Specific senescence detection in pancreatic islets

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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.