Age fluctuations in mortality of mice with mutation causing growth retardation

Abstract

Lifespan of mice over a number of consecutive generations of descendants of a male with a mutation causing growth retardation was studied. The mutant and normally developing (normal) mice were obtained by crossbreeding of mutant males with normal females from the same brood. The mutant females were infertile. Mortality of the mutant and normal mice was shown to fluctuate depending on age. The curve of dependence of lifespan on their serial number in a series of lifespan increase (mortality rank curve) had the form of evident steps for the mutant mice, while in normal mice this feature was less pronounced. These steps indicate that in the course of development of mice stages with low mortality are alternately replaced by stages with increased mortality. One month after birth, the first stage of stable development of mutant males and females is replaced by a stage with abnormally high mortality, which coincides with the period of their maximal backlog in weight compared to the normal animals. Within two months, surviving mutants catch up in weight with normally developing mice and externally become indistinguishable from them. The steps are reproduced on mortality rank curves in mutant and normal mice, both in groups of mice of different sexes and in parallel same-sex groups. The observed phenomenon is interpreted within the hypothesis of a genetic aging program in mice that provides periodic changes when stages of great viability are followed by stages of increased sensitivity to the external risk factors causing death. Less-expressed steps on mortality rank curves of normal females were shown to be enhanced by the removal from the sample of parous females and animals with tumors. Results of the study indicate the possibility of detecting in humans of ontogenesis-programmed stages of high and low sensitivity to external influences and the prospect of the development of effective measures to prevent risks of premature death.