Long-term effects of caloric restriction initiated at different ages on DNA polymerases in rat brain.

Caloric restriction (CR), has been shown to extend life span and delay both aging and the onset of a number of life-shortening diseases in laboratory animals. Defective DNA repair and DNA damage have been implicated as causal factors in many of these disease processes. CR appears to increase genetic stability by enhancing the DNA repair capacity and reducing the age-related accumulation of certain types of DNA damage. In the present study, we examined the effects of CR, imposed during four discrete periods of the life span of male Wistar rats, on the activity of total DNA polymerases of an aged brain which in turn may have a bearing on the process of aging. Our data indicates that CR had a greater stimulatory response on the activity of total DNA polymerases measured at 28 months of age in rats restricted from 6 to 28 months of age than in those restricted from postnatal day (PND) 7-21 which in turn was higher than those restricted from birth to PND 21. CR had differential effects in different regions of the brain. The enzyme activity of total DNA polymerases was significantly increased in hypothalamus and hippocampus. Cerebral cortex and corpus striatum are the regions which show no significant changes by CR regardless of age or duration of treatment while cerebellum registered a decrease during all periods of restriction. Modification of caloric intake alters total DNA polymerase activity and the extent of modification is both age and tissue dependent. Also, it appears that the effects of CR depend on when the paradigm is initiated, and are not solely a linear function of its duration.