It is revealed that protein steady state imbalance is a key characteristic and molecular driving force of islet beta cell aging.

In the past 30 years, with the aging of the population, the incidence of diabetes in China has increased rapidly.
at present, the total number of diabetes patients in the country has exceeded 100 million, and nearly 500 million adults are in prediabetes (damaged sugar tolerance), which has posed a serious challenge to the prevention and treatment of chronic diseases related to aging in China.
with the aging of islet cell function degeneration will cause the body can not respond to normal changes in blood sugar, thus the regulation of blood sugar (i.e. sugar tolerance) decreased, causing sugar metabolism disorders, and eventually developed into diabetes, and accompanied by blood vessels, retina, kidneys, nervous system and a series of tissue organs metabolic abnormalities.
therefore, the identification of islet cells in the aging susceptibility of the cell type, reveal the islet aging process of cell molecular degenerative changes, to explore the intervention of the decline of sugar tolerance of the key targets, istoe aging, accurate prevention and treatment of diabetes is very important.
However, the composition of islet cells is highly heterogeneous, containing a variety of cell types that secrete different kinds of hormones, in addition, due to ethical and sample acquisition of the technical difficulty, age sex strictly matched high-quality human islet samples difficult to obtain, these factors greatly restrict the mechanism of islet cell aging exploration. on June 10,
, qu Jing Research Group of the Institute of Zoology of the Chinese Academy of Sciences, Liu Guanghui Research Group, Tang Fuyu Research Group of Peking University, and Zhang Weihui Research Group of the Beijing Genomics Research Institute of the Chinese Academy of Sciences published an online research paper on A-cellomic siatlas of the case of the group.
the study system mapped a high-precision single-cell transcription map of non-human primate islet aging, revealing that protein steady state imbalance is a key characteristic and molecular driving force of islet beta cell aging.
researchers used high-precision single-cell transcription sequencing techniques to characterize the gene expression of a variety of ether cells, including alpha cells, beta cells, gamma cells and PP cells, and identified a new series of molecular markers.
through aging transcription noise analysis, aging marker analysis, and joint analysis with databases such as aging/diabetes, alpha and beta cells are more prone to abnormal changes in the aging process than other cell types.
the multi-angle analysis of the functional enrichment of differentially expressed genes, gene transcription control networks, and cell-to-cell interactions, the molecular spectrum changes associated with aging of alpha cells and beta cells were systematically analyzed.
noteworthy, the researchers found that aging causes significant damage to protein steady state in beta cells, as evidenced by abnormal accumulation of protein aggregates in older individual beta cells, and abnormal lying of ATF6 and IRE1 signaling pathway components in the unfolded protein response pathway (unfold protein response pathway, UPR), especially the intrabox molecular partner protein HSP90B1 in older individualbeta cells. Further studies
show that the overexpression of HSP90B1 in beta cells can lead to a decrease in insulin secretion under high glucose stimulation, suggesting that the increase in the expression of hSP90B1 in beta cells may be the driving force behind the reduced sugar tolerance in the elderly.
the study has reported for the first time in the world a single-cell transcription group map of non-human primate islet aging, which not only systematically analyzes the molecular characteristics of aging molecules of various cell types in the primate islet, but also reveals that protein steady state imbalance is the driving factor of islet beta cell aging, provides potential intervention targets for delaying islet aging and restoring the sugar tolerance of older individuals, and providing a whole new idea for effective prevention and treatment of diabetes.
the study was carried out in collaboration with the Institute of Zoology of the Chinese Academy of Sciences, Peking University, the Beijing Genomics Institute of the Chinese Academy of Sciences, the Institute of Biophysics of the Chinese Academy of Sciences, the Xuanwu Hospital of Capital Medical University, the Salk Institute of the United States, and the Beijing Hospital. Li Jingyi, associate researcher of the
Animal Institute, Zheng Yuxuan, ph.d, Peking University, Yan Pengze, researcher Song Mozhi and associate researcher Wang Si were the first authors.
Qu Jing, Tang Fuhui, Liu Guanghui and Zhang Weixuan are co-authors.
the research was guided and supported by Zhou Qi, a member of the Chinese Academy of Sciences, Chen Wei, a professor at Xuanwu Hospital, and Sun Liang, a professor at 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.
Source: Animal Research Institute.