<scp>DNA</scp>
            methylation age is associated with mortality in a longitudinal Danish twin study

Christiansen, Lene; Lénárt, Ádám; Tan, Qihua; Vaupel, James W.; Aviv, Abraham; McGue, Matt; Christensen, Kaare

doi:10.1111/acel.12421

Cited by 258 publications

(202 citation statements)

References 26 publications

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“…To date, two studies have described significant associations between DNAm-age and all-cause mortality [29, 33]. Moreover, studies have also demonstrated that DNAm-age may predict or be reflective of various disease processes [31, 32, 34–37].…”

Section: Discussionmentioning

confidence: 99%

Long-term ambient particle exposures and blood DNA methylation age: findings from the VA normative aging study

et al. 2016

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BackgroundAmbient particles have been shown to exacerbate measures of biological aging; yet, no studies have examined their relationships with DNA methylation age (DNAm-age), an epigenome-wide DNA methylation based predictor of chronological age.ObjectiveWe examined the relationship of DNAm-age with fine particulate matter (PM2.5), a measure of total inhalable particle mass, and black carbon (BC), a measure of particles from vehicular traffic.MethodsWe used validated spatiotemporal models to generate 1-year PM2.5 and BC exposure levels at the addresses of 589 older men participating in the VA Normative Aging Study with 1–3 visits between 2000 and 2011 (n = 1032 observations). Blood DNAm-age was calculated using 353 CpG sites from the Illumina HumanMethylation450 BeadChip. We estimated associations of PM2.5 and BC with DNAm-age using linear mixed effects models adjusted for age, lifestyle/environmental factors, and aging-related diseases.ResultsAfter adjusting for covariates, a 1-µg/m3 increase in PM2.5 (95% CI: 0.30, 0.75, P<0.0001) was significantly associated with a 0.52-year increase in DNAm-age. Adjusted BC models showed similar patterns of association (β = 3.02, 95% CI: 0.48, 5.57, P = 0.02). Only PM2.5 (β = 0.54, 95% CI: 0.24, 0.84, P = 0.0004) remained significantly associated with DNAm-age in two-particle models. Methylation levels from 20 of the 353 CpGs contributing to DNAm-age were significantly associated with PM2.5 levels in our two-particle models. Several of these CpGs mapped to genes implicated in lung pathologies including LZTFL1, PDLIM5, and ATPAF1.ConclusionOur results support an association of long-termambient particle levels with DNAm-age and suggest that DNAm-age is a biomarker of particle-related physiological processes.

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Section: Discussionmentioning

confidence: 99%

Long-term ambient particle exposures and blood DNA methylation age: findings from the VA normative aging study

et al. 2016

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“…The resultant DNA methylation‐based predicted age ( i.e ., DNAm age) was associated with chronological age in several independent studies. The difference between DNAm age and chronological age ( i.e ., DNAm Δage) has been proposed as an index of accelerated aging and was reported to be associated with all‐cause mortality and several coronary heart disease risk factors (Marioni et al ., 2015; Christiansen et al ., 2016; Horvath et al ., 2016). …”

Section: Introductionmentioning

confidence: 99%

Age‐associated microRNA expression in human peripheral blood is associated with all‐cause mortality and age‐related traits

et al. 2017

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SummaryRecent studies provide evidence of correlations of DNA methylation and expression of protein‐coding genes with human aging. The relations of microRNA expression with age and age‐related clinical outcomes have not been characterized thoroughly. We explored associations of age with whole‐blood microRNA expression in 5221 adults and identified 127 microRNAs that were differentially expressed by age at P < 3.3 × 10−4 (Bonferroni‐corrected). Most microRNAs were underexpressed in older individuals. Integrative analysis of microRNA and mRNA expression revealed changes in age‐associated mRNA expression possibly driven by age‐associated microRNAs in pathways that involve RNA processing, translation, and immune function. We fitted a linear model to predict ‘microRNA age’ that incorporated expression levels of 80 microRNAs. MicroRNA age correlated modestly with predicted age from DNA methylation (r = 0.3) and mRNA expression (r = 0.2), suggesting that microRNA age may complement mRNA and epigenetic age prediction models. We used the difference between microRNA age and chronological age as a biomarker of accelerated aging (Δage) and found that Δage was associated with all‐cause mortality (hazards ratio 1.1 per year difference, P = 4.2 × 10−5 adjusted for sex and chronological age). Additionally, Δage was associated with coronary heart disease, hypertension, blood pressure, and glucose levels. In conclusion, we constructed a microRNA age prediction model based on whole‐blood microRNA expression profiling. Age‐associated microRNAs and their targets have potential utility to detect accelerated aging and to predict risks for age‐related diseases.

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“…This epigenetic clock method for estimating age is highly correlated with chronological age across cell types and complex tissues(26;29;30). The epigenetic clock is thought to capture aspects of biological age, supported by data demonstrating that the older epigenetic age of blood is predictive of all-cause mortality(31;32), younger epigenetic age relates to cognitive and physical fitness in the elderly(33), and epigenetic age is younger in the offspring of Italian semi-supercentenarians (i.e. subjects aged 105 or older) compared to age-matched controls(34).…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Aging and Immune Senescence in Women With Insomnia Symptoms: Findings From the Women’s Health Initiative Study

Carroll¹,

Irwin²,

Levine³

et al. 2017

Biological Psychiatry

114

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BACKGROUND Insomnia symptoms are associated with vulnerability to age-related morbidity and mortality. Cross-sectional data suggest accelerated biological aging may be a mechanism through which sleep influences risk. A novel method for determining age acceleration using epigenetic methylation to DNA has demonstrated predictive utility as an epigenetic clock and prognostic of age-related morbidity and mortality. METHODS We examined the association of epigenetic age and immune cell aging with sleep in the Women’s Health Initiative (WHI) study (N=2,078; Age M(SD)=64.5(7.1) with assessment of insomnia symptoms (restlessness, difficulty falling asleep, waking at night, trouble getting back to sleep, and early awakenings), sleep duration (short-sleep 5 or less; long-sleep >8hrs), epigenetic age, naïve T cell (CD8+CD45RA+CCR7+), and late differentiated T cells (CD8+CD28−CD45RA−). RESULTS Insomnia symptoms were related to advanced epigenetic age, B(SE)=1.02(.37), P=0.005, after adjustments for covariates. Insomnia symptoms were also associated with more late differentiated T cells (B(SE)=.59(.21), P=.006), but not with naïve T cells. Self-reported short and long sleep duration were unrelated to epigenetic age. Short sleep, but not long sleep, was associated with fewer naïve T cells (P<.005) and neither were related to late differentiated T cells. CONCLUSIONS Symptoms of insomnia were associated with increased epigenetic age of blood tissue, and were associated with higher counts of late differentiated CD8+ T cells. Short sleep was unrelated to epigenetic age and late differentiated cell counts, but was related to a decline in naïve T cells. In this large population based study of women in the United States, insomnia symptoms are implicated in accelerated aging.

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DNA methylation age is associated with mortality in a longitudinal Danish twin study

Cited by 258 publications

References 26 publications

Long-term ambient particle exposures and blood DNA methylation age: findings from the VA normative aging study

Long-term ambient particle exposures and blood DNA methylation age: findings from the VA normative aging study

Age‐associated microRNA expression in human peripheral blood is associated with all‐cause mortality and age‐related traits

Epigenetic Aging and Immune Senescence in Women With Insomnia Symptoms: Findings From the Women’s Health Initiative Study

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