Genome-wide Profiling Identifies DNA Methylation Signatures of Aging in Rod Photoreceptors Associated with Alterations in Energy Metabolism.
DNA methylome
beta oxidation
differential methylation clusters
epigenome
gene regulation
mitochondria
retinal aging
rod photoreceptor
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
21 04 2020
21 04 2020
Historique:
received:
18
09
2019
revised:
11
02
2020
accepted:
26
03
2020
entrez:
23
4
2020
pubmed:
23
4
2020
medline:
15
5
2021
Statut:
ppublish
Résumé
Aging-associated functional decline is accompanied by alterations in the epigenome. To explore DNA modifications that could influence visual function with age, we perform whole-genome bisulfite sequencing of purified mouse rod photoreceptors at four ages and identify 2,054 differentially methylated regions (DMRs). We detect many DMRs during early stages of aging and in rod regulatory regions, and some of these cluster at chromosomal hotspots, especially on chromosome 10, which includes a longevity interactome. Integration of methylome to age-related transcriptome changes, chromatin signatures, and first-order protein-protein interactions uncover an enrichment of DMRs in altered pathways that are associated with rod function, aging, and energy metabolism. In concordance, we detect reduced basal mitochondrial respiration and increased fatty acid dependency with retinal age in ex vivo assays. Our study reveals age-dependent genomic and chromatin features susceptible to DNA methylation changes in rod photoreceptors and identifies a link between DNA methylation and energy metabolism in aging.
Identifiants
pubmed: 32320661
pii: S2211-1247(20)30425-3
doi: 10.1016/j.celrep.2020.107525
pmc: PMC7228806
mid: NIHMS1586764
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
107525Subventions
Organisme : Intramural NIH HHS
ID : ZIA EY000450
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA EY000546
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA EY000456
Pays : United States
Informations de copyright
Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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