DNA methylation predicts age and provides insight into exceptional longevity of bats

AbstractExceptionally long-lived species, including many bats, rarely show overt signs of aging, making it difficult to determine why species differ in lifespan. Here, we use DNA methylation (DNAm) profiles from 712 known-age bats, representing 26 species, to identify epigenetic changes associated with age and longevity. We demonstrate that DNAm accurately predicts chronological age. Across species, longevity is negatively associated with the rate of DNAm change at age-associated sites. Furthermore, analysis of several bat genomes reveals that hypermethylated age- and longevity-associated sites are disproportionately located in promoter regions of key transcription factors (TF) and enriched for histone and chromatin features associated with transcriptional regulation. Predicted TF binding site motifs and enrichment analyses indicate that age-related methylation change is influenced by developmental processes, while longevity-related DNAm change is associated with innate immunity or tumorigenesis genes, suggesting that bat longevity results from augmented immune response and cancer suppression.

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Genome Methylation Predicts Age and Longevity of Bats

10.1101/2020.09.04.283655 ◽

2020 ◽

Cited By ~ 1

Author(s):

Gerald S. Wilkinson ◽

Danielle M. Adams ◽

Amin Haghani ◽

Ake T. Lu ◽

Joseph Zoller ◽

...

Keyword(s):

Dna Methylation ◽

Immune Response ◽

Chronological Age ◽

Methylation Change ◽

Epigenetic Changes ◽

Promoter Regions ◽

Age Related ◽

Genome Methylation ◽

Cancer Suppression ◽

Species Longevity

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Abstract 160: DNA-Methylation and Aging. Contribution of Biological Age to Recovery After Ischemic Stroke

Stroke ◽

10.1161/str.48.suppl_1.160 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Jordi Jimenez-Conde ◽

Carolina Soriano-Tarraga ◽

Eva Giralt-Steinhauer ◽

Marina Mola ◽

Rosa Vivanco-Hidalgo ◽

...

Keyword(s):

Dna Methylation ◽

Ischemic Stroke ◽

Functional Status ◽

Biological Age ◽

Chronological Age ◽

Bivariate Analysis ◽

Stroke Severity ◽

Age Related ◽

Recovery Capacity ◽

The Impact

Background: Stroke has a great impact in functional status of patients, although there are substantial interindividual differences in recovery capacity. Apart from stroke severity, age is considered an important predictor of outcome after stroke, but aging is not only due to chronological age. There are age-related DNA-methylation changes in multiple CpG sites across the genome that can be used to estimate the biological age (b-Age), and we seek to analyze the impact of this b-Age in recovery after an ischemic stroke. Methods: We include 600 individuals with acute ischemic stroke assessed in Hospital del Mar (Barcelona). Demographic and clinical data such as chronological age (c-Age), vascular risk factors, NIHSS at admission, recanalization treatment (rtPA or endovascular treatment), previous modified Rankin scale (p-mRS) and 3 months post stroke functional status (3-mRS) were registered. Biological age (b-Age) was estimated with Hannumm algorithm, based on DNA methylation in 71 CpGs. Results: The bivariate analyses for association with 3-mRS showed a significant results of NIHSS, c-Age, b-Age, p-mRS, and current smoking (all with p<0.001). Recanalization treatment showed no significant differences in bivariate analysis. In multivariate ordinal models, b-Age kept its significance (p=0.025) nullifying c-Age (p=0.84). Initial NIHSS, p-mRS and recanalization treatment kept also significant results (p<0.001). Conclusions: Biological Age, estimated by DNA methylation, is an independent predictor of stroke prognosis, irrespective to chronological age. "Healthy aging” affects the capacity of recovering after an ischemic stroke.

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Blood-based epigenetic estimators of chronological age in human adults using DNA methylation data from the Illumina MethylationEPIC array

BMC Genomics ◽

10.1186/s12864-020-07168-8 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Yunsung Lee ◽

Kristine L. Haftorn ◽

William R. P. Denault ◽

Haakon E. Nustad ◽

Christian M. Page ◽

...

Keyword(s):

Dna Methylation ◽

High Precision ◽

Pearson Correlation ◽

Gene Expression Omnibus ◽

Chronological Age ◽

Large Sample Size ◽

Training Set ◽

Age Related ◽

Illumina Humanmethylation450 Beadchip ◽

Human Adults

Abstract Background Epigenetic clocks have been recognized for their precise prediction of chronological age, age-related diseases, and all-cause mortality. Existing epigenetic clocks are based on CpGs from the Illumina HumanMethylation450 BeadChip (450 K) which has now been replaced by the latest platform, Illumina MethylationEPIC BeadChip (EPIC). Thus, it remains unclear to what extent EPIC contributes to increased precision and accuracy in the prediction of chronological age. Results We developed three blood-based epigenetic clocks for human adults using EPIC-based DNA methylation (DNAm) data from the Norwegian Mother, Father and Child Cohort Study (MoBa) and the Gene Expression Omnibus (GEO) public repository: 1) an Adult Blood-based EPIC Clock (ABEC) trained on DNAm data from MoBa (n = 1592, age-span: 19 to 59 years), 2) an extended ABEC (eABEC) trained on DNAm data from MoBa and GEO (n = 2227, age-span: 18 to 88 years), and 3) a common ABEC (cABEC) trained on the same training set as eABEC but restricted to CpGs common to 450 K and EPIC. Our clocks showed high precision (Pearson correlation between chronological and epigenetic age (r) > 0.94) in independent cohorts, including GSE111165 (n = 15), GSE115278 (n = 108), GSE132203 (n = 795), and the Epigenetics in Pregnancy (EPIPREG) study of the STORK Groruddalen Cohort (n = 470). This high precision is unlikely due to the use of EPIC, but rather due to the large sample size of the training set. Conclusions Our ABECs predicted adults’ chronological age precisely in independent cohorts. As EPIC is now the dominant platform for measuring DNAm, these clocks will be useful in further predictions of chronological age, age-related diseases, and mortality.

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Epigenetic Marker of Telomeric Age is Associated with Exacerbations and Hospitalizations in Chronic Obstructive Pulmonary Disease

10.21203/rs.3.rs-847329/v1 ◽

2021 ◽

Author(s):

Ana I Hernández Cordero ◽

Chen Xi Yang ◽

Xuan Li ◽

Stephen Milne ◽

Virginia Chen ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Dna Methylation ◽

Health Status ◽

Pulmonary Disease ◽

Cox Proportional Hazards Model ◽

Chronological Age ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Age Related ◽

Increased Risk

Abstract Background: Chronic obstructive pulmonary disease (COPD) is an age-related condition that has been associated with early telomere attrition; the clinical implications of telomere shortening in COPD are not well known. In this study we aimed to determine the relationship of the epigenetic regulation of telomeric length in peripheral blood with the risk of exacerbations and hospitalization in patients with COPD. Methods: Blood DNA methylation profiles were obtained from 292 patients with COPD enrolled in the placebo arm of the Macrolide Azithromycin to Prevent Rapid Worsening of Symptoms Associated With Chronic Obstructive Pulmonary Disease study (MACRO) and who were followed for 1-year. We calculated telomere length based on DNA methylation markers (DNAmTL) and related this biomarker to the risk of exacerbation and hospitalization and health status (St. George respiratory questionary score [SGRQ]) over this time using a Cox proportional hazards model. We also used linear models to investigate the associations of DNAmTL with the rates of exacerbations and hospitalizations (adjusted for chronological age, lung function, race, sex, smoking, and body mass index).Results: Participants with short DNAmTL demonstrated increased risk of exacerbation (P=0.02) and hospitalization (P=0.03) compared to those with longer DNAmTL. DNAmTL age acceleration was associated with higher rates of exacerbation (P=1.35x10-04) and hospitalization (P=5.21x10-03) and poor health status (SGRQ) independent of chronological age (P=0.03).Conclusion: Telomeric age based on blood DNA methylation is associated with COPD exacerbation and hospitalization and thus is a promising biomarker for poor outcomes in COPD.

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DNA methylation GrimAge and Incident Diabetes: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

10.2337/figshare.14336537.v1 ◽

2021 ◽

Author(s):

Kyeezu Kim ◽

Brian T. Joyce ◽

Yinan Zheng ◽

Pamela J. Schreiner ◽

David R. Jacobs Jr. ◽

...

Keyword(s):

Dna Methylation ◽

Young Adults ◽

Coronary Artery ◽

Normal Weight ◽

Incident Diabetes ◽

Chronological Age ◽

Age Related ◽

Epigenetic Age ◽

One Year

DNA methylation-based biological age (epigenetic age) has been suggested as a useful biomarker of age-related conditions including type 2 diabetes (T2D), and its newest iterations (GrimAge measurements) have shown early promise. In this study, we explored the association between epigenetic age and incident T2D, in the context of their relationships with obesity. <p>A total of 1,057 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study were included in the current analyses. We stratified the participants into three groups; normal weight, overweight, and obese. A one-year increase of GrimAge was associated with higher 10-year (Y15 to Y25) incidence of T2D (OR=1.06, 95% CI=1.01-1.11). GrimAge acceleration, which represents the deviation of GrimAge from chronological age, was derived from the residuals of a model of GrimAge and chronological age, and any GrimAge acceleration (Positive GrimAA; having GrimAge older than chronological age) was associated with significantly higher odds of 10-year incidence of T2D in obese participants (OR=2.57, 95% CI=1.61-4.11). Cumulative obesity was estimated by years since obesity onset, and GrimAge partially mediated the statistical association between cumulative obesity and incident diabetes or prediabetes (proportion mediated = 8.0%). </p> In conclusion, both <a>older and accelerated GrimAge were associated with higher risk of T2D, particularly among obese participants. GrimAge also statistically mediated the associations between cumulative obesity and T2D. </a>Our findings suggest that epigenetic age measurements with DNA methylation can potentially be utilized as a risk factor or biomarker associated with T2D development.

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DNA METHYLATION: CAUSE OR CONSEQUENCE OF AGING?

Innovation in Aging ◽

10.1093/geroni/igz038.127 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S32-S33

Author(s):

Morgan E Levine ◽

Sara Hagg

Keyword(s):

Dna Methylation ◽

Biological Age ◽

Causal Role ◽

Epigenetic Mark ◽

Epigenetic Changes ◽

Recent Advances ◽

Age Related

Abstract Epigenetic changes are one of the Hallmarks of Aging. DNA methylation is a key epigenetic mark that has been shown to change during aging. Several "clocks" have been developed whereby changes in DNA methylation can be used to predict chronological, and perhaps, biological age. This symposium will focus on recent advances in understanding how and why changes in DNA methylation occur during aging and whether these changes play a causal role in age-related functional declines and disease.

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The epigenetic tracks of aging

Biological Chemistry ◽

10.1515/hsz-2014-0180 ◽

2014 ◽

Vol 395 (11) ◽

pp. 1307-1314 ◽

Cited By ~ 39

Author(s):

Carola Ingrid Weidner ◽

Wolfgang Wagner

Keyword(s):

Dna Methylation ◽

Chromatin Structure ◽

Underlying Mechanism ◽

Histone Code ◽

Chronological Age ◽

Epigenetic Alterations ◽

Biological Functions ◽

Age Related ◽

Random Defects ◽

Dnam Level

Abstract Aging is associated with the deterioration of biological functions, which is either caused by accumulation of random defects or mediated by a controlled process. This article provides an overview of age-associated epigenetic alterations in the histone code, DNA-methylation (DNAm) pattern, and chromatin structure. In particular, age-related DNAm changes are highly reproducible at specific sites in the genome. The DNAm level at few CpGs facilitates estimation of chronological age and there is evidence that such predictions are indicative for biological age. Overall, aging appears to be associated with a tightly regulated epigenetic process, but the underlying mechanism remains to be elucidated.

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Epigenetic Changes in Response to Tai Chi Practice: A Pilot Investigation of DNA Methylation Marks

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/841810 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 16

Author(s):

Hua Ren ◽

Veronica Collins ◽

Sandy J. Clarke ◽

Jin-Song Han ◽

Paul Lam ◽

...

Keyword(s):

Dna Methylation ◽

Tai Chi ◽

Well Being ◽

Epigenetic Changes ◽

Biological Mechanisms ◽

Age Related ◽

Significant Difference ◽

Pilot Investigation ◽

Tai Chi Exercise ◽

Epigenetic Biomarker

Tai chi exercise has been shown to improve physiological and psychosocial functions, well-being, quality of life, and disease conditions. The biological mechanisms by which tai chi exerts its holistic effects remain unknown. We investigated whether tai chi practice results in positive epigenetic changes at the molecular level.Design. The DNA methylation profiles of sixty CpG-dinucleotide marks in female tai chi practitioners (N=237; 45–88 years old) who have been practising tai chi for three or more years were compared with those of age-matched control females (N=263) who have never practised tai chi.Results. Six CpG marks originating from three different chromosomes reveal a significant difference (P<0.05) between the two cohorts. Four marks show losses while two marks show gains in DNA methylation with age in the controls. In the tai chi cohort all six marks demonstrate significant slowing (by 5–70%) of the age-related methylation losses or gains observed in the controls, suggesting that tai chi practice may be associated with measurable beneficial epigenetic changes.Conclusions. The results implicate the potential use of DNA methylation as an epigenetic biomarker to better understand the biological mechanisms and the health and therapeutic efficacies of tai chi.

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Environmental enrichment preserves a young DNA methylation landscape in the aged mouse hippocampus

Nature Communications ◽

10.1038/s41467-021-23993-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Sara Zocher ◽

Rupert W. Overall ◽

Mathias Lesche ◽

Andreas Dahl ◽

Gerd Kempermann

Keyword(s):

Dna Methylation ◽

Brain Function ◽

Environmental Enrichment ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Aged Mouse ◽

Lifestyle Interventions ◽

Epigenetic Changes ◽

Aging Effects ◽

Age Related

AbstractThe decline of brain function during aging is associated with epigenetic changes, including DNA methylation. Lifestyle interventions can improve brain function during aging, but their influence on age-related epigenetic changes is unknown. Using genome-wide DNA methylation sequencing, we here show that experiencing a stimulus-rich environment counteracts age-related DNA methylation changes in the hippocampal dentate gyrus of mice. Specifically, environmental enrichment prevented the aging-induced CpG hypomethylation at target sites of the methyl-CpG-binding protein Mecp2, which is critical to neuronal function. The genes at which environmental enrichment counteracted aging effects have described roles in neuronal plasticity, neuronal cell communication and adult hippocampal neurogenesis and are dysregulated with age-related cognitive decline in the human brain. Our results highlight the stimulating effects of environmental enrichment on hippocampal plasticity at the level of DNA methylation and give molecular insights into the specific aspects of brain aging that can be counteracted by lifestyle interventions.

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Heat stress and immune response phenotype affect DNA methylation in blood mononuclear cells from Holstein dairy cows

Scientific Reports ◽

10.1038/s41598-021-89951-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

A. M. Livernois ◽

B. A. Mallard ◽

S. L. Cartwright ◽

A. Cánovas

Keyword(s):

Dna Methylation ◽

Immune Response ◽

Heat Stress ◽

Cellular Response ◽

Molecular Mechanisms ◽

Mononuclear Cells ◽

Heat Waves ◽

Promoter Regions ◽

Blood Mononuclear Cells

AbstractHeat stress negatively affects health and production in cows. Examining the cellular response to heat stress could reveal underlying protective molecular mechanisms associated with superior resilience and ultimately enable selection for more resilient cattle. This type of investigation is increasingly important as future predictions for the patterns of heat waves point to increases in frequency, severity, and duration. Cows identified as high immune responders based on High Immune Response technology (HIR) have lower disease occurrence compared to their average and low immune responder herd-mates. In this study, our goal was to identify epigenetic differences between high and low immune responder cows in response to heat stress. We examined genome-wide DNA methylation of blood mononuclear cells (BMCs) isolated from high and low cows, before and after in vitro heat stress. We identified differential methylation of promoter regions associated with a variety of biological processes including immune function, stress response, apoptosis, and cell signalling. The specific differentially methylated promoter regions differed between samples from high and low cows, and results revealed pathways associated with cellular protection during heat stress.

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