A Study of Low-Nutrient Diets Used for Aging Studies in the Rat

The effects of diets of low caloric value on rats used in aging studies were investigated. Groups of 85 Sprague-Dawley rats were fed ad libitum from 3 months of age on three different diets containing 8 or 10 Megajoule (MJ) of metabolizable energy and 80 or 100 g of crude protein/kg. Body weights, food consumption, and morphological and biochemical parameters were monitored throughout life. Kidneys were examined histologically. Rats given the diet with highest energy and protein ate less food, attained greater weights, and had larger abdominal fat deposits than those on the lower energy diets. They had a raised proteinuria, and nearly half developed glomerulosclerosis and tubulo-interstitial damage by 26 months. There was no significant difference in mortality between the groups, and no other serious abnormalities were observed. It is concluded that rats can be maintained into old age with no signs of nutritional inadequacy on diets with lower energy and protein contents than those in general use. T HE nutrient content of laboratory animal diets currently in use, though generally well able to sustain good growth and reproduction, is much more than adequate for maintenance. In the sheltered conditions of the laboratory, with a constant supply of food, laboratory rodents overeat, become obese, and are prone to nephropathies and neoplastic diseases that influence mortality and interfere with the objectives of long-term experiments. It is well known that restricting food intake has a life-prolonging effect (see review by Cohen, 1979), and several groups have shown that mortality and incidence of disease in laboratory rodents can be reduced by limiting food intake (Tucker, 1979; Conybeare et al., 1986; Masoro, 1988). Restriction can be imposed by rationing the animals to a given weight of food daily or, more simply, by allowing them free access to food for a limited time each day. Both systems are demanding of time and labor and may impose stress on animals whose natural habit is to eat small quantities of food over a long period. A more practical solution would be to compound a nutritionally adequate diet of reduced caloric value that could be fed ad libitum without inducing obesity and the attendant deleterious effects (Cohen, 1979; Coates, 1991). The work reported here was undertaken to explore this suggestion, with a view to the production of rats for studies of aging. Three diets of low protein and energy content were formulated from natural materials commonly used in commercial rodent diets. They were fed to rats from the age of 3 months, and growth, food intake, and morphological and biochemical parameters were monitored until the animals were more than 2 years old. Because aging in rats is commonly associated with development of chronic nephropathy, the kidneys of a representative sample of rats from each treatment were examined histologically at 12,