Most of the reports on aging-induced Ca²⁺ signal modifications have been performed in excitable tissues. We have investigated the effects of aging in the spatiotemporal kinetics of calcium signals in pancreatic acinar cells isolated from adult and senescent mice. Cells were loaded with fura-2 and studied by digital microscopic imaging, and amylase secretion was assayed by a colorimetric method. In senescent cells, both the amplitude and the rate of [Ca²⁺]i rise in response to ACh was decreased compared to adult cells. The propagation of [Ca²⁺]i waves from the luminal to the basolateral pole of the cell, a characteristic feature of this cell type, was also inhibited in senescent cells. Although the amplitude of [Ca²⁺]i in response to cholecystokinin (CCK) was slightly inhibited in aged cells, the speed of rise and the spatial propagation of the signal were accelerated. The recruitment of [Ca²⁺]i oscillations induced by postprandial levels of CCK was inhibited in senescent cells, which displayed a de-regulated and slowly rising response. In addition, the rate of Ca²⁺ decay, the size of intracellular Ca²⁺ pools and the capacitative calcium entry were decreased by aging. These signalling changes were correlated with a decrease in the secretory response to ACh and CCK. Aged cells were also more sensitive to interferences in the NAADP pathway. In conclusion, aging of pancreatic cells impairs exocrine function and Ca²⁺ signals and modifies novel calcium signal pathways.

Supported by SCCSS0620 and BFU 2004-0687