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Scientists reveal the molecular mechanism of primate islet aging
[ Instrument R&D in Instrument Network ] In the past 30 years, with the aging of the population, the incidence of diabetes in China has risen sharply. At present, the total number of diabetic patients in the country has exceeded 100 million, and nearly 500 million adults are in pre-diabetes (impaired glucose tolerance), which has posed a serious challenge to the prevention and treatment of aging-related chronic diseases in my country. With the aging of islet cell function, the body will not respond normally to changes in blood glucose, and the ability to regulate blood glucose (ie, glucose tolerance) will decline, leading to disorders of glucose metabolism, eventually leading to diabetes, accompanied by blood vessels, retina, kidney, and nervous system. Wait for a series of tissue and organ metabolism abnormalities. Therefore, identifying the types of cells that are susceptible to aging in pancreatic islet cells, revealing the degenerative changes of cellular molecules during the process of pancreatic islet aging, and discovering the key targets for intervening in the decline of glucose tolerance are essential for delaying pancreatic islet aging and accurately preventing and treating diabetes. However, the composition of islet cells is highly heterogeneous and contains a variety of cell types that secrete different types of hormones; in addition, due to ethical and technical difficulties in sample acquisition, it is difficult to obtain high-quality human islet samples that are strictly matched in age and sex. These Factors greatly restrict the mechanism of primate islet cell aging.
On June 10th, Qu Jing Research Group, Liu Guanghui Research Group, Peking University Tang Fuchen Research Group of the Institute of Zoology, Chinese Academy of Sciences and Zhang Weiqi Research Group of the Beijing Institute of Genomics, Chinese Academy of Sciences published an article titled A single-cell online in National Science Review Research paper on transcriptomic atlas of primate pancreatic islet aging. This research system draws a high-precision single-cell transcription map of non-human primate islet senescence, revealing that protein homeostasis is the key feature and molecular driving force of islet β-cell aging.
The researchers used high-precision single-cell transcriptome sequencing technology to characterize the gene expression characteristics of various islet cells such as α cells, β cells, δ cells, and PP cells, and identified a series of novel molecular markers. Through analysis of aging transcription noise, analysis of aging markers, and joint analysis with databases such as aging/diabetes, it was found that α cells and β cells are more likely to undergo abnormal changes during aging than other cell types. Through multi-angle analysis of functional enrichment of differentially expressed genes, gene transcription regulatory network, and cell-to-cell interactions, we systematically analyze changes in the molecular spectrum of senescence-related alpha and beta cells. It is worth noting that the researchers found that aging causes severe damage to the protein homeostasis in β cells, which is specifically manifested in the abnormal accumulation of protein aggregates in β cells of elderly individuals and the unfolded protein response pathway (UPR) ) ATF6 and IRE1 signaling pathway components are abnormally up-regulated, especially the endoplasmic reticulum molecular chaperone protein HSP90B1 is up-regulated in β cells of elderly individuals. Further studies have shown that overexpression of HSP90B1 in β cells can lead to decreased insulin secretion under the stimulation of high concentration glucose, indicating that the up-regulated expression of HSP90B1 in β cells may be the driving force for impaired glucose tolerance in the elderly.
This study is the first in the world to report the single-cell transcriptome of non-human primate islet aging. Not only does it systematically analyze the molecular characteristics of senescence in multiple cell types in primate islets, but it also reveals that the protein homeostasis imbalance is the islet The driving factors of β-cell aging provide potential intervention targets for delaying islet aging and restoring the glucose tolerance of elderly individuals, and provide new ideas for the effective prevention and treatment of diabetes.
The research was carried out in collaboration with the Institute of Zoology, Chinese Academy of Sciences, Peking University, Beijing Institute of Genomics, Chinese Academy of Sciences Institute of Biophysics, Xuanwu Hospital of Capital Medical University, Salk Institute, Beijing Hospital and other institutions. Associate Researcher Li Jingyi of the Institute of Zoology, Zheng Yuxuan, Ph.D. student of Peking University, Yan Pengze, PhD student of the Institute of Zoology, Researcher Song Mozhi, and Associate Researcher Wang Si are the first authors. Qu Jing, Tang Fuchen, Liu Guanghui and Zhang Weiqi are co-corresponding authors. The research was directed and supported by Academician Zhou Qi of the Chinese Academy of Sciences, Professor Chen Biao of Xuanwu Hospital and Professor Sun Liang of Beijing Hospital, and was supported by the Ministry of Science and Technology, the National Natural Science Foundation of China, the Chinese Academy of Sciences and Beijing.