Chromatin reorganization during senescence of proliferating cells

It was previously proposed (Macieira-Coelho, 1979) that aging of proliferating cells is the result of genome reorganization taking place during the division cycle. This hypothesis was investigated and a reorganization could indeed be ascertained in the different hierarchical orders of DNA structure; a correlation was found between changes in chromatin organization and the impairment of cell cycle-related events. Indeed, like the latter, the reorganization of chromatin structure is characterized by a succession of subtle changes through the cell population life span, and a final short stage with abrupt events. The final events seem to concern mainly the organization of heterochromatin. The reorganization in the genome is accompanied by structural changes in the cellular scaffold and an evolution of cell morphology. The remodeling occurring in the cell through serial divisions seems to take place in such a way as to decrease the probability of further reorganizations, tending to a limit. The decline of the proliferative activity seems to be the result of the tendency to reach this limit.