Publications by authors named "Julia MacIsaac"

Cheek swabs, heterogeneous samples consisting primarily of buccal epithelial cells, are widely used in pediatric DNA methylation studies and biomarker creation. However, the decrease in buccal proportion with age in adults remains unexamined in childhood. We analyzed cheek swabs from 4626 typically developing children 2-months to 20-years-old.

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Saliva is a widely used sample in epigenetic research with children due to its non-invasive nature. Since DNA methylation (DNAm) profile is cell type (CT) specific, salivary DNAm associations with exposures may be influenced by CT compositions, which is highly variable in saliva as it contains immune and buccal epithelial cells (BEC). Reference-based CT deconvolution and statistically adjusting estimated CT in DNAm analyses have become an increasingly common practice.

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  • * The study assesses the effects of prenatal and postnatal stress and depression on DNA methylation in newborns and 12-month-old children using the CHILD cohort, measuring stress and depression at multiple time points.
  • * Results showed significant associations between both prenatal and postnatal stress/depression and changes in DNA methylation at specific CpG sites in the newborn's cord blood and in blood from 12-month-old children, suggesting a biological impact of maternal mental health on child development.
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We examined whether prenatal exposure to two classes of endocrine-disrupting chemicals (EDCs) was associated with infant epigenetic age acceleration (EAA), a DNA methylation biomarker of aging. Participants included 224 maternal-infant pairs from a Canadian pregnancy cohort study. Two bisphenols and 12 phthalate metabolites were measured in maternal second trimester urines.

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Early-life adversity increases the risk of health problems. Interventions supporting protective and responsive caregiving offer a promising approach to attenuating adversity-induced changes in stress-sensitive biomarkers. This study tested whether participation in an evidence-based dyadic psychosocial intervention, child-parent psychotherapy (CPP), was related to lower epigenetic age acceleration, a trauma-sensitive biomarker of accelerated biological aging that is associated with later health impairment, in a sample of children with trauma histories.

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  • The Illumina MethylationEPIC BeadChip microarray platform has two versions (v1.0 and v2.0), which show high correlation overall but varying results at the probe level for tools assessing DNA methylation effects.
  • Research using blood samples from different adult age groups found that samples clustered more by the EPIC version used than by other characteristics, indicating significant differences in data outputs between the two versions.
  • The study emphasizes the need to consider which EPIC version is used when analyzing data for meta-analyses and longitudinal studies, as these differences can impact findings in epigenome-wide association studies (EWAS).
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Objective: Youth-onset type 2 diabetes (T2D) is physiologically distinct from adult-onset, but it is not clear how the two diseases differ at a molecular level. In utero exposure to maternal type 2 diabetes (T2D) is known to be a specific risk factor for youth-onset T2D. DNA methylation (DNAm) changes associated with T2D but which differ between youth- and adult-onset might delineate the impacts of T2D development at different ages and could also determine the contribution of exposure to in utero diabetes.

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  • The study investigates how inhaled corticosteroids (ICS) affect gene expression in healthy airways, ensuring that results are not influenced by pre-existing disease conditions.
  • A randomized trial involved 30 healthy adults receiving either high-dose fluticasone or no treatment for 4 weeks, with lung samples analyzed for immunological changes.
  • Results showed that ICS treatment reduced various genes tied to immune responses, indicating that healthy airways maintain a delicate balance of immune signaling that can be significantly altered by ICS use.
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  • Previous research links living in disadvantaged neighborhoods to poor health, potentially affecting inflammation and immune responses through epigenetic changes like DNA methylation (DNAm).
  • The study utilized robust linear regression models to analyze the association between neighborhood deprivation and DNAm in brain tissue from 159 donors, identifying one significant CpG site (cg26514961) linked to neighborhood deprivation.
  • Notably, the study found that the association was more pronounced in individuals with at least one ε4 allele, with some CpG sites showing agreement between brain tissue and easily accessible tissues, suggesting their potential as biomarkers for studying health effects in living individuals.
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Background: Evidence suggests that prenatal air pollution exposure alters DNA methylation (DNAm), which could go on to affect long-term health. It remains unclear whether DNAm alterations present at birth persist through early life. Identifying persistent DNAm changes would provide greater insight into the molecular mechanisms contributing to the association of prenatal air pollution exposure with atopic diseases.

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Maternal stress and depression during pregnancy and the first year of the infant's life affect a large percentage of mothers. Maternal stress and depression have been associated with adverse fetal and childhood outcomes as well as differential child DNA methylation (DNAm). However, the biological mechanisms connecting maternal stress and depression to poor health outcomes in children are still largely unknown.

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Caloric restriction (CR) modifies lifespan and aging biology in animal models. The Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE™) 2 trial tested translation of these findings to humans. CALERIE™ randomized healthy, nonobese men and premenopausal women (age 21-50y; BMI 22.

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Di(2-ethylhexyl) phthalate (DEHP) is a common plasticizer that can affect immune system development and susceptibility to infection. Aging processes (measured as epigenetic age acceleration (EAA)) may mediate the immune-related effects of prenatal exposure to DEHP. This study's objective was to examine associations between prenatal DEHP exposure, EAA at three months of age, and the number of upper respiratory infections (URIs) from 12 to 18 months of age using a sample of 69 maternal-child pairs from a Canadian pregnancy cohort.

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Background: While ageing is associated with increased insulin resistance (IR), the molecular mechanisms underlying increased IR in the muscle, the primary organ for glucose clearance, have yet to be elucidated in older individuals. As epigenetic processes are suggested to contribute to the development of ageing-associated diseases, we investigated whether differential DNA methylation was associated with IR in human primary muscle stem cells (myoblasts) from community-dwelling older individuals.

Methods: We measured DNA methylation (Infinium HumanMethylationEPIC BeadChip) in myoblast cultures from vastus lateralis biopsies (119 males/females, mean age 78.

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Background: Socioeconomic status (SES) gradients in health are well-documented, and while biological pathways are incompletely understood, chronic inflammation and accelerated immune aging (immunosenescence) among lower SES individuals have been implicated. However, previous findings have come from samples in higher income countries, and it is unclear how generalizable they are to lower- and middle-income countries (LMIC) with different infectious exposures and where adiposity-an important contributor to chronic inflammation-might show different SES patterning. To address this gap, we explored associations between SES and inflammation and immunosenescence in a sample of women in Cebu, Philippines.

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Background: In the first year of life, DNA methylation (DNAm) patterns are established and are particularly susceptible to exposure-induced changes. Some of these changes may leave lasting effects by persistently altering gene expression or cell type composition or function, contributing to disease.

Objectives: In this discovery study, we investigated DNAm associations with sensitization to peanut, egg, or cow's milk and hypothesized that genes demonstrating DNAm differences in immune cells may play a role in the development of food sensitization.

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Household air pollution caused by inefficient cooking practices causes 4 million deaths a year worldwide. In Nepal, 86% of the rural population use solid fuels for cooking. Over 25% of premature deaths associated with air pollution are respiratory in nature.

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Article Synopsis
  • This study explores how early-life infectious exposures may influence biological aging, using DNA methylation markers to assess changes that affect future health and life expectancy.
  • The research analyzed data from 1,450 participants in a long-term health survey, focusing on their health during infancy and how that links to biological aging in their young adulthood.
  • Results indicated that higher early-life infection rates and certain birth conditions were linked to slower biological aging, suggesting a complex relationship between early infections and long-term health outcomes that needs further investigation.
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  • Epigenetic modifications are prevalent in COPD, and this study examines their relationship with patient symptoms and health status using DNA methylation analysis of blood and airway samples.
  • A total of 29,211 differentially methylated positions (DMPs) in blood and 5044 in airways were linked to health status as measured by the St. George's Respiratory Questionnaire (SGRQ).
  • The findings suggest a strong connection between epigenetic changes and COPD-related co-morbidities, indicating that blood samples may be a valuable source for identifying potential biomarkers for assessing clinical outcomes in COPD.
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One of the proposed mechanisms linking childhood stressor exposure to negative mental and physical health outcomes in later life is cellular aging. In this prospective, longitudinal, and pre-registered study, we examined the association between a cumulative pattern of childhood risk exposure from age 6 to age 10 (i.e.

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Evolutionary-developmental psychologists have posited that individuals who grow up in stressful rearing circumstances follow faster life history strategies, thereby increasing their chances of reproduction. This preregistered study tested this stress-acceleration hypothesis in a low-risk longitudinal sample of 193 Dutch mother-child dyads, by investigating whether infant-mother attachment insecurity at 12 months of age predicted earlier pubertal onset and more callous-unemotional traits, aggression and risk-taking about a decade later. Also evaluated were the possible mediating roles of two biomarkers of accelerated aging (i.

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Epigenetic changes are required for normal development, yet the nature and respective contribution of factors that drive epigenetic variation in humans remain to be fully characterized. Here, we assessed how the blood DNA methylome of 884 adults is affected by DNA sequence variation, age, sex and 139 factors relating to life habits and immunity. Furthermore, we investigated whether these effects are mediated or not by changes in cellular composition, measured by deep immunophenotyping.

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Background: Age-related comorbidities such as chronic obstructive pulmonary disease (COPD) are common in people living with human immunodeficiency virus (PLWH). We investigated the relationship between COPD and the epigenetic age of the airway epithelium and peripheral blood of PLWH.

Methods: Airway epithelial brushings from 34 PLWH enrolled in the St.

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Article Synopsis
  • Epigenetic clocks track changes in DNA methylation linked to aging and can predict health outcomes, with this study focusing on the relationship between fetal nutrition and accelerated biological aging in young adults.* -
  • Data from the Cebu Longitudinal Health and Nutrition Survey (CLHNS) highlighted that lower birth weight in males was associated with advanced biological aging using various epigenetic clocks, while no such prediction was made for females.* -
  • The study indicates that epigenetic clocks could be useful for assessing long-term health impacts of fetal growth, emphasizing the importance of sex differences in these outcomes.*
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