (FTC) was established in 1974. The baseline survey was in 1975, with two follow-up health surveys in 1981 and 1990. The fourth wave of assessments was done in three parts, with a questionnaire study of twins born during 1945–1957 in 2011–2012, while older twins were interviewed and screened for dementia in two time periods, between 1999 and 2007 for twins born before 1938 and between 2013 and 2017 for twins born in 1938–1944. The content of these wave 4 assessments is described and some initial results are described. In addition, we have invited twin-pairs, based on response to the cohortwide surveys, to participate in detailed in-person studies; these …
Leisure-time physical activity and DNA methylation age : a twin study
Background: Epigenetic clocks may increase our understanding on human aging and how genetic and environmental factors regulate an individual aging process. One of the most promising clocks is Horvath’s DNA methylation (DNAm) age. Age acceleration, i.e., discrepancy between DNAm age and chronological age, tells us whether the person is biologically young or old compared to his/her chronological age. Several environmental and lifestyle factors have been shown to affect life span. We investigated genetic and environmental predictors of DNAm age in young and older monozygotic (MZ) and dizygotic (DZ) twins with a focus on leisure time physical activity. Results: Quantitative genetic modeling rev…
Additional file 6 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 6. Review history.
Does the epigenetic clock GrimAge predict mortality independent of genetic influences : an 18 year follow-up study in older female twin pairs
Background: Epigenetic clocks are based on DNA methylation (DNAm). It has been suggested that these clocks are useable markers of biological aging and premature mortality. Because genetic factors explain variations in both epigenetic aging and mortality, this association could also be explained by shared genetic factors. We investigated the infuence of genetic and lifestyle factors (smoking, alcohol consumption, physical activity, chronic diseases, body mass index) and education on the association of accelerated epigenetic aging with mortality using a longitudinal twin design. Utilizing a publicly available online tool, we calculated the epigenetic age using two epigenetic clocks, Horvath D…
Additional file 1 of Blood and skeletal muscle ageing determined by epigenetic clocks and their associations with physical activity and functioning
Additional file 1: Within-pair correlations in age acceleration in blood and in muscle. Additional file 2: Associations between DNAmAge age acceleration estimates and body composition and physical activity in blood. Additional file 3: Sensitivity analyses related to twin pair discordance in body mass index.
Leisure-Time and Occupational Physical Activity Associates Differently with Epigenetic Aging
Supplemental digital content is available in the text.
Do Epigenetic Clocks Provide Explanations for Sex Differences in Life Span? A Cross-Sectional Twin Study
Abstract Background The sex gap in life expectancy has been narrowing in Finland over the past 4–5 decades; however, on average, women still live longer than men. Epigenetic clocks are markers for biological aging which predict life span. In this study, we examined the mediating role of lifestyle factors on the association between sex and biological aging in younger and older adults. Methods Our sample consists of younger and older twins (21‒42 years, n = 1 477; 50‒76 years, n = 763) including 151 complete younger opposite-sex twin pairs (21‒30 years). Blood-based DNA methylation was used to compute epigenetic age acceleration by 4 epigenetic clocks as a measure of biological aging. Path mo…
Additional file 1 of Blood and skeletal muscle ageing determined by epigenetic clocks and their associations with physical activity and functioning
Additional file 1: Within-pair correlations in age acceleration in blood and in muscle. Additional file 2: Associations between DNAmAge age acceleration estimates and body composition and physical activity in blood. Additional file 3: Sensitivity analyses related to twin pair discordance in body mass index.
Mutations in the β-tropomyosin (TPM2) gene – a rare cause of nemaline myopathy
Nemaline myopathy is a clinically and genetically heterogeneous muscle disorder. In the nebulin gene we have detected a number of autosomal recessive mutations. Both autosomal dominant and recessive mutations have been detected in the genes for alpha -actin and alpha -tropomyosin 3. A recessive mutation causing nemaline myopathy among the Old Order Amish has recently been identified in the gene for slow skeletal muscle troponin T. As linkage studies had shown that at least one further gene exists for nemaline myopathy, we investigated another tropomyosin gene expressed in skeletal muscle, the beta -tropomyosin 2 gene. Screening 66 unrelated patients, using single strand conformation polymor…
Additional file 5 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 5. Colocalization plots.
Additional file 1 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 1. Individual cohort descriptions and acknowledgements.
Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study
Nicotinamide adenine dinucleotide (NAD + ) precursor nicotinamide riboside (NR) has emerged as a promising compound to improve obesity-associated mitochondrial dysfunction and metabolic syndrome in mice. However, most short-term clinical trials conducted so far have not reported positive outcomes. Therefore, we aimed to determine whether long-term NR supplementation boosts mitochondrial biogenesis and metabolic health in humans. Twenty body mass index (BMI)–discordant monozygotic twin pairs were supplemented with an escalating dose of NR (250 to 1000 mg/day) for 5 months. NR improved systemic NAD + metabolism, muscle mitochondrial number, myoblast differentiation, and gut microbiota compos…
Additional file 5 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 5. Colocalization plots.
Additional file 6 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 6. Review history.
Genome-wide association studies identify 137 loci for DNA methylation biomarkers of ageing
AbstractBiological ageing estimators derived from DNA methylation (DNAm) data are heritable and correlate with morbidity and mortality. Leveraging DNAm and SNP data from >41,000 individuals, we identify 137 genome-wide significant loci (113 novel) from meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We report strong genetic correlations with longevity and lifestyle factors such as smoking, education, and obesity. Significant associations are observed in polygenic risk score analysis and to a lesser extent in Mendelian randomization analyses. This study illuminates the genetic …
Mortality associations with DNA methylation-based biological aging and physical functioning measures across a 20-year follow-up period
Background Measures of biological aging range from DNA methylation (DNAm)-based estimates to measures of physical abilities. The purpose of this study was to compare DNAm- and physical functioning-based measures of biological aging in predicting mortality. Methods We studied 63- to 76-year-old women (N = 395) from the Finnish Twin Study on Aging (FITSA). Participants’ biological age (epigenetic clocks DNAm GrimAge and DunedinPACE) was estimated using blood DNAm data. Tests of physical functioning conducted under standardized laboratory conditions included the Timed Up and Go (TUG) test and 10-m walk test. Mortality hazard ratios (HRs) were calculated per every one standard deviation (SD) in…
The role of adolescent lifestyle habits in biological aging: A prospective twin study
Adolescence is a stage of fast growth and development. Exposures during puberty can have long-term effects on health in later life. This study aims to investigate the role of adolescent lifestyle in biological aging.The study participants originated from the longitudinal FinnTwin12 study (n = 5114). Adolescent lifestyle-related factors, including body mass index (BMI), leisure-time physical activity, smoking, and alcohol use, were based on self-reports and measured at ages 12, 14, and 17 years. For a subsample, blood-based DNA methylation (DNAm) was used to assess biological aging with six epigenetic aging measures in young adulthood (21-25 years, n = 824). A latent class analysis was condu…
Methylation status of VTRNA2-1/nc886 is stable across populations, monozygotic twin pairs and in majority of tissues.
Aims & methods: The aim of this study was to characterize the methylation level of a polymorphically imprinted gene, VTRNA2-1/nc886, in human populations and somatic tissues.48 datasets, consisting of more than 30 tissues and >30,000 individuals, were used. Results: nc886 methylation status is associated with twin status and ethnic background, but the variation between populations is limited. Monozygotic twin pairs present concordant methylation, whereas similar to 30% of dizygotic twin pairs present discordant methylation in the nc886 locus. The methylation levels of nc886 are uniform across somatic tissues, except in cerebellum and skeletal muscle. Conclusion: The nc886 imprint may be est…
Blood and skeletal muscle ageing determined by epigenetic clocks and their associations with physical activity and functioning
AbstractThe aim of this study was to investigate the correspondence of different biological ageing estimates (i.e. epigenetic age) in blood and muscle tissue and their associations with physical activity (PA), physical function and body composition. Two independent cohorts (N = 139 and N = 47) were included, whose age span covered adulthood (23–69 years). Whole blood and m. vastus lateralis samples were collected, and DNA methylation was analysed. Four different DNA methylation age (DNAmAge) estimates were calculated using genome-wide methylation data and publicly available online tools. A novel muscle-specific methylation age was estimated using the R-package ‘MEAT’. PA was measured with q…
Methylation status of VTRNA2-1/nc886 is stable across populations, monozygotic twin pairs and in majority of tissues. Supplementary data
Supplementary Table 1. This study used 48 DNA methylation datasets, including DILGOM, FTC, ERMA, KORA, LURIC, NELLI, SATSA and YFS as well as 39 datasets available in the Gene Expression Omnibus (GEO) [29] consisting of >30 tissues and >30,000 individuals. Supplementary Table 2. Differences in the proportion of individuals with imprinted nc886 locus between sexes or in a case–control setting. Supplementary Table 3. Of these discordant pairs, one co-twin was always intermediately methylated, whereas the other co-twin was either imprinted or nonmethylated in all cases – that is, no twin pairs were identified in which one co-twin was imprinted and the other was nonmethylated. Supplementa…
Additional file 2 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 2. Supplementary Tables -Tables S1-S31.
Additional file 2 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 2. Supplementary Tables -Tables S1-S31.