Single-Cell RNAseq Reveals That Pancreatic β-Cells From Very Old Male Mice Have a Young Gene Signature

• Published in: Endocrinology (Philadelphia) Vol. 157; no. 9; pp. 3431 - 3438
• Main Authors: Xin, Yurong, Okamoto, Haruka, Kim, Jinrang, Ni, Min, Adler, Christina, Cavino, Katie, Na, Erqian, Murphy, Andrew J, Yancopoulos, George D, Lin, Calvin, Gromada, Jesper
• Format: Journal Article
• Language: English
• Published: United States Endocrine Society 01-09-2016; Oxford University Press
• Subjects: Aging; Aging - metabolism; Animals; Beta cells; Blood levels; Body weight; Cell cycle; Cell death; Cell migration; Cell survival; Cellular Senescence; Gene expression; Gene sequencing; Genes; Glucose - metabolism; Homeostasis; Insulin-Secreting Cells - metabolism; Male; Mice, Inbred C57BL; Pancreas; Sequence Analysis, RNA; Single-Cell Analysis; Transcription Factors - metabolism; Transcriptome; Transcriptomes
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2016-1235

Aging improves pancreatic β-cell function in mice. This is a surprising finding because aging is typically associated with functional decline. We performed single-cell RNA sequencing of β-cells from 3- and 26-month-old mice to explore how changes in gene expression contribute to improved function with age. The old mice were healthy and had reduced blood glucose levels and increased β-cell mass, which correlated to their body weight. β-Cells from young and old mice had similar transcriptome profiles. In fact, only 193 genes (0.89% of all detected genes) were significantly regulated (≥2-fold; false discovery rate < 0.01; normalized counts > 5). Of these, 183 were down-regulated and mainly associated with pathways regulating gene expression, cell cycle, cell death, and survival as well as cellular movement, function, and maintenance. Collectively our data show that β-cells from very old mice have transcriptome profiles similar to those of young mice. These data support previous findings that aging is not associated with reduced β-cell mass or functional β-cell decline in mice.