Studies of aging in ames dwarf mice: Effects of caloric restriction

Abstract

Ames dwarf mice, which are small and deficient in growth homone (GH), prolactin (PRL), and thyroid stimulating hormone (TSH) live much longer (1-1.25 years) than their normal siblings. It was of interest to examine the response of these animals to caloric restriction (CR) because of the possibility that dwarf mice are voluntarily caloric restricted. We are testing the hypothesis that this possible natural caloric restriction will negate any benefits of an imposed CR on lifespan. Male and female Ames dwarf mice and their normal counterparts have been fed ad libitum (AL) or a 30% CR diet for 25-29 months. Animals were monitored daily and weighed weekly. At 12-15 months of age, CR mice weighed significantly less than their AL fed counterparts (normal females: -42%, normal males: -23%, dwarf females: -18.8%, and dwarf males: -22.2%). Only in dwarf females has this significant difference disappeared with age. At one year of age, a comparison of daily food consumption revealed that female dwarf mice consume significantly more food per gram body weight than normal females and a similar tendency is evident for males. Although they received 30% less food, CR mice ate the same amount as AL mice per gram body weight. On measures of total locomotor activity, CR mice were significantly more active than their AL-fed counterparts. On an inhibitory avoidance learning task, 18-21 month old dwarf mice exhibited significantly better retention than their age-and diet-matched normal counterparts. Histopathological analysis in aging dwarf versus normal mice suggested that the incidence of tumors does not differ between the two groups but tumors appear to develop later in dwarf than in normal mice. After 2.25 years on the study 27% of AL normals, 52% of CR normals, 74% of AL dwarfs, and 87% of CR dwarfs are still alive. We conclude that Ames dwarfs are not CR mimetics although they share many characteristics. It remains to be determined whether CR will delay aging and cause a further life extension in Ames dwarf mice.