Intracellular determinants of cell aging.

Several important findings have been made since our observation that normal human and animal cells have a finite capacity to replicate and function. Among these are that: an inverse relationship exists between donor age and population doubling potential; more than 100 functional increments and decrements occur in cultured normal human cells before they age and die; normal tissue transplanted seriatim in vivo reveals a finite replicative and functional capacity; a direct relationship may exist between species maximum lifespan and population doubling potential of their cultured fibroblasts; the latent period increases as a function of age; cells from patients with accelerated aging syndromes undergo fewer population doublings than do age matched controls; and cultured fibroblasts from longer lived species have greater DNA repair capacity than do cells from species with shorter lifespans. Efforts to determine the location of the intracellular chronometer that controls these events has shown that the chronometer is intranuclear. The phenomenon of senescence has been found to be dominant over immortality.