Cellular Versus Organismal Aging

There has been much written about cellular senescence and the events that lead up to cell death (reviewed in reference 17). After a finite number of divisions, normal somatic cells invariably enter a state of

irreversibly arrested growth, a process termed replicative senescence . In fact, it has been proposed that escape from the regulators of senescence is the antecedent of malignant transformation. However, the role of replicative senescence as an explanation of organismal aging remains the subject of vigorous debate. The controversy relates, in part, to the fact that certain organisms (e.g., Drosophila, C. elegans) undergo an aging process, yet all of their adult cells are post replicative.

What is clear is that the loss of proliferative capacity of human cells in culture is intrinsic to the cells and not dependent on environmental factors or even culture conditions 18. Unless transformation occurs, cells age with each successive division. The number of divisions turns out to be more important than the actual amount of time passed. Thus, cells held in a quiescent state for months, when allowed back into a proliferative environment, will continue approximately the same number of divisions as those that were allowed to proliferate without a quiescent period 19.

The question remains whether this in vitro phenomenon is relevant to animal aging. One suggestive observation is that of fibroblasts cultured from samples of old skin undergoes fewer cycles of replication than those

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