Inhibitory effect of hypophysectomy and food restriction on glomerular basement membrane thickening, proteinuria and renal enlargement in aging male Wistar rats.

Age-related thickening of the glomerular basement membrane (GBM) was studied in three groups of male Wistar rats: (a) ad libitum fed, (b) hypophysectomized and (c) food-restricted eating the same amount of food as hypophysectomized rats, but about 45% of the ad libitum fed group. Studies were begun at 50 days (2 months) and continued throughout life. Multiple regression was used to statistically assess the effects of age and treatments. In ad libitum fed male rats GBM thickness increased from 114 nm at 50 days (2 months) to 632 nm at 1,000 days (33 months). GBM thickness at 1,000 days was 296 nm in hypophysectomized rats and 392 nm in food restricted rats. Hypophysectomy had a significantly greater inhibitory action on GBM thickening than food restriction, in rats eating the same quantity of food per day. However, a major part of the effect of hypophysectomy may be due to the permanent fall in food intake (from 16.3 to 7.9 g/day) resulting from the operation. Accompanying the age-related thickening of the GBM in ad libitum fed rats were proteinuria and renal enlargement, both of which were inhibited by hypophysectomy and food restriction.

Effects of isolation and food restriction begun at 50 days on the development of age-associated renal disease in the male Wistar rat.

The development of proteinuria with increasing age was studied in three groups of male Wistar rats: ad libitum fed and isolated, ad libitum fed and group housed 6 to 8 rats per cage, and food restricted (one-third of the isolated ad libitum food intake) and isolated. Studies were begun at age 50 days and continued throughout life. Ad libitum fed rats when isolated ate more food, grew faster, had larger maximum body weights and developed proteinuria at a faster rate than those that were group housed. There was a small increase in the severity of glomerular pathology in old age. However, systolic blood pressure was not affected significantly by isolation, nor was life duration. Food restriction of isolated rats inhibited body growth, prevented the development of proteinuria, reduced the incidence of glomerular and tubular pathology in old age and prolonged life. Electron microscopic examination of the kidneys of old food-restricted rats revealed a much lower incidence of foot process retraction and spreading on the basement membrane of the glomerulus than in ad libitum fed rats. Cardiac enlargement was also prevented by long-term food restriction.

The anti-aging action of hypophysectomy in hypothalamic obese rats: effects on collagen aging, age-associated proteinuria development and renal histopathology.

Hypophysectomy in young male Wistar rats aged 70 days, like food restriction begun at the same age, retarded the life-long rate of collagen aging in tail tendon fibres and inhibited the development of age-associated proteinuria and renal histopathology. Hypothalamic lesions which increased the food intake of hypophysectomized rats from 7 g to 15 g/day and produced obesity did not alter the rate of either collagen aging or proteinuria development, nor reduce life expectancy, but increased the incidence of abnormal glomeruli. In the intact rats elevation of food intake from 7 g to 15 g/day increased the rate of proteinuria development, but did not affect the rate of collagen aging. Hypophysectomy was found to have a greater anti-collagen aging effect than food restriction, when food intakes were the same in both groups. These studies suggest a pituitary-hormonal effect on collagen aging and a food-pituitary-hormone-mediated effect on the development of age-associated proteinuria.

Effects of caloric intake and dietary composition on the development of proteinuria, age-associated renal disease and longevity in the male rat.

The development of age-associated proteinuria and renal disease was studied in groups of male Wistar rats fed 12.5, 25, 50 and 75 kcal of food/day, respectively, and in calorie-restricted (40 kcal/day) rats receiving diets rich in fat, protein or carbohydrate. Proteinuria developed faster, kidneys were larger and the incidence of glomerular lesions and proteinaceous casts was greater in rats eating high calorie diets of 50 kcal/day or more. High protein diets, even when calorie-restricted, increased protein excretion and the incidence of glomerular lesions. In old rats acute food restriction (25 kcal/day) decreased protein excretion by 40% in 1 week, with no further reduction in the 2 week. Life duration was greatest in rats fed 50 kcal/day.