A Landscape of Murine Long Non-Coding RNAs Reveals the Leading Transcriptome Alterations in Adipose Tissue during Aging
Qiuzhong Zhou,
Qianfen Wan,
Yuxi Jiang,
Jin Liu,
Li Qiang,
Lei Sun
Affiliations
Qiuzhong Zhou
Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore
Qianfen Wan
Naomi Berrie Diabetes Center, Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
Yuxi Jiang
Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore; Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, Zhejiang 325035, China; School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
Jin Liu
Centre for Quantitative Medicine, Health Services & Systems Research, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore
Li Qiang
Naomi Berrie Diabetes Center, Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Corresponding author
Lei Sun
Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore; Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore; Corresponding author
Summary: 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.
