A life-span study was carried out on longevity, pathologic lesions, growth, lean body mass and selected aspects of muscle of barrier-maintained SPF Fischer 344 rats fed either ad libitum (Group A) or 60% of the ad libitum intake (Group R). Food restriction was as effective in prolonging the life of already long-lived SPF rats as previously shown for rats maintained in conventional facilities. Food restriction not only increased the mean length of life but also acted to extend life span since more than 60% of the Group R rats lived longer than the longest lived Group A rat. Renal lesions occurred at an earlier age in Group A rats than in Group R rats and progressed more rapidly. Death of most Group A rats was associated with severe renal lesions while few Group R rats showed such lesions at death. Food restriction was also found to delay or prevent interstitial cell tumors of the testes, bile duct hyperplasia, myocardial fibrosis and myocardial degeneration. Gastrocnemius muscle mass declined in advanced age and food restriction delayed this decline. Interestingly, however, lean body mass did not progressively decline with increasing age but rather decline occurred only after the onset of the terminal disease process.

Male Fischer 344 rats were either fed ad libitum (Group A) or 60% of the ad libitum intake (Group R) starting at 6 weeks of age; the latter is a life prolonging food restriction. Total adipose mass increased with increasing age in both Group A and Group R rats until about 70% of the life span after which it declined. The results indicate that the lower adipose mass of the Group R rats is probably not related to life prolongation. Adipocyte hypertrophy is involved in growth of the epididymal and perirenal depots in adult Group R rats and is the sole basis of epididymal depot growth in adult Group A rats. Increasing adipocyte number is the sole basis of perirenal depot growth in adult Group A rats and is involved in the growth of both depots in adult Group R rats. Decreasing adipose mass during senescence involves decreasing mean adipocyte volume but not a decrease in the adipocyte number.

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Food restriction has long been known to prolong life in rodents, and recent studies have shown it to have antiaging effects in regard to a variety of physiologic and pathologic processes. It has been suggested that these actions of food restriction relate to the reduction of metabolic rate per unit of body mass brought about by this dietary regimen. Data are presented in this report showing that food restriction can have a marked life-prolonging action in rats without reducing caloric intake per gram of body weight. Moreover, the food-restricted rats consumed a greater number of calories per gram of body weight during their lifetimes than did the rats fed ad lib, yet they lived longer. Thus, the data in this report do not support the concept that food restriction slows the rate of aging by decreasing the metabolic rate.In his 1977 review surveying life-prolonging experimental procedures, Sacher (1) concluded that the well-established life-prolonging antiaging action of food restriction in rodents is due to a reduction in the rate of metabolism per unit of body mass. Sacher based this conclusion on an analysis of data from a study performed by Ross (2) in which rats were provided five different dietary regimens resulting in caloric intakes ranging from 18 to 75 kcal/day. The average survival times varied among groups (ranging from 780 to 990 days) and were found to be inversely correlated with the daily caloric intake of the rat. However, when Sacher (1) calculated total caloric intake during the life span per gram of body weight, he found that it was almost the same for each of the five dietary regimens; the average was 102 kcal/g of body weight, and none of the means for the five dietary groups differed from the average by more than 4.5%. Thus, the lifetime caloric consumption per gram of body weight was nearly constant; this indicates that food restriction prolongs life by increasing the time required to reach this total.Research just completed in our laboratory on the effects of food restriction on specific pathogen-free male Fischer 344 rats does not support the conclusion of Sacher regarding the basis of the life-prolonging action of food restriction. In our study, food restriction markedly prolonged the length of life, slowed the progression ofage-related disease, and delayed age-related physiological deterioration but did not influence caloric intake per gram of body weight in the manner predicted by Sacher. The details ofour research in regard to longevity and age-related disease have been published elsewhere (3), and the data on the effects of food restriction on age-related physiological deterioration have been recently reviewed (4). The data on the relationship between food restriction and total life-span caloric intake per gram of body weight are the subject of this report. MATERIALS AND METHODSMale, specific pathogen-free Fischer 344 weanling rats (28 days old), purchased from Charles River Breeding Laboratories, were singly housed in bonneted cages in our barrier facility. For the first 2 ...

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