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小鼠长非编码 RNA 全景揭示了衰老过程中脂肪组织中主要转录组的改变。

A Landscape of Murine Long Non-Coding RNAs Reveals the Leading Transcriptome Alterations in Adipose Tissue during Aging.

机构信息

Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.

Naomi Berrie Diabetes Center, Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

出版信息

Cell Rep. 2020 May 26;31(8):107694. doi: 10.1016/j.celrep.2020.107694.

DOI:10.1016/j.celrep.2020.107694
PMID:32460027
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7603645/
Abstract

Aging is an inevitable process that involves profound physiological changes. Long non-coding RNAs (lncRNAs) are emerging as important regulators in various biological processes but are not systemically studied in aging. To provide an organism-wide lncRNA landscape during aging, we conduct comprehensive RNA sequencing (RNA-seq) analyses across the mouse lifespan. Of the 1,675 aging-regulated lncRNAs (AR-lncRNAs) identified, the majority are connected to inflammation-related biological pathways. AR-lncRNAs exhibit high tissue specificity; conversely, those with higher tissue specificity are preferentially regulated during aging. White adipose tissue (WAT) displays the highest number of AR-lncRNAs and develops the most dynamic crosstalk between AR-lncRNA and AR-mRNA during aging. An adipose-enriched AR-lncRNA, lnc-adipoAR1, is negatively correlated with aging, and knocking it down inhibits adipogenesis, phenocopying the compromised adipogenic capacity of aged fat. Our works together reveal AR-lncRNAs as essential components in aging and suggest that although each tissue ages in a distinct manner, WAT is a leading contributor to aging-related health decline.

摘要

衰老是一个不可避免的过程，涉及到深刻的生理变化。长非编码 RNA（lncRNA）作为各种生物学过程中的重要调节因子而出现，但在衰老过程中并没有系统地研究。为了在衰老过程中提供一个全面的 lncRNA 图谱，我们对小鼠的整个生命周期进行了全面的 RNA 测序（RNA-seq）分析。在所鉴定的 1675 个与衰老相关的 lncRNA（AR-lncRNA）中，大多数与炎症相关的生物学途径有关。AR-lncRNA 具有高度的组织特异性；相反，那些具有更高组织特异性的 lncRNA 在衰老过程中优先被调控。白色脂肪组织（WAT）显示出最多的 AR-lncRNA，并在衰老过程中显示出 AR-lncRNA 和 AR-mRNA 之间最具动态的串扰。一个脂肪组织丰富的 AR-lncRNA，lnc-adipoAR1，与衰老呈负相关，敲低它会抑制脂肪生成，表现出老年脂肪的脂肪生成能力受损。我们的研究共同揭示了 AR-lncRNA 作为衰老过程中的重要组成部分，并表明尽管每个组织以不同的方式衰老，但 WAT 是导致与衰老相关的健康衰退的主要因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f800/7603645/2c7a832fb984/nihms-1639069-f0006.jpg
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