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The proliferation, migration, and death of vascular endothelial and smooth muscle cells are crucial to the development of atherosclerosis and its related processes such as postangioplasty restenosis. While a great deal of attention has been paid to many of the factors that influence these events, relatively little attention has been given to one potentially important factor, the age of the cells concerned. Cell age is more appropriately measured in terms of the number of divisions since the cell differentiated from the germ line than in terms of chronological age. Following the work of Hayflick in the 1960s it has been known that virtually all somatic cells in culture go through a finite number of cell divisions and then enter a phase of senescence in which they are no longer susceptible to ordinary mitotic stimuli, and indeed where such stimuli can provoke cell death.1 ,2 This M1 phase is now thought to be controlled by specific tumour suppressor genes such as p53 and Rb.3-5 Cells can be “rescued” from M1 in a variety of ways and in particular by infection with certain transforming viruses—for example, SV40, which work by counteracting the effects of the tumour suppressor genes. Rescued cells go through further cycles of division but nearly all of them will eventually enter a second and lethal phase of senescence called M2. A tiny proportion survive and become immortal in that they continue to proliferate without further signs of senescence in a way indistinguishable from tumour cells.
It is now known, or at least strongly suspected, that the biological clock that determines the effective age of a cell resides in the telomeres. These are the extreme ends of chromosomal DNA, made up of a large number of repeats of a stereotyped and highly conserved nucleotide sequence, TTAGGG. Initial …