Modulation of gap junctions in senescent endothelial cells.

Gap junction-mediated intercellular communication (GJIC) was decreased in senescent human umbilical vein endothelial cells (HUVEC), as detected by Gap-Frap studies. The molecular basis of this reduction and the effects of the calcium ionophore A23187 and epidermal growth factor (EGF) on young and old HUVEC have been investigated. Northern and Western analyses reveal that the levels of both cx43 (connexin 43) messenger RNA and protein decline as HUVEC age in vitro. While both young and senescent cells responded immediately to increases in intracellular calcium concentrations, only young cells produced a dose-dependent decrease in cell coupling in response to the addition of exogenous EGF. The down-regulation of cx43 mRNA and protein levels in senescent endothelial cells suggests that GJIC might play a role in the aging process. The inability of senescent cells to down-regulate gap junctions in response to EGF reflects a defect in the regulatory mechanism of gap junction activity in senescent cells.