Can we say that senescent cells cause ageing?

Replicative senescence, the irreversible loss of proliferative capacity, is a common feature of somatic cells derived from many different species. The molecular mechanisms controlling senescence in mammals, and especially in humans, have now been substantively elucidated. However, to date, attempts to link the senescence of cells with the ageing of the organisms they comprise has not met with any similar degree of success, largely due to a lack of systematic investigation and the absence of the necessary biochemical tools. This review will summarise current data linking replicative senescence and organismal ageing. It will also suggest some essential tests of the cell senescence hypothesis and some necessary ground work which must be carried out before such tests can be fruitfully performed. It will not discuss the detailed molecular 'clockwork' controlling the decision to exit the cell cycle irreversibly because this is covered by other authors in this special issue.