The Regulation of Cellular Aging by Nuclear Events in Cultured Normal Human Fibroblasts (WI-38)

Abstract

Since the development of an in vitro model for aging in 1961, interest in the biology of vertebrate senescence at the cellular level has increased greatly. Previously it had been widely believed that normal vertebrate cells were immortal (1, 2), and consequently that biological aging was not the result of fundamental changes in the genome of individual cells. In 1961 we (3) demonstrated that normal human fetal lung fibroblasts have a limited proliferative capacity of 50 ± 10 population doublings, a finding that has since been confirmed in many laboratories. This limited proliferative capacity, and the physiological decrements that precede it, have been interpreted by us to be the in vitro counterpart of those processes that occur as an organism ages (3–6). Support for this hypothesis has come from many different studies demonstrating such phenomena as 1) an inverse correlation between population doubling potential of cultured cells in vitro and donor age (4, 7, 8), 2) a possible direct correlation between mean maximun species lifespan and in vitro proliferative capacity (9–15), and 3) a limited proliferative capacity for normal cells serially transplanted in vivo in syngeneic hosts (16–19).