New Concepts in Regulation of the Lifespan of Human Diploid Fibroblasts in Vitro
It was the initial observations of Swim and Parker (1957) on the longevity of human fibroblasts in cell culture, later confirmed and extended by Hayflick and Moorehead (1961) and Hayflick (1965), that have given rise to the discipline of cytogeronotology. That human embryonic fibroblasts demonstrate a finite lifespan in vitro has been taken as evidence for, and developed as a model system for, aging at the cellular level by a multitude of investigators following the pioneering work of Hayflick. Possibly no other single subdiscipline of cellular biology is more rampant with hypotheses offered to explain a given phenomenon than is cytogerontology. Although no single explanation has been uniformly derived or universally accepted regarding the mechanism of cellular senescence, the significance of the eventual answer has already been considered theoretically with respect to pathological implications (Goldstein et al., 1975; Timiras, 1975; Martin, 1979) and societal implications (Strehler, 1975). Some investigators question the extrapolation of data obtained from the classicalin vitro observations to the in vivo situation (see Orgel, 1973), while others question the phenomenon as being representative of cellular aging at all (see Bell et al., 1978). Whether the phenomenon (1) truly represents the normal sequence of events during cellular senescence, (2) is not aging but in reality is cellular differentiation, or (3) is simply an artifact of the conditions imposed upon cells in vitro will no doubt continue to be the subject of academic debate for years to come. That normal human diploid cells lose their ability to proliferate upon continuous subcultivation is not disputed.
KeywordsHuman Fibroblast Senescent Cell Human Diploid Fibroblast Population Doubling Level Human Diploid Cell
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