Abstract
SUMMARYAging 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.
Highlights
Aging is an inevitable physiological process in which molecular and cellular damage accumulate, leading to health decline and increased vulnerability to disease and death (Aunan et al, 2016; Melzer et al, 2020)
The majority of the genome is transcribed into non-coding transcripts, the main category of which is long non-coding RNAs, an emerging class of players in various biological processes (BPs) including aging (Cao et al, 2019; Grammatikakis et al, 2014; Kim et al, 2016; Kour and Rath, 2016; Xing et al, 2017)
We found that white adipose tissue (WAT) had the highest number of AR-Long non-coding RNAs (lncRNAs) and displayed the most dynamic AR-lncRNA$AR-mRNA crosstalk evolved during aging among all examined organs, strongly suggesting that adipose tissue is a leading contributor to the organismal decline
Summary
Zhou et al generated a comprehensive RNA-seq dataset of 11 tissues throughout the mouse lifespan, identified thousands of aging-regulated lncRNAs, and revealed leading transcriptome alterations in adipose tissue during aging. One of the AR-lncRNAs, lnc-AdipoAR1, regulates adipogenesis. This study serves as a valuable resource for further studies on lncRNAs during aging. Highlights d Gene expression of 11 tissues was profiled throughout the lifespan of mice d Aging-regulated lncRNAs exhibit more tissue specificity than other lncRNAs d Adipose tissue is a leading contributor to aging-related transcriptome alterations d An aging-regulated lncRNA, lnc-AdipoAR1, is essential for adipogenesis. May 26, 2020 a 2020 The Author(s).
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