Aging modifies the circadian rhythms of Sirt1 and DNA repair enzymes expression in the rat cerebellum Effect of caloric restriction

Abstract

Caloric restriction (CR) attenuates the aging process. The circadian molecular machinery and metabolism communicate through Sirtuins. SIRT1 plays a vital role in maintaining genomic integrity, through regulation of the BER repair pathway. We investigated whether in the Sirt1, Ogg1 and Ape1 expression have a temporal pattern in the rat cerebellum, the consequences of aging and the effect of a calorie restricted diet. Male Holtzman: young (3-mo-old), old (22-mo-old) rats fed ad-libitum; and old-CR (22-mo-old rats fed at 40% calorie restricted diet for the last three months) were used. Sirt1 expression showed a circadian oscillation, peaking at night in the cerebellum of the young, aging phase advanced the rhythm of Sirt1 (CT16:07±00:37 vs CT01:31±00:07, p<0.01), while in the old-CR, rhythm’s acrophase came near to control values (CT20:07±00:06, p<0.01). No circadian variation was found in the Ogg1 and Ape1 mRNA levels in the young, however, we observed maximal levels at CT4 and CT20, respectively (p<0.05). Ogg1 and Ape1 expression showed a circadian rhythm in the old, with the acrophase occurring at the beginning of the subjective day (CT01:57±00:11 and CT01:09±00:10, respectively). CR phases delayed Ogg1 and Ape1 rhythms in the old-CR (CT13:17±00:03 and CT07:41±00:35, respectively). Our conclusion is that there is a temporal variation in the expression of Sirt1, Ogg1 and Ape1 in the young rat cerebellum, which is altered by aging, and differentially modified by CR.