The pathological characters of islets aging in old rhesus monkeys

The loss of β cell mass and function in aged population plays a critical role in the prevalence of Type 2 diabetes. However, the causal relations between aging and age-related pancreatic islets degeneration still have not been fully elucidated. Rhesus monkey is one of the most ideal nonhuman primate animal models of a wide range of human diseases, including diabetes and aging-related diseases. In the present study, we observed the overall physiological function, glycolipid metabolism and islet function of middle-age and elderly rhesus monkeys, and compared their gene expression profiles by transcriptome sequencing of isolated islets. Through these analyses, we are aimed to evaluate the pathological characters of islets of old rhesus monkeys in the process of aging, and to provide some tips for the prevention and treatment of diabetes in the elderly population. The results suggested that there was no significant physiological disorder in monkeys of approximately 20 years old, except the glucose metabolism was mildly disturbed. In pancreas tissues and isolated islets of elderly monkeys, we found that the islets sizes were distinctly decreased, and the insulin secretion was compromised. Notably, the islets fibrosis and proportion of insulin/glucagon co-expressing cells increased significantly. Moreover, the β cell identity markers, transcription factors PDX1 and Nkx6.1 were losing with advancing age. Analysis of the RNA sequencing of isolated islets showed the genes related to type 1 diabetes and β cell function changed markedly. In conclusion, we found that in the elderly monkeys around 20 years old, the decreased islets size and compromised insulin secretion may contribute to the disturbed glucose metabolism, and the loss of β cell identity markers is a typical molecular change of islet senescence.