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

Aging improves pancreatic ß-cell function in mice. This is a surprising finding since aging is typically associated with functional decline. We performed single-cell RNA sequencing of ß-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 ß-cell mass, which correlated to their body weight. ß-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 ß-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 ß-cell mass or functional ß-cell decline in mice. Overall design: Single-cell RNA sequencing of mouse pancreatic islet beta cells

衰老可改善小鼠胰腺胰岛β细胞（β-cell）功能。这一发现颇为出人意料，因为衰老通常与功能衰退相关联。我们对3月龄与26月龄小鼠的胰岛β细胞开展了单细胞RNA测序（single-cell RNA sequencing），旨在探究基因表达变化如何随衰老进程助力功能提升。
实验所用的老年小鼠健康状态良好，其血糖水平降低、β细胞质量升高，且这一表型与其体重相关。年轻与老年小鼠的β细胞具有相似的转录组特征。事实上，仅193个基因（占所有检测到基因的0.89%）呈现出显著差异表达（变化倍数≥2倍；错误发现率（false discovery rate）<0.01；标准化计数>5）。其中183个基因表达下调，且主要富集于调控基因表达、细胞周期、细胞死亡与存活、细胞迁移以及细胞功能与稳态维持的通路中。
综上，我们的数据表明，高龄小鼠的β细胞转录组特征与年轻小鼠相似。这些数据佐证了此前的研究结论：在小鼠中，衰老并不会导致β细胞质量降低或β细胞功能衰退。
实验整体设计：对小鼠胰岛β细胞开展单细胞RNA测序。