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

Aging improves pancreatic beta-cell function in mice. This is a surprising finding because aging is typically associated with functional decline. We performed single-cell RNA sequencing of beta-cells from 3-and 26-month-old mice to explorehowchanges in gene expression contribute to improved function with age. The old mice were healthy and had reduced blood glucose levels and increased beta-cell mass, which correlated to their body weight. beta-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 beta-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 beta-cell mass or functional beta-cell decline in mice.