Clinical Epigenetics

BackgroundSmoking is a major preventable risk factor for all-cause mortality and disability worldwide. It leads to age-related diseases, but the effects and reversibility of smoking behaviors on different epigenetic clocks are not fully explored. ObjectiveTo characterize the association of epigenetic age acceleration in whole blood with active and secondhand smoking (SHS), smoking intensity, and time since cessation among U.S. adults. MethodsThis is a cross-sectional study in adults from the N...

Study questionIs DNA methylation at birth associated with having been conceived by assisted reproductive technologies (ART)? Summary answerThis study shows does not provide strong evidence of an association of conception by ART with variation in infant blood cell DNA methylation. What is known alreadyAssisted reproductive technologies (ART) are procedures used to help infertile/subfertile couples conceive. Due to its importance in gene regulation during early development programming, DNA methy...

Epigenetic clocks and scores have been investigated as potential biomarkers of later-life health outcomes following early-life exposures. In pediatric settings, DNA methylation (DNAm) is often measured in saliva; however, most clocks and scores have been trained in adult blood. Therefore, we assessed the performance, correlation, longitudinal stability, and association with early-life adversity (ELA) for established epigenetic measures in matched pediatric blood and saliva samples. Leveraging th...

Research on maternal-fetal epigenetic programming argues that adverse exposures to the intrauterine environment can have long-term effects on adult morbidity and mortality. However, causal research on epigenetic programming in humans at a population level is rare and is often unable to separate intrauterine effects from conditions in the postnatal period that may continue to impact child development. In this study, we used a quasi-natural experiment that leverages state-year variation in economi...

Social determinants of health are social factors that affect health and survival. Two of the most powerful social determinants are socioeconomic status (SES) and race/ethnicity; people with lower SES or marginalized race/ethnicity tend to experience earlier onset of aging-related diseases and have shorter lifespans. DNA methylation (DNAm) measures of biological aging, often referred to as "epigenetic clocks", are increasingly used to study the social determination of health. However, there are s...

BackgroundBiological aging begins decades before the onset of age-related clinical conditions and is mediated by both cellular senescence and declining adaptive immune function. These processes are functionally related with the rate of senescent cell accumulation dependent upon a balance between induction and immune clearance. We previously showed that biomarkers in these domains can identify patients at-risk of surgery-related adverse events. Here, we describe evidence of clinical relevance in ...

BackgroundDNA methylation-based biological age (DNAm age) is potentially an important biomarker for adult health. Studies in specific age ranges have found widely varying results about its causes of variation. We investigated these causes across the lifespan. MethodsWe pooled genome-wide DNA methylation data for 4,217 people aged 0-92 years from 1,871 families. DNAm age was calculated using the Horvath epigenetic clock. We estimated familial correlations in DNAm age for monozygotic (MZ) twin, d...

ImportancePeople who complete more education live longer lives with better health. New evidence suggests that these benefits operate through a slowed pace of biological aging. If so, measurements of the pace biological aging could offer intermediate endpoints for studies of how interventions to promote education will impact healthy longevity. ObjectiveTo test the hypothesis that upward educational mobility contributes to a slower pace of biological aging and increased longevity. DesignProspect...

IntroductionEarly-life adversity (ELA) encompasses a range of environmental stressors, including physical, emotional, and social challenges that can affect health during the critical early developmental period. Extensive research has linked ELA to negative long-term health outcomes, yet the underlying biological mechanisms remain poorly understood. The current study investigates how early institutional care changes the epigenetic landscape in young adults. The study also provides insights into r...

DNA methylation outlier burden has been suggested as a potential marker of biological age. An outlier is typically defined as DNA methylation levels at any one CpG site that are three times beyond the inter-quartile range from the 25th or 75th percentiles compared to the rest of the population. DNA methylation outlier burden (the number of such outlier sites per individual) increases exponentially with age. However, these findings have been observed in small samples. Here, we showed an associati...

Child maltreatment is a leading cause of pediatric morbidity and mortality, potentially propagated by DNA methylation (DNAm) changes. We conducted an EWAS meta-analysis (n=175, 554,979 Illumina EPICv1/EPICv2 sites) in buccal swabs from three hospital-based studies of children with traumatic injuries, stratified by study group to include 1) any traumatic injury, 2) fractures, and 3) traumatic brain injuries. Empirical bayes-moderated linear models tested differential DNAm with M-values, followed ...

Children of older fathers have higher risk for certain diseases. Nevertheless, how ageing specifically affects male germ cells is so far not completely understood. In a cohort of 197 healthy men (18-84 years), we found that semen and reproductive parameters remained normal over six decades. Along with an age-dependent increase in telomere length in sperm (r=0.41, p>0.001), we found accelerated DNA fragmentation, more prominent after the sixth decate of life, and with around 60% of men older than...

Fatty acids are involved in disease risk and aging processes. In the US National Health and Nutrition Examination Survey (1999-2002), we tested for associations of total, saturated (SFA), monounsaturated (MUFA), polyunsaturated (PUFA), and subtypes of dietary fatty acids with DNA methylation-based aging biomarkers, adjusting for age, BMI, total energy intake, and sociodemographic and behavioral factors (N=2,260). Higher SFA and MUFA were associated with greater GrimAge2, an aging biomarker of mo...

Manipulations to set back biological age and extend lifespan in animal models are well established, and translation to humans has begun. The length of human life makes it impractical to evaluate results by plotting mortality curves, so surrogate markers of age have been suggested and, at present, the best established surrogates are DNA methylation clocks. Herein we report on a randomized, controlled clinical trial designed to be a first step in evaluating the effect of a diet and lifestyle inter...

Prenatal exposure to trauma, including genocide and maternal rape, and adverse childhood experiences (ACEs), are associated with lifespan reduction. We evaluated whether prenatal exposure to genocide or genocidal rape, and ACEs among individuals conceived during the 1994 genocide against Tutsi in Rwanda were associated with differences in age acceleration in three first-generation (Horvath, Hannum, PhenoAge) and four second-generation epigenetic aging clocks (GrimAge, DunedinPace, YingDamAge, Yi...

ObjectiveSome evidence suggests that higher serum TSH may be a part of normal aging, but current studies are limited to 13-year follow-up. We examined TSH changes during 22 years of follow-up across the adult lifespan. DesignLongitudinal analyses of the population-based HUNT Study in Norway, with TSH measurements from 1995-97, 2006-08 and 2017-19. MethodsIn the overall population and in individuals without thyroid medication or disease, we estimated i) geometric mean serum TSH by age, integrat...

Calorie restriction (CR) slows aging and increases healthy lifespan in model organisms. We tested if CR slowed biological aging in humans using DNA methylation analysis of blood samples from N=197 participants in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) randomized controlled trial. We quantified CR effects on biological aging by comparing change scores for six epigenetic-clock and Pace-of-Aging measures between n=128 CR-group and n=69 ad-libitum-co...

Cellular senescence and DNA methylation are primary aging mechanisms emerging as a potential means of monitoring human aging and evaluating interventions thought to either accelerate or slow an individuals aging trajectory. However, it is largely unknown whether cellular senescence and signatures of methylation of the specific CpG islands that comprise various epigenetic clocks correlate in humans. We have measured the cellular senescence biomarker, p16 and the five most used epigenetic aging cl...

The prevalence of many diseases differs by sex, potentially due to sex-specific patterns in DNA methylation. Autosomal sex-specific differences in DNA methylation have been observed in cord blood and placental tissue, but are not well studied in saliva or in diverse populations. We sought to characterize sex-specific DNA methylation on autosomal chromosomes in saliva samples from children in the Fragile Families and Child Wellbeing Study, a multi-ethnic prospective birth cohort containing an ove...

ABSTRACTThe pace of aging varies between individuals and is marked by changes in DNA methylation (DNAm) including an increase in randomness or entropy. Here, we computed epigenetic scores of aging and entropy using DNAm datasets from the Womens Health Initiative (WHI). We investigated how different epigenetic aging metrics relate to demographic and health variables, and mortality risk. Income and education, two proxies of socioeconomics (SE), had consistent associations with epigenetic aging and...