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

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. [Display omitted] •Gene expression of 11 tissues was profiled throughout the lifespan of mice•Aging-regulated lncRNAs exhibit more tissue specificity than other lncRNAs•Adipose tissue is a leading contributor to aging-related transcriptome alterations•An aging-regulated lncRNA, lnc-AdipoAR1, is essential for adipogenesis 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.