Searching for the β-Cell Fountain of Youth.

Aging affects every species and tissue but not in equal ways. Human pancreatic β-cells lose their ability to replicate, regenerate, and secrete insulin as one gets older. This natural process increases risk of developing diabetes as you age and is a concern for donor islets and stem cells obtained from older subjects destined for transplantation or emerging regenerative therapies. Using fluidic sorting and RNA sequencing on single cells, Xin et al describe a transcriptional signature of mouse β-cell aging between adulthood and a very old age. Amazingly, expression levels of more than 99% of genes do not change over time, despite the long lifespan of this specialized tissue. They identify a novel set of transcription factors that can explain decreases in cell survival and proliferation genes and potentially drive age-associated decline in regenerative capacity. Yet somehow, mouse β-cells maintain pathways regulating glucose metabolism and β-cell function despite experiencing challenges commonly associated with old age, including increased weight and fat mass. The authors conclude that β-cells of old mice are overall strikingly similar to young β-cells, implying that mechanisms may exist to resist aging and maintain their 'youth'. These new discoveries have interesting implications for efforts to preserve or improve function of human β-cells, providing potential clues toward prolonging the life and health of donor tissues or islets of people with diabetes.