Hyperadrenocorticism, attenuated inflammation, and the life-prolonging action of food restriction in mice

Food restriction (FR), which extends life span, is associated with an enhanced diurnal elevation of glucocorticoids. This increase in glucocorticoids may contribute to longevity by chronically enhancing the same protective mechanisms mobilized during acute stress. The objective of this study was to determine if attenuation of inflammation, a presumably protective effect of glucocorticoids, occurs in FR mice. Two-month-old male BALB/c mice were either fed ad lib (AL) or FR (60% AL calories) for 2 months. After one month, the diurnal elevation of plasma corticosterone was threefold higher in FR mice. Two weeks after corticosterone sampling, a hind foot pad of each mouse was injected with 20 μl of 4% carrageenan. Maximum observed edema did not differ between FR and AL groups, but edema was reduced at onset and fell earlier in FR mice. Results indicate that at least one inflammatory reaction is attenuated by FR and are consistent with the hypothesis that FR enhances a potentially protective glucocorticoid activity.