Fidelity in the Collagen Synthesized and Modified by Aging Fibroblasts in Culture

Abstract

It has been shown by Hayflick and Moorehead (1) and confirmed in other laboratories that diploid cell strains have a finite lifespan in culture. Lifespan is measured in the average number of population doublings before the so-called phase III or “senescent” state of the culture is reached. It is reasonable to propose that certain types of error continually or increasingly accumulated in the synthetic apparatus and reflected in each by increasingly defective proteins, may be causative of the “aging” of the culture. Such a concept has been proposed by Orgel (2) and preliminary evidence from Holliday and Tarrant (3) appears to lend support, although some controversy exists in the literature. In our estimation, the Hayflick phenomenon or the so-called “programmed death” of diploid cell strains allowed the planning of unique experiments in which error accumulation in proteins can be evaluated. The errors may be random, reflected in a generalized and increasing degree of protein imperfection, broadened or narrowed enzymatic specificity and increased thermal lability. Furthermore, one might expect significant changes in the responses to various metabolic controls of the type usually seen with larger enzymes composed of precisely tuned interacting subunits. The errors may not be entirely random in that certain sites may be particularly susceptible, to spontaneous changes, perhaps by a selection mechanism, and that aging, could be carefully orchestrated in movements in the sense that with increasing passage levels, defined off-on enzyme systems come into play. Perhaps both random and preordained changes occur simultaneously so that biological variation in the senescent phenomenon in regard to the average extent and average time course results.