Differential regulation of apoptotic cell death in senescent human cells

Aging of human cells can be reproduced in monolayer cultures, revealing the phenotype of replicative senescence. It was shown that diploid human fibroblasts enter a stable growth arrest phenotype at the end of their lifespan and, in particular, these cells are resistant to various apoptotic stimuli. In contrast, human endothelial cells from the umbilical vein (HUVEC) acquire a proapoptotic phenotype when reaching senescence and this probably results from reactive oxygen species (ROS) induced damage and associated signaling. Ceramides were shown to accumulate in senescent fibroblasts and are also known as potent regulators of apoptotic cell death. To further study age-associated changes in proneness to apoptosis between fibroblasts and endothelial cells, both cell types were challenged by administration of exogenous ceramide and apoptotic cell death was determined. While ceramide can efficiently induce apoptosis in both young and senescent cells of either histotype, quantitative evaluation of the data show that senescent fibroblasts are more resistant to apoptosis induction when compared to their young counterparts, whereas in the case of endothelial cells proneness for apoptosis is increased in senescent cells. Together, these data suggest significant differences in the regulation of apoptosis associated with senescence in fibroblasts and endothelial cells. © 2004 Elsevier Inc. All rights reserved.