Specific senescence detection in pancreatic islets

摘要 随着老龄化人口的迅速增长，与年龄相关的疾病对健康的威胁越来越大。 其中一个例子是2型糖尿病(T2D)，这是一种以高血糖水平为特征的慢性疾病 由于胰岛素分泌受损和胰岛素抵抗。大约9%的美国人患有糖尿病， 它的患病率随着年龄的增长而增加；65岁或65岁以上的美国人的发病率增加了两倍。 衰老是一个缺乏细胞分裂和组织更新的过程，是衰老和衰老的重要因素。 相关疾病。越来越多的证据已经确立了细胞衰老和糖尿病之间的联系。 胰腺β细胞衰老被认为是T2D的一个贡献者，提示其机制是通过 哪种衰老与糖尿病有关，因为β细胞功能和质量的下降是T2D的标志 进步。然而，T2D进展过程中衰老的发展和动力学尚不清楚， 而对可用的衰老靶向治疗的评估仅限于组织水平，主要是由于 缺乏灵敏的工具来识别胰岛中的衰老细胞，特别是在体内。在这项研究中，我们 提议开发一种用于实时检测胰岛衰老的分子探针，我们将 在分离的胰岛和T2D小鼠体内模型中对该探针进行评估。该项目的完成将 研制了一种用于实时检测胰岛衰老的新型分子探针。这将是一场 糖尿病衰老研究的不可缺少的工具，并用于验证 衰老作为防治T2D的治疗靶点。相同的探头设计策略 也可以用来开发其他与年龄相关的疾病的探针。

Abstract With the rapidly growing aging population, age-related diseases have become an increasing threat to health. One such example is type 2 diabetes (T2D), a chronic condition characterized by high blood glucose levels due to impaired insulin secretion and insulin resistance. Around 9% of the American population has diabetes, the prevalence of which increases with age; the incidence rate triples in Americans aged 65 or older. Senescence, a process lacking cell division and tissue renewal, is an essential contributor to aging and age- related diseases. Mounting evidence has established links between cellular senescence and diabetes. Pancreatic β cell senescence has been implicated as a contributor to T2D, suggesting a mechanism through which senescence contributes to diabetes, as the decline of β cell function and mass is a hallmark of T2D progression. However, the development and kinetics of senescence during the progression of T2D is unknown, and the evaluation of available senescence-targeting therapies is limited to the tissue level, primarily due to the lack of sensitive tools for identifying senescent cells in pancreatic islets, particularly in vivo. In this study, we propose to develop a molecular probe for the real-time detection of senescence in pancreatic islets, and we will evaluate the probe in isolated pancreatic islets and in T2D mice models in vivo. Completion of the project will generate a novel molecular probe for the real-time detection of senescence in pancreatic islets. It will be an indispensable tool for the study of senescence in diabetes, and for the validation of the plausibility of senescence as a therapeutic target for the prevention and treatment of T2D. The same probe design strategy can also be used to develop probes for other age-related diseases.