Replicative senescence: considerations relating to the stability of heterochromatin domains.

Replicative senescence of human diploid fibroblasts (HDF) cultured in vitro is characterized by a progressive and irreversible loss of responsiveness to mitogenic stimulation by serum. While some constraints have been placed on the nature of HDF senescence, its underlying molecular mechanism(s) remain obscure. Here, the possibility is considered that defects in cell cycle-coupled reassembly of repressive chromatin domains may contribute to HDF senescence. Features of this model are discussed in relation to established models of HDF senescence based on telomere shortening and loss of DNA methylation.