Studies of cellular ageing were first undertaken by Alexis Carrel nearly a century ago. Using newly developed cell-culture techniques, he questioned whether ageing occurred within individual somatic cells or only at the level of the whole organism. He erroneously concluded, because of limitations in experimental systems then available, thạt individual cells did nọt age and that, removed from the body, cells were immortal. This belief was not seriously questioned until the work of Hayflick in the 1960s. His seminal studies demonstrated that human fetal lung fibroblasts had a finite, reproducible life span and that, after 50~60 cumulative population doublings, they would cease to divide under culture conditions that initially supported exponential growth. He also noted that cells derived from older donors had a shorter culture lifespan. These results were soon confirmed by others, who also determined in adults an inverse relationship between dermal fibroblast culture lifespan and donor age, and a shortened culture lifespan for fibroblasts derived from patients with premature ageing syndromes compared to age matched controls. The general applicability of Hayflick's fibroblast findings (finite culture lifespan and decreased proliferative capacity at late passage or with advanced donor age) has since been confirmed in all cell types examined to date, including skin-derived keratinocytes and melanocytes.
From the above observations, Hayflick and others concluded that differences between early passage and late passage--cultured cells (in-vitro ageing) were closely related to differences between cells in tissues of young adults compared to old adults, and could thus explain age associated functional losses of medical significance. The in vitro model of cellular ageing specifically assumes that the same events thạt are responsible for in-vitro senescence also occur in vito and are responsible for clinical manifestations of ageing including, but not necessarily limited to, decreased cellular proliferative capacity as observed, for example, in slow wound healing. In view of the heavy reliance on this model system by gerontologists, relatively few data support this central tenet. Some investigators, including the authors, have therefore preferred to work with an in-vitro model of cellular ageing that compares cells of young adults with those of old adult donors at the earliest passage in which sufficient cells are available for study, in the belief that this comparison is more likely to reflect true age associated changes. Direct comparisons between the two models of cellular ageing have shown some differences between cells "aged" in vitro vs in vivo, and validity of both models remains a subject of discussion.
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