From cells to ageing: a review of models and mechanisms of cellular senescence and their impact on human ageing

Given the duration of ageing in humans, cell culture studies are a promising approach to the study of human ageing. It is reasonable to assume that human ageing has, at least partly, a cellular origin. The question is how we can replicate in vitro the age-related changes that occur in human cells in vivo. In this review, widely used models for studying ageing in cell culture, such as Hayflick's, are interpreted in the context of the human ageing process. The mechanisms behind cellular senescence such as telomere disruption and DNA damage are reviewed and their relation to human ageing debated. A system-level examination of these mechanisms suggests that cell culture models are useful for studying cancer and certain age-related pathologies. There is little evidence, however, that cellular senescence is a significant factor in human ageing or that the mechanisms responsible for in vitro cellular senescence are a causative factor in human ageing in vivo. Therefore, novel approaches for studying human ageing at a cellular level are necessary and some suggestions are put forward. (C) 2004 Elsevier Inc. All rights reserved.