While the error theory of ageing has attracted most interest in recent times it cannot yet be regarded as being demonstrated. Posttranslational modifications of proteins explain many observed facts, but do not at present constitute a theory of ageing. The genetic theory appears logical but has little in vivo evidence to prove it. Basic mechanisms of ageing probably involve the interaction of several processes.
The purpose of this study was to assess sister chromatid exchange (SCE) levels and cell cycle kinetics in various murine tissues following MIC exposure. Following exposure of mice to MIC, these parameters were measured in bone marrow and alveolar macrophages labeled with BrdUrd in vivo and in peripheral blood and spleen lymphocytes cultured in the presence of BrdUrd in vitro. Target concentrations of MIC were 2, 15, and 30 ppm (3 hr).Neither elevated SCE frequencies nor inhibition of cell cycling were evident in lipopolysaccharide (LPS)-or concanavalin A (ConA)-stimulated spleen lymphocytes, or in LPS-stimulated peripheral blood lymphocyte (PBL) cultures from mice exposed for 3 hr to MIC concentrations as high as 30.5 ppm. Inhibition of cell cycling and poor culture success rates were apparent in ConA-stimulated PBLs following MIC exposures as low as 2.3 ± 0.4 ppm for 3 hr.At the lowest MIC dose employed, the cycling characteristics of bone marrow and alveolar macrophages were not altered, and SCE frequencies were at control levels. However, severe cell cycle inhibition was observed in these tissues at MIC concentrations of 15 ppm or greater. A marker of cytotoxicity at this dose was a high frequency (approximately 33-90%) of occurrence of first division cells containing a latereplicating Y chromosome.Despite its apparent cellular toxicity, MIC is not genotoxic as measured by SCE analysis in the tissues examined in this study.
Enzyme activities and immunological reactivities of seven different enzymes have been assayed in the polymorphonuclear leukocytes from 10 newborns, 10 aged (over 80 years old) and 10 young adults (20–30 years old). Polymorphonu-clears have been chosen because both in the newborns, and in the aged people, they are young cells whose life span is a few hours only. Five cytoplasmic enzymes have been immunologically studied by means of mono-specific antienzyme sera: leukocyte pyruvate kinase by immunoinactivation, glu-cose-6-phosphate dehydrogenase and glucose phosphate-isomerase by electroimmu-nodiffusion, lactic dehydrogenase (muscle-type) by radial immunodiffusion. Two ly-sosomal enzymes (α-mannosidase and β-glycuronidase) have been titrated immunologically with the same polyvalent antihuman leukocyte rabbit serum. Small but significant differences in activity were observed for several of the enzymes. By contrast, no significant difference was found, for any of the seven enzymes, as regards the ratio enzyme activity/immunological reactivity, between newborns, young adults and aged people. These results do not support the theory that a decreased accuracy of the protein synthesis machinery is responsible for aging and death. By contrast, the authors emphasize that the enzyme abnormalities reported by various authors in old animals or in old fibroblast cultures closely resemble those demonstrated to be ‘post-translational modifications’ in the case of human glucose-6-phosphate dehydrogenase.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.