Aging, Nutrition and Hepatic Enzyme Activity Patterns in the Rat

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Abstract
A correlation between life expectancy of the rat and the levels of hepatic enzyme activity has been established. When the age-associated enzyme activity patterns were modified by dietary means, there were corresponding modifications in life span. This study of lifetime duration entailed approximately 1000 male rats divided into five dietary groups; the dietary variables were limited to the intake of protein, carbohydrate and calories. The hepatic enzymes investigated were ATPase, alkaline phosphatase, histidase and catalase, and the activities were determined at seven age periods ranging from 21 to 1000 days of age. The activities were expressed on the following bases: per unit weight (fresh, dry and fat-free), per unit nitrogen, per organ and per cell. From the cellular and enzymological data it was found possible to determine how much of the change in total enzyme activity, from one age to another, was directly attributable to change in number of hepatocytes and in volume of the hepatocytes. For each of the enzymes studied, the activity levels were found to vary with the age of the rat and with the diet fed. Similarly, the volume of the individual hepatocyte and the total number of hepatocytes also varied throughout the life of the rat and both were significantly influenced by the dietary regimen imposed. When parameters other than age were used as a basis of comparison, these discrete multiple patterns disappeared. The levels of activity of each of the enzymes, irrespective of age or diet, formed a single, continuous slope when related to nitrogen content, number of hepatocytes, hepatocytic volume, body weight and caloric intake. The progressive changes with age in the activity level of the organ or of the cell, represent an adaptation to the change in requirements of a larger animal or a larger cell. Rapid growth rates, structural or biochemical, are not commensurate with prolonged life span. The dietary regimen which evoked the greatest rate of change with age was most detrimental and such rats had the shortest life expectancy. With long-term caloric restriction, the levels of any of the biochemical constituents as well as of cell and animal size, were more like that of the young rat, and the longest life spans were obtained.