Modeling pancreatic islet aging: mitochondrial dysfunction and functional rescue in 3D organoids by exogenous mitochondrial delivery.

This study models pancreatic islet aging using 3D organoids derived from senescent rPI-MSCs. This system is characterized by a functional bottleneck where, despite immunofluorescence and qPCR confirming robust insulin and PDX1 upregulation, senescent organoids lack mature glucose-sensing machinery via decreased glucokinase expression. Consequently, dithizone (DTZ) staining and ELISA confirm defective zinc-insulin complexation and depleted insulin secretion. This sensory block culminates in an abolished glucose-stimulated insulin secretion (GSIS) index. Remarkably, exogenous mitochondrial delivery overcomes this metabolic block, rescuing mitochondrial potential and partially mitigating the functional deficits associated with the senescent phenotype.