Genome-wide Profiling Identifies DNA Methylation Signatures of Aging in Rod Photoreceptors Associated with Alterations in Energy Metabolism
Genome-wide Profiling Identifies DNA Methylation Signatures of Aging in Rod Photoreceptors Associated with Alterations in Energy Metabolism
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DOI：
10.1016/j.celrep.2020.107525
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发表时间：
2020-04-21
期刊：
影响因子：
8.8
通讯作者：
Swaroop, Anand
中科院分区：
文献类型：
--
作者：
Corso-Diaz, Ximena;Gentry, James;Swaroop, Anand
与衰老相关的功能衰退伴随着表观基因组的改变。为了探索可能随年龄影响视觉功能的 DNA 修饰，我们对四个年龄段的纯化小鼠视杆光感受器进行全基因组亚硫酸氢盐测序，并鉴定了 2,054 个差异甲基化区域 (DMR)。我们在衰老早期阶段和视杆细胞调节区域检测到许多 DMR，其中一些聚集在染色体热点，特别是在 10 号染色体上，其中包括长寿相互作用组。甲基化组与年龄相关转录组变化、染色质特征和一级蛋白质-蛋白质相互作用的整合揭示了与杆功能、衰老和能量代谢相关的改变途径中 DMR 的富集。一致地，我们在离体测定中检测到随着视网膜年龄的增加，基础线粒体呼吸减少，脂肪酸依赖性增加。我们的研究揭示了年龄依赖性基因组和染色质特征易受视杆光感受器 DNA 甲基化变化的影响，并确定了衰老过程中 DNA 甲基化与能量代谢之间的联系。
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.