DNA Methylation Clocks in Aging: Categories, Causes, and Consequences

Field, Adam E.; Robertson, Neil; Wang, Tina; Havas, Aaron; Ideker, Trey; Adams, Peter D.

doi:10.1016/j.molcel.2018.08.008

Cited by 474 publications

(447 citation statements)

References 150 publications

(304 reference statements)

Supporting

Mentioning

390

Contrasting

Unclassified

Order By: Relevance

“…Changes in nutritional and epigenetic state are integral to aging. This can be judged by the central role of the mTOR pathway [ 9,10 ] and histone/DNA methylation [ 58,59 ] in organismal aging. αKG has emerged as master regulatory metabolite in aging biology as it is a key TCA intermediate, a cofactor for numerous transamination reactions, [ 60,61 ] a cofactor for the prolyl hydroxylase dependent hydroxylation of the transcription factor hypoxia inducible factor‐1 (HIF‐1) [ 62–64 ] and a cofactor for epigenetic enzymes, histone, and DNA demethylases.…”

Section: Application Of Metabolomics For Biomarker Discovery In Agingmentioning

confidence: 99%

The Aging Metabolome—Biomarkers to Hub Metabolites

Sharma

Ramanathan

2020

Proteomics

View full text Add to dashboard Cite

Aging biology is intimately associated with dysregulated metabolism, which is one of the hallmarks of aging. Aging‐related pathways such as mTOR and AMPK, which are major targets of anti‐aging interventions including rapamcyin, metformin, and exercise, either directly regulate or intersect with metabolic pathways. In this review, numerous candidate bio‐markers of aging that have emerged using metabolomics are outlined. Metabolomics studies also reveal that not all metabolites are created equally. A set of core “hub” metabolites are emerging as central mediators of aging. The hub metabolites reviewed here are nicotinamide adenine dinucleotide, reduced nicotinamide dinucleotide phosphate, α‐ketoglutarate, and β‐hydroxybutyrate. These “hub” metabolites have signaling and epigenetic roles along with their canonical roles as co‐factors or intermediates of carbon metabolism. Together these hub metabolites suggest a central role of the TCA cycle in signaling and metabolic dysregulation associated with aging.

show abstract

Section: Application Of Metabolomics For Biomarker Discovery In Agingmentioning

confidence: 99%

The Aging Metabolome—Biomarkers to Hub Metabolites

Sharma

Ramanathan

2020

Proteomics

View full text Add to dashboard Cite

show abstract

“…18 Furthermore, neonatal infection in mice led to heightened susceptibility to amyloid beta-induced neuroinflammation at adulthood with increased microglial activation and higher memory impairment in the novel object recognition test. [82][83][84] During normal aging, GO analysis of peripheral blood samples from pediatric and aged population revealed that methylation changes were highly related to developmental and inflammatory pathways. [74][75][76][77][78] Several world leaders in neonatal neurobiology, actively studying the inflammation-induced sensitization paradigm, are expressing grave concern over the increased risk of neurodegeneration following subsequent insults.…”

Section: F I G U R E 4 Methylation Levels Of Genes Of Interest Associmentioning

confidence: 99%

Alteration of the brain methylation landscape following postnatal inflammatory injury in rat pups

et al. 2019

View full text Add to dashboard Cite

This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. contributed equally to this study.Abbreviations: ASD, autism spectrum disorder; CpG, cytosine followed by guanine; DMR, differentially methylated region; DOHaD, developmental origins of health and disease; E. coli, Escherichia coli; GO, gene ontology; LPS, lipopolysaccharide; P3, postnatal day 3; P4, postnatal day 4; P24, postnatal day 24; PBS, phosphate-buffered saline; PFA, paraformaldehyde; RRBS, reduced representation bisulfite sequencing; WMI, white matter injury. AbstractPreterm infants are vulnerable to inflammation-induced white matter injury (WMI), which is associated with neurocognitive impairment and increased risk of neuropsychiatric diseases in adulthood. Epigenetic mechanisms, particularly DNA methylation, play a role in normal development and modulate the response to pathological challenges. Our aims were to determine how WMI triggered DNA methylation alterations in brains of neonatal rats and if such changes persisted over time. We used a robust model of WMI by injecting lipopolysaccharide (LPS) or sterile saline in the corpus callosum of 3-day-old (P3) rat pups. Brains were collected 24 hours (P4) and 21 days post-injection (P24). We extracted genomic DNA from the brain to establish genome-wide quantitative DNA methylation profiles using reduced representation bisulfite sequencing. Neonatal LPS exposure induced a persistent increased methylation of genes related to nervous system development and a reduced methylation of genes associated with inflammatory pathways. These findings suggest that early-life neuroinflammatory exposure impacts the cerebral methylation landscape with determining widespread epigenetic modifications especially in genes related to neurodevelopment. K E Y W O R D SDNA methylation, epigenetics, lipopolysaccharide, periventricular leukomalacia

show abstract

“…During aging, DNA methylation (DNAm) is continuously lost or gained at specific CG nucleotides (CpG sites) of our genome. Conversely, the DNAm levels at multiple CpG sites can be combined to estimate age, and these models are often referred to as "epigenetic clocks" (Field et al 2018).…”

Section: Introductionmentioning

confidence: 99%

New Targeted Approaches for Epigenetic Age Predictions

Han

Franzen

Stiehl

et al. 2019

Preprint

View full text Add to dashboard Cite

Aging causes epigenetic modifications, which are utilized as a biomarker for the aging process.While genome-wide DNA methylation profiles enable robust age-predictors by integration of many age-associated CG dinucleotides (CpGs), there are various alternative approaches for targeted measurements at specific CpGs that better support standardized and cost-effective highthroughput analysis. In this study, we utilized 4,650 Illumina BeadChip datasets of blood to select the best suited CpG sites for targeted analysis. DNA methylation analysis at these sites with either pyrosequencing or droplet digital PCR (ddPCR) revealed a high correlation with chronological age.In comparison, bisulfite barcoded amplicon sequencing (BBA-seq) gave slightly lower precision at individual CpGs. However, BBA-seq data revealed that the correlation of methylation levels with age at neighboring CpG sites follows a bell-shaped curve, often accompanied by a CTCF binding site at the peak. We demonstrate that within individual BBA-seq reads the DNA methylation at neighboring CpGs is not coherently modified but reveals a stochastic pattern. Based on this, we have developed an alternative model for epigenetic age predictions based on the binary sequel of methylated and non-methylated sites in individual reads, which reflects heterogeneity in epigenetic aging within a sample. Thus, the stochastic evolution of age-associated DNA methylation patterns, which seems to resemble epigenetic drift, enables epigenetic clocks for individual DNA strands.

show abstract

DNA Methylation Clocks in Aging: Categories, Causes, and Consequences

Cited by 474 publications

References 150 publications

The Aging Metabolome—Biomarkers to Hub Metabolites

The Aging Metabolome—Biomarkers to Hub Metabolites

Alteration of the brain methylation landscape following postnatal inflammatory injury in rat pups

New Targeted Approaches for Epigenetic Age Predictions

Contact Info

Product

Resources

About