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

Aging improves pancreatic β-cell function in mice. This is a surprising finding since 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, 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 downregulated 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.