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Caloric restriction (CR) extends life span and retards the onset of physiological changes and pathologies associated with aging, but the underlying mechanisms remain unresolved. This study demonstrates that CR postpones the documented age-related declines in and/or enhances the activity and microsomal concentration of several liver monooxygenases in male rats, i.e., NADPH cytochrome P-450 reductase, total cytochromes P-450. However, the relative concentration of cytochrome P-450b+C did not exhibit statistically significant changes, whereas another isozyme, the male specific P-450h, declined significantly in both ad libitum-fed and CR rats as a function of increasing age. While CR appears to retard age-associated changes in certain liver enzymes, this effect is by no means universal. The hepatic monooxygenases constitute a well-characterized enzyme system in which to examine the perturbation of the aging process by CR.

Age-related changes in hepatic fine structure were quantitatively evaluated in virgin and retired breeder (RB) male rats by morphometric analysis. Centrolobular hepatocytes increase in size, at least up to 480 days of age, and this increase is reflected in larger volumes of nuclei, cytoplasm, organelles, and ground substance. The surface area of the smooth-surfaced endoplasmic reticulum (SER) continues to increase with age in both groups of animals, although there is a significantly greater amount of both SER and rough-surfaced endoplasmic reticulum in the livers of the virgin rats. In addition, aging is accompanied by a gradual increase in the relative volume of the lysosomes and a linear decrease in the surface area of the Golgi membranes. Evidence from this study suggests that specific alterations in hepatic fine structure occur as a function of age.