The pediatric buccal epigenetic clock identifies significant ageing acceleration in children with internalizing disorder and maltreatment exposure

Abstract Background Patterns of methylation influence lifespan, but methylation and lifespan may also depend on diet, or differ between genotypes. Prior to this study, interactions between diet and genotype have not been explored together to determine their influence on methylation. The invertebrate Daphnia magna is an excellent choice for testing the epigenetic response to the environment: parthenogenetic offspring are identical to their siblings (making for powerful genetic comparisons), they are relatively short lived and have well-characterised inter-strain life-history trait differences. We performed a survival analysis in response to caloric restriction and then undertook a 47-replicate experiment testing the DNA methylation response to ageing and caloric restriction of two strains of D. magna. Results Methylated cytosines (CpGs) were most prevalent in exons two to five of gene bodies. One strain exhibited a significantly increased lifespan in response to caloric restriction, but there was no effect of food-level CpG methylation status. Inter-strain differences dominated the methylation experiment with over 15,000 differently methylated CpGs. One gene, Me31b, was hypermethylated extensively in one strain and is a key regulator of embryonic expression. Sixty-one CpGs were differentially methylated between young and old individuals, including multiple CpGs within the histone H3 gene, which were hypermethylated in old individuals. Across all age-related CpGs, we identified a set that are highly correlated with chronological age. Conclusions Methylated cytosines are concentrated in early exons of gene sequences indicative of a directed, non-random, process despite the low overall DNA methylation percentage in this species. We identify no effect of caloric restriction on DNA methylation, contrary to our previous results, and established impacts of caloric restriction on phenotype and gene expression. We propose our approach here is more robust in invertebrates given genome-wide CpG distributions. For both strain and ageing, a single gene emerges as differentially methylated that for each factor could have widespread phenotypic effects. Our data showed the potential for an epigenetic clock at a subset of age positions, which is exciting but requires confirmation.

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Epigenetic clock and methylation study of oocytes from a bovine model of reproductive aging

Aging Cell ◽

10.1111/acel.13349 ◽

2021 ◽

Author(s):

Paweł Kordowitzki ◽

Amin Haghani ◽

Joseph A. Zoller ◽

Caesar Z. Li ◽

Ken Raj ◽

...

Keyword(s):

Epigenetic Clock ◽

Reproductive Aging

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Recalibrating the epigenetic clock after exposure to trauma: The role of risk and protective psychosocial factors

Journal of Psychiatric Research ◽

10.1016/j.jpsychires.2021.11.026 ◽

2021 ◽

Author(s):

Divya Mehta ◽

Dagmar Bruenig ◽

John Pierce ◽

Anita Sathyanarayanan ◽

Rachel Stringfellow ◽

...

Keyword(s):

Psychosocial Factors ◽

Epigenetic Clock ◽

Exposure To Trauma

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Relationship between five Epigenetic Clocks, Telomere Length and Functional Capacity assessed in Older Adults: Cross-sectional and Longitudinal Analyses

10.1101/2021.10.05.21264547 ◽

2021 ◽

Author(s):

Valentin Max Vetter ◽

Christian Humberto Kalies ◽

Yasmine Sommerer ◽

Dominik Spira ◽

Johanna Drewelies ◽

...

Keyword(s):

Telomere Length ◽

Time Course ◽

Nutritional Assessment ◽

Depression Scale ◽

Mini Nutritional Assessment ◽

Epigenetic Clock ◽

Cross Sectional ◽

Biomarkers Of Aging ◽

Functional Assessments

AbstractDNA methylation age acceleration (DNAmAA, derived from an epigenetic clock) and relative leukocyte telomere length (rLTL) are widely accepted biomarkers of aging. Nevertheless, it is still unclear which aspects of aging they represent best. Here we evaluated longitudinal associations between baseline rLTL and DNAmAA (estimated with 7-CpG clock) and functional assessments covering different domains of aging. Additionally, we made use of cross-sectional data on these assessments and examined their association with DNAmAA estimated by five different DNAm age measures.Two-wave longitudinal data was available for 1,083 participants of the Berlin Aging Study II (BASE-II) who were re-examined on average 7.4 years after baseline as part of the GendAge study. Functional outcomes were assessed with Fried’s frailty score, Tinetti mobility test, falls in the past 12 months (yes/no), Finger-floor distance, Mini Mental State Examination (MMSE), Center for Epidemiologic Studies Depression Scale (CES-D), Activities of Daily Living (ADL), Instrumented ADL (IADL) and Mini Nutritional Assessment (MNA).Overall, we found no evidence for an association between the molecular biomarkers measured at baseline, rLTL and DNAmAA (7-CpG clock), and functional assessments assessed at follow-up. Similarly, a cross-sectional analyses of follow-up data did also not show evidence for associations of the various DNAmAA measures (7-CpG clock, Horvath’s clock, Hannum’s clock PhenoAge, and GrimAge) with functional assessments.In conclusion, neither rLTL nor 7-CpG DNAmAA were able to predict impairment in the analyzed assessments over a ∼7 year time-course. Similarly, DNAmAA as estimated by five epigenetic clocks was not a good cross-sectional marker of health deterioration either.

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An epigenetic predictor of death captures multi-modal measures of brain health

10.1101/703504 ◽

2019 ◽

Cited By ~ 5

Author(s):

Robert F. Hillary ◽

Anna J. Stevenson ◽

Simon R. Cox ◽

Daniel L. McCartney ◽

Sarah E. Harris ◽

...

Keyword(s):

Cognitive Ability ◽

Epigenetic Mechanism ◽

Vascular Lesions ◽

Epigenetic Clock ◽

General Cognitive Ability ◽

Brain Health ◽

Standard Deviation Increase ◽

Brain White Matter ◽

Age Related ◽

Lothian Birth Cohort

AbstractIndividuals of the same chronological age exhibit disparate rates of biological ageing. Consequently, a number of methodologies have been proposed to determine biological age and primarily exploit variation at the level of DNA methylation (DNAm) – a commonly studied epigenetic mechanism. A novel epigenetic clock, termed ‘DNAm GrimAge’ has outperformed its predecessors in predicting the risk of mortality as well as a number of age-related morbidities. However, the association between DNAm GrimAge and cognitive or neuroimaging phenotypes remains unknown. We explore these associations in the Lothian Birth Cohort 1936 (n=709, mean age 73 years). Higher DNAm GrimAge was strongly associated with all-cause mortality over twelve years of follow-up (Hazard Ratio per standard deviation increase in GrimAge: 1.81, P < 2.0 × 10-16). Higher DNAm GrimAge was associated with lower age 11 IQ (β=-0.11), lower age 73 general cognitive ability (β=-0.18), decreased brain volume (β=-0.25) and increased brain white matter hyperintensities (β=0.17). Sixty-eight of 137 health- and brain-related phenotypes tested were significantly associated with DNAm GrimAge. Adjusting all models for childhood cognitive ability attenuated to non-significance a small number of associations (12/68 associations; 6 of which were cognitive traits), but not the association with general cognitive ability (33.9% attenuation). Higher DNAm GrimAge cross-sectionally associates with lower cognitive ability and brain vascular lesions in older age, independently of early life cognitive ability. Thus, this epigenetic predictor of mortality is also associated with multiple different measures of brain health and may aid in the prediction of age-related cognitive decline.

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Epigenetic clocks reveal a rejuvenation event during embryogenesis followed by aging

10.1101/2021.03.11.435028 ◽

2021 ◽

Author(s):

Csaba Kerepesi ◽

Bohan Zhang ◽

Sang-Goo Lee ◽

Alexandre Trapp ◽

Vadim N. Gladyshev

Keyword(s):

Pluripotent Stem Cells ◽

Prenatal Development ◽

Biological Age ◽

Epigenetic Clock ◽

Ground Zero ◽

August Weismann ◽

Age Related ◽

Epigenetic Age ◽

Human Prenatal Development ◽

Changes Over Time

The notion that germline cells do not age goes back to the 19th century ideas of August Weismann. However, being in a metabolically active state, they accumulate damage and other age-related changes over time, i.e., they age. For new life to begin in the same young state, they must be rejuvenated in the offspring. Here, we developed a new multi-tissue epigenetic clock and applied it, together with other aging clocks, to track changes in biological age during mouse and human prenatal development. This analysis revealed a significant decrease in biological age, i.e. rejuvenation, during early stages of embryogenesis, followed by an increase in later stages. We further found that pluripotent stem cells do not age even after extensive passaging and that the examined epigenetic age dynamics is conserved across species. Overall, this study uncovers a natural rejuvenation event during embryogenesis and suggests that the minimal biological age (the ground zero) marks the beginning of organismal aging.

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Epigenetic clock and DNA methylation studies of roe deer in the wild

10.1101/2020.09.21.306613 ◽

2020 ◽

Author(s):

Jean-François Lemaître ◽

Benjamin Rey ◽

Jean-Michel Gaillard ◽

Corinne Régis ◽

Emmanuelle Gilot ◽

...

Keyword(s):

Dna Methylation ◽

Evolutionary Biology ◽

Roe Deer ◽

Chronological Age ◽

Epigenetic Clock ◽

Aging Effects ◽

Methylation Array ◽

Biomarkers Of Aging ◽

Epigenetic Age ◽

The Relationship

AbstractDNA methylation-based biomarkers of aging (epigenetic clocks) promise to lead to new insights in the evolutionary biology of ageing. Relatively little is known about how the natural environment affects epigenetic aging effects in wild species. In this study, we took advantage of a unique long-term (>40 years) longitudinal monitoring of individual roe deer (Capreolus capreolus) living in two wild populations (Chizé and Trois Fontaines, France) facing different ecological contexts to investigate the relationship between chronological age and levels of DNA methylation (DNAm). We generated novel DNA methylation data from n=90 blood samples using a custom methylation array (HorvathMammalMethylChip40). We present three DNA methylation-based estimators of age (DNAm or epigenetic age), which were trained in males, females, and both sexes combined. We investigated how sex differences influenced the relationship between DNAm age and chronological age through the use of sex-specific epigenetic clocks. Our results highlight that both populations and sex influence the epigenetic age, with the bias toward a stronger male average age acceleration (i.e. differences between epigenetic age and chronological ages) particularly pronounced in the population facing harsh environmental conditions. Further, we identify the main sites of epigenetic alteration that have distinct aging patterns across the two sexes. These findings open the door to promising avenues of research at the crossroad of evolutionary biology and biogerontology.

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A New Monocyte Epigenetic Clock Reveals Effects of Alcohol Consumption on Epigenetic Aging in Three Independent Cohorts

10.1101/2021.03.22.436488 ◽

2021 ◽

Author(s):

Xiaoyu Liang ◽

Rajita Sinha ◽

Amy C. Justice ◽

Mardge H. Cohen ◽

Bradley E. Aouizerat ◽

...

Keyword(s):

Alcohol Consumption ◽

Hiv Infection ◽

Clinical Decision Making ◽

Clinical Decision ◽

Biological Age ◽

Biological Aging ◽

Epigenetic Clock ◽

Excessive Alcohol Consumption ◽

Epigenetic Age ◽

The Impact

AbstractBackgroundExcessive alcohol consumption increases the risk of aging-related comorbidities and mortality. Assessing the impact of alcohol consumption on biological age is important for clinical decision-making and prevention. Evidence shows that alcohol alters monocyte function, and age is associated with DNA methylome and transcriptomic changes among monocytes. However, no monocyte-based epigenetic clock is currently available. In this study, we developed a new monocyte-based DNA methylation clock (MonoDNAmAge) by using elastic net regularization. The MonoDNAmAge was validated by benchmarking using epigenetic age acceleration (EAA) in HIV infection. Using MonoDNAmAge clock as well as four established clocks (i.e., HorvathDNAmAge, HannumDNAmAge, PhenoDNAmAge, GrimDNAmAge), we then evaluated the effect of alcohol consumption on biological aging in three independent cohorts (N=2,242).ResultsMonoDNAmAge, comprised of 186 CpG sites, was highly correlated with chronological age (rtraining=0.96, p<2.20E-16; rtesting=0.86, p=1.55E-141). The MonoDNAmAge clock predicted an approximately 10-year age acceleration from HIV infection in two cohorts. Quadratic regression analysis showed a nonlinear relationship between MonoDNAmAge and alcohol consumption in the Yale Stress Center Community Study (YSCCS, pmodel=4.55E-08, px2 =7.80E-08) and in the Veteran Aging Cohort Study (VACS, pmodel=1.85E-02, px2 =3.46E-02). MonoDNAmAge and light alcohol consumption showed a negative linear relationship in the Women’s Interagency HIV Study (WIHS, β=-2.63, px=2.82E-06). Heavy consumption increased EAAMonoDNAmAge up to 1.60 years in the VACS while light consumption decreased EAAMonoDNAmAge to 2.66 years in the WIHS. These results were corroborated by the four established epigenetic clocks.ConclusionsWe observed a nonlinear effect of alcohol consumption on epigenetic age that is estimated by a novel monocyte-based “clock” in three distinct cohorts, highlighting the complex effects of alcohol consumption on biological age.

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Cardiovascular health is associated with the epigenetic clock in the Berlin Aging Study II (BASE-II)

Mechanisms of Ageing and Development ◽

10.1016/j.mad.2021.111616 ◽

2021 ◽

pp. 111616

Author(s):

Elisa Lemke ◽

Valentin Max Vetter ◽

Nora Berger ◽

Verena Laura Banszerus ◽

Maximilian König ◽

...

Keyword(s):

Cardiovascular Health ◽

Epigenetic Clock ◽

Aging Study

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