Genetic Effects on the Longevity of Cultured Human Fibroblasts. III

Abstract

The level of heat-labile glucose-6-phosphate dehydrogenase (G6PD) has been measured in skin fibroblast cultures from premature ageing or DNA repair deficient genetic syndromes. The short in vitro longevity of Werner’s syndrome, progeria, Cockayne’s syndrome, ataxia telangiectasia, Fanconi’s anaemia, and Bloom’s syndrome cultures was correlated with the appearance of a significant fraction of heat-labile enzyme. Long-lived control cultures contain a low level of altered enzyme until they become senescent. The evidence that heat-labile G6PD molecules are derived from errors in synthesis, or from other causes, is critically assessed. It is shown that normal cells grown in medium containing the antibiotic, paromomycin, which is known to reduce the fidelity of ribosomal translation, produce a significant fraction of altered G6PD.

Effect of Malonate and <i>p</i>-Chlorophenoxy Acetic Acid on Hepatic Succinic Dehydrogenase Activity of Ageing Lizards

“…The test of antigenic properties to demonstrate the existence of cross-reacting material has also been successfully utilized [Reiss and Rothstein, 1975;Sharma et al, 1976Sharma et al, , 1979Schofield and Hadfield, 1978;Sharma and Rothstein, 1978;Holliday and Thompson, 1983], If the basic mechanisms of ageing pro cesses are similar throughout the animal kingdom, it is essential that the search be extended to a variety of species to accumu late evidence in favour of the concept. The view that altered enzymes accumulate dur ing ageing has received experimental support from studies in nematodes, insects, some mammalian species and cell cultures [Roth stein, 1979], thereby providing partial sup port to Orgel's [1963] error catastrophe hy pothesis.…”