On the aging of organisms and their cells.

An explanation of organismic ageing based on a limited division capacity of dividing cells is difficult to reconcile with much of the available data. The physiology of cells in ageing organisms tends, on the contrary, to suggest that organisms age as a result of degeneration in their non-dividing cell populations. Senescence in these non-mitotic cells resmebles the ageing of the non-dividing fraction of cell cultures clonally senescing, or maintained in long-term quiescence in vitro. As cultures of diploid human fibroblasts senesce there is an accumulation of non-dividing cells. Alterations in these post-mitotic cells can explain the senescent properties of late passage cultures. It is proposed that during the in vitro senescence of fibroblast cultures, cell ageing results from, as opposed to causes, the absence of mitosis. Cell ageing may primarily result from changes in the chromatin induced by the non-mitotic state.