The Glucocorticoid Cascade Hypothesis of Aging and the hypothesis that food restriction retards the aging processes by preventing the development with age of hyperadrenocorticism were investigated. A longitudinal life span study of the daily concentration pattern of plasma corticosterone was conducted in male Fischer 344 rats fed ad libitum or restricted to 60% of the mean food intake of ad libitum fed rats. In another group of ad libitum fed and food-restricted rats, the influence of age on the response of plasma corticosterone levels to restraint stress was measured as was the time course of the return of plasma corticosterone to basal levels following the stress. The findings do not support the hypothesis that food restriction retards the aging processes by preventing the development of hyperadrenocorticism with advancing age. They also indicate that the Glucocorticoid Cascade Hypothesis does not describe a major aspect of the aging processes. Rather, the results suggest the possibility that a lifetime of daily periods of mild hyperadrenocorticism may, if anything, retard the aging processes.

No abstract

The mass of the perirenal adipose depot in male Fischer 344 rats increases between 6 and 18 months of age. This increase is due to an increase in the number of adipocytes in this depot, in contrast with the concept that adipocyte number is constant throughout adult life. The epididymal depot increases in mass between 6 and 18 months of age by adipocyte hypertrophy alone.

We examined the effects of breast and formula feeding during infancy on the serum llpoprotelns and on atherosclerosis in young adult baboons. Baboons were breastfed (n = 13) or formula-fed (n = 32) until weaning at 16 weeks of age and thereafter they were fed a diet containing 1.7 mg cholesterol/kcal and 40% of calories as lard until 5 years of age.

Using the baboon as a model, we tested the hypothesis that preweaning food intake influences the number of adipocytes at weaning. Two groups of 12 newborn baboons each were fed either a concentrated or a diluted Similac formula from birth to 18 weeks of age. Baboons fed the concentrated Similac were 38% heavier (P less than 0.01) and had 87% more fat mass (P less than 0.01) than the baboons fed diluted Similac. The mean adipocyte volume and adipocyte number were measured directly in 10 individual fat depots, and the total number of adipocytes were estimated for each baboon. The difference in fat mass was due to differences (P less than 0.01) in mean adipocyte volume, which was 0.22 nl in overfed baboons and 0.09 nl in underfed baboons. There was no significant diet effect on the estimated total number of fat cells; nor on 8 of 10 depots in which adipocyte number was directly measured. These results indicate that, in baboons, preweaning caloric intake has little or no influence on the number of fat cells at the age of weaning.

The extensive literature on the effect of rat age on the size and number of adipocytes in adipose tissue depots relates solely to young developing rats and young adults. Therefore a study was carried out in our laboratory on the cellular characteristics of the epididymal depot of the Fisher 344 strain of rats through virtually the entire life-span. Collagenase digests of this depot prepared from rats of 9, 13, 26, 52, 104, and 130 wk of age yield a population of cells with diameters greater than 30 mum identified as adipocytes or "fat cells." A remarkably complex pattern of changes in both the size and the number of these fat cells in the epididymal depot occurred through the life-span of the rats. The epididymal depots also contain some cells with diameters around 10 mum which have a morphology similar to that of the classic adipocytes; such cells may be preadipocytes.

Fischer 344 male rats were either fed ad libitum or 60% of the ad libitum intake. The restriction of food intake markedly increased the median length of life. Postabsorptive serum cholesterol and phospholipid concentrations increase in the ad libitum-fed rats with increasing age. Life-prolonging food restriction does not influence the serum levels of these lipids in young rats but delays the age-related increase in concentrations. Postabsorptive serum free fatty acid (FFA) concentrations decrease with advancing age in ad libitum-fed rats. Life-prolonging food restriction, while not affecting the serum FFA levels in young rats, delays and possibly partially prevents the age-related decrease in concentration. Food restriction lowers postabsorptive serum triglyceride levels at all ages studied. The data on serum cholesterol, phospholipids, and FFA provide further evidence that food restriction delays age-related changes in the physiological systems of rats. This delay of physiological decline may well retard the occurrence of age-related disease processes, thus prolonging life.

The hypothesis that infant overnutrition increases fat cell number and promotes obesity in the young adult primate was tested. Newborn baboons were fed similar volumes of Similac formulas with caloric densities of 40.5 (underfed, n = 8), 67.5 (normally fed, n = 12), and 94.5 (overfed, n = 12) kcal/100 g formula until 4 mo of age. Afterwards all baboons were fed the same diet until they were young adults. At 5 yr of age body composition, mean fat cell size, and total fat cell number were measured. Infant food intake did not significantly influence body composition or fat cell number in the 5-yr-old male baboons. Five-year-old female baboons, overfed as infants, had significantly greater body fat mass, percent of body mass that was fat, and mean fat cell volume compared with females that were underfed or normally fed as infants. There was no difference in total fat cell number between the obese baboons that were overfed as infants and the lean baboons that were underfed or normally fed as infants. Fat cell number was not associated with body fat content; males had more fat cells than did females. These results demonstrate that infant overnutrition in a primate species promotes obesity in young adult females by increasing primarily fat cell size and not fat cell number.