Influence of short-term repeated fasting on the longevity of female (NZB×NZW)F1 mice

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Abstract

Caloric restriction in rodents is well known to retard the rate of aging, increase mean and maximum life-spans, and inhibit the occurrence of many age-associated diseases. However, little is known about the influence of short-term repeated fasting on longevity. In this study, female (NZB×NZW)F1 mice were used to test the physiological effect of short-term repeated fasting (4 consecutive days, every 2 weeks). The results showed that fasting mice survived significantly longer than the full-fed mice, in spite of the fasting group having a heavier body weight than the control group. Mean survival times for fasting and control mice were 64.0±15.3 and 47.9±9.4 weeks, respectively. Short-term repeated fasting manipulation was also effective on the prolongation of life-span in autoimmune-prone mice.

Introduction

Caloric restriction prolongs the mean and maximum life spans and inhibits age-related diseases in rodents (McCay et al., 1935, Fernandes et al., 1978, Kubo et al., 1984a, Kubo et al., 1984b, Kubo et al., 1987, Kubo et al., 1992a, Kubo et al., 1992b, Weindruch et al., 1986, Masoro, 1988, Weindruch and Sohal, 1997). Many experiments using this manipulation have been done to test the key concept of ‘undernutrition without malnutrition’. Although a number of hypotheses have been proposed, the precise mechanism responsible for this effect is not definitely understood. Fasting therapy was first used mainly for the treatment of obesity (Duncan et al., 1963, Drenick et al., 1964, Wing et al., 1983a), however, it has also been notably effective in the treatment of psychosomatic disorders, and is a common treatment for psychosomatic diseases in Japan (Yamamoto et al., 1979). Our experience with patients with allergic or gastroenteric diseases indicates that fasting therapy is very effective. To test our hypothesis that the effects of short term repeated fasting might also influence longevity or disease in rodents, we did an animal experiment using short-lived, autoimmunity-susceptible (NZB×NZW)F1 (B/W) mice, which represent one of several short-lived autoimmune-prone strains. Mice of this strain have been extensively studied as a model of human lupus erythematousus (Theofilopoulos and Dixon, 1986). These mice spontaneously develop autoimmune manifestations including formation of various autoantibodies and also develop a fatal immune complex glomerulonephritis. Profound influences of diet on development and expression of autoimmune disease in some strains of mice have previously been reported (Kubo et al., 1984a, Kubo et al., 1984b, Kubo et al., 1987, Kubo et al., 1992a, Kubo et al., 1992b). In B/W mice, life span has been doubled and sometimes even tripled by reduced caloric intake (Kubo et al., 1987), however, little is known about the effects of repeated fasting. In the present experiments, the effect of repeated fasting on body weight, immunological function and longevity is presented.

Section snippets

Mice

(NZB×NZW)F1 (B/W) mice were bred in our colony and weaned at 6 weeks of age. Specific pathogen-free conditions were maintained throughout the period of this study. The room was operated on a 12-h light/12-h dark cycle at constant temperature and humidity. At 6 weeks of age, female mice were housed in metal cages (five animals per cage) and randomly assigned to one of two groups, a repeated fasting group or a control group fed ad libitum, each group consisting of ten mice for the evaluation of

Growth curves

Mice were of two groups; a fasting group and a control group. The body weight of each group before, during, and after the first fasting time is graphed in Fig. 1. The body weight of the fasting group was significantly decreased as compared to the control group. However, the fasting group gained weight rapidly after refeeding started and became significantly heavier than the control group. Fig. 2 shows the lifetime growth of both groups. Weight was taken just before fasting. The most striking

Discussion

The present results show that the female B/W mice that repeatedly fasted had an increased length of the time before disease onset and had moderately prolonged longevity. It has been reported that, in all cases and regardless of calorie source, mice fed 60% of normal caloric intake lived from two to three times longer than their paired full-fed mice (Kubo et al., 1987). The effect of short term repeated fasting on longevity in rodents is not so noticeable as the effect of ‘undernutrition without

Acknowledgements

This study was partially supported by grants from Smoking Research Foundation.

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