Aging is the major risk factor for chronic disease development. Cellular senescence is a key mechanism that triggers or contributes to age-related phenotypes and pathologies. The endothelium, a single layer of cells lining the inner surface of a blood vessel, is a critical interface between blood and all tissues. Many studies report a link between endothelial cell senescence, inflammation, and diabetic vascular diseases. Here we identify, using combined advanced AI and machine learning, the Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1B (DYRK1B) protein as a possible senolytic target for senescent endothelial cells. We demonstrate that upon induction of senescence in vitro DYRK1B expression is increased in endothelial cells and localized at adherens junctions where it impairs their proper organization and functions. DYRK1B knock-down or inhibition restores endothelial barrier properties and collective behavior. DYRK1B is therefore a possible target to counteract diabetes-associated vascular diseases linked to endothelial cell senescence.

衰老是慢性病发展的主要危险因素。细胞衰老是触发或促成与年龄相关的表型和病理的关键机制。内皮是血管内表面的单层细胞，是血液和所有组织之间的关键界面。许多研究报告了内皮细胞衰老、炎症和糖尿病血管疾病之间的联系。在这里，我们结合先进的人工智能和机器学习，确定了双特异性酪氨酸磷酸化调节激酶 1B (DYRK1B) 蛋白作为衰老内皮细胞的可能的衰老目标。我们证明，在内皮细胞中诱导衰老后，DYRK1B 表达增加，并定位于粘附连接处，从而损害其正常组织和功能。DYRK1B敲低或抑制可恢复内皮屏障特性和集体行为。因此，DYRK1B 是对抗与内皮细胞衰老相关的糖尿病相关血管疾病的可能靶点。