Robert K. Liu

Longterm dietary restriction and immune function in mice, response to sheep red blood cells and to mitogenic agents.

Abstract The humoral immune response to injection of sheep red blood cells and the responses of splenic lymphocytes to stimulation by three mitogens (phytohemagglutinin, concanavalin-A, and pokeweed) were compared between mice on a daily 21.6% casein/14.5 calorie diet and a population on half that amount from time of weaning. The mice were tested at 18–20 and 52–55 weeks of age. The results suggested that the more restrictive diet caused significant delay in maturation of the immune system. It is thus shown that a McCay type of dietary regime exerts a profound effect on the immune system. Whether this type of effect might be primary in the de-acceleration of aging classically associated with appropriate restriction of diet during childhood, or whether the immune changes are only tangentially related thereto is not yet established.

Survival and disease patterns in C57BL/6J mice subjected to undernutrition

This study reports survival and disease patterns in a long-lived mouse strain subjected to undernutrition. Four cohorts were studied, each composed of two or more groups of mice, each normally-fed or restricted either pre- and/or postweaning. Restriction prior to weaning was effected by limiting access to the mother. animals restricted postweaning received a nutritionally complete diet, including a normal complement of vitamins and salts, but were fed only 4 portions/week vs 7 portions/week for those animals normally fed—hence the term under-nutrition to differentiate between this and malnutrition. Comparisons of disease patterns among groups revealed that the incidence of lymphoma, the most prevalent tumor, was uniformly decreased in the groups restricted postweaning, with or without preweaning restriction. In the last cohort, deaths of animals with lymphoma were shifted to later ages in the restricted groups, compared with the normally-fed controls. Whereas the lymphoma pattern was considerably modified by undernutrition, the effect on overall survival did not seem as dramatic. Gompertzian parameters for survival past 120 weeks were not statistically different, although with one exception, maximum survival and one of the Gompertzian parameters was consistently greater in groups restricted postweaning, compared with those restricted preweaning only, or not at all. Maximum survival is a parameter not unduly influenced by environmental factors such as infectious disease; consequently, this represents a meaningful effect of undernutrition. Statistically, more significant differences in tumor patterns than in survival suggests that the former are more sensitive to undernutrition than is the latter—at least in this strain of mouse. Greater lifespan prolongation in the restricted animals may be possible through better “fine tuning” of the diet, including improved portion control, particularly in the early postweaning period, to prevent rapid weight gain, and possibly through changes in dietary composition. Finally, it is suggested that undernutrition may exert its effects through an alteration in gene expression.

The Effect of Lowered Body Temperature on Lifespan and Immune and Non-Immune Processes

The effect of lowered body temperature on lifespan and immune and nonimmune processes in invertebrates and vertebrates are reviewed. Decreasing the environmental temperature tends to increase lifespan of invertebrates and poikilothermic vertebrates. Thermolabile homeotherms appear to live longer than comparably-sized species which do not undergo periodic, natural lowering of their body temperature. Even a mild lowering of temperature suppresses both humoral and cellular immune processes in poikilotherms. On the other hand, metabolic and biochemical responses to decreased body temperature in poikilotherms are quite varied. With mild or moderate hypothermia (30–35°C), indications are that for most homeotherms, there would not be a major inhibition of nonimmune biochemical or metabolic processes. Initial studies aimed at inducing mild, chronic or intermittent hypothermia in mice with chloropromazine and marihuana derivatives are described.

Increased Growth and Life-span with Lowered Ambient Temperature in the Annual Fish, Cynolebias adloffi

FROM observations based primarily on natural populations, Bourlière1 was able to present evidence that lowered environmental temperatures slow the rate of growth and prolong the life-span of various fishes, amphibians and reptiles. No experiments, however, have been carried out to test the effect of ambient temperatures on both growth rate and life-span in poikilothermic vertebrates under controlled laboratory conditions. For such experiments it is desirable to have populations of short-lived animals which show senescence, and thus “annual” fishes would be suitable test subjects2.

Husbandry, life span, and growth rate of the annual fish, Cynolebias adloffi E. Ahl. ☆

Abstract The mean survival time of the annual fish, Cynolebias adloffi , maintained from hatching at 22°C, was 11-11·5 months, and the maximal survival time among this population of forty-four specimens was less than 14 months. These data plus results of gross and morphologic observation support the supposition that annual fish are relatively short-lived and undergo senile changes in about one years time. Suitable life tables of the same species maintained at 16°C were not obtained in this investigation due to the excessive incidence of tuberculosis encountered in this population. However, gross observation and measurements of egg production suggest that Cynolebias maintained at this temperature might show a decreased rate of aging as compared to those kept at 22°C. Growth rates at 16°C were considerably faster than at 22°C. Information regarding the care and breeding of annual fish is set forth.

Observations on the lifespans of several species of annual fishes and of the world's smallest fishes☆

Abstract Three species of South American annual fishes ( Cynolebias adloffi, C. bellottii and C. wolterstorffi ) were maintained in the laboratory at 15–16°C and 20–22°C. They grew faster, reached a larger eventual size and lived up to twice as long at the lower temperature range. Two species of gobies, collected as adults and representing the smallest known species of vertebrates, lived one to two years in the laboratory. The potential lifespan of these minute fish is probably greater than that of the annuals, suggesting that a strict relationship between body size and longevity does not obtain in teleosts.

Alterations in soluble/insoluble collagen ratios in the annual fish, Cynolebias bellottii, in relation to age and environmental temperature

Abstract Annual fish of the species Cynolebias bellottii have a prolonged survival when kept throughout most of their lives at 15°C, as opposed to 20°C. The prolonged survival is accompanied by changes in the ratio of soluble to insoluble collagen of such a nature as to suggest an actual retardation of the ageing process. It is known that reduced temperature in poikilotherms constitutes a potent immunosuppressive regime. The results are therefore consistent with theoretical expectations of the immunologic theory of ageing.