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

CASTRO-PASCUAL, I; DAS NEVES OLIVEIRA, A; VAN HELVOORT LENGERT, A; MELENDEZ, M; CARGNELLUTTI E; ALTAMIRANO FG; FERRAMOLA, M.; LACOSTE MG; DELGADO SM; ANZULOVICH AC

MODALIDAD VIRTUAL

Congreso; XXXVI Congreso Anual de la SAN; 2021

Caloric restriction (CR) attenuates the aging process. The circadian molecular machinery and metabolismcommunicate through Sirtuins. SIRT1 plays a vital role in maintaining genomic integrity, through regulation ofthe BER repair pathway. We investigated whether in the Sirt1, Ogg1 and Ape1 expression have a temporalpattern in the rat cerebellum, the consequences of aging and the effect of a calorie restricted diet. MaleHoltzman: young (3-mo-old), old (22-mo-old) rats fed ad-libitum; and old-CR (22-mo-old rats fed at 40% calorierestricted diet for the last three months) were used. Sirt1 expression showed a circadian oscillation, peaking atnight in the cerebellum of the young, aging phase advanced the rhythm of Sirt1 (CT16:07±00:37 vsCT01:31±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 expressionshowed 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 theexpression of Sirt1, Ogg1 and Ape1 in the young rat cerebellum, which is altered by aging, and differentiallymodified by CR.