Replicative senescence of human endothelial cells in vitro involves G1 arrest, polyploidization and senescence-associated apoptosis

Human ageing is characterized by a progressive loss of physiological functi ons, increased tissue damage and defects in various tissue renewal systems. Age-related decreases of the cellular replicative. capacity can be reprodu ced by in vitro assays of cellular ageing. When diploid human fibroblasts r each their finite lifespan, they enter an irreversible G1 growth arrest sta tus referred to as replicative senescence. While deregulation of programmed cell death (apoptosis) is a key feature of age-related pathology in severa l tissues, this is not reflected in the standard in vitro senescence model of human fibroblasts, and the role of apoptosis during cellular ageing rema ins unclear. We have analyzed replicative senescence of human umbilical vei n endothelial cells (HUVEC) in vitro and found that senescent HUVEC also ar rest in the G1 phase of the cell cycle but, unlike fibroblasts, accumulate with a 4N DNA content, indicative of polyploidization. In contrast to human fibroblasts, senescent endothelial cells display a considerable increase i n spontaneous apoptosis. The data imply that age-dependent apoptosis is a r egular feature of human endothelial cells and suggest cell type specific di fferences in human ageing. (C) 2001 Elsevier Science Inc. All rights reserv ed.