Aging disrupts clock and epigenetic factors circadian rhythms and makes rhythmic the clock-controlled expression of DNA repair enzymes. Effects of a caloric restricted diet

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

Congreso; XXXVIII Annual Meeting of the Sociedad Argentina de Investigación en Neurociencias-SAN; 2023

Disruption of circadian rhythms and alterations in the DNA repair systems, constitutepart of the biological and molecular basis of motor and cognitive aging (Lacoste et al.,2017; Langie et al., 2017). Azis Sancar et al. (2015) reported that the DNA nucleotideexcision repair is regulated by the cellularclock. Given cerebellum is very susceptible to oxidative stress and DNA damage, weanalyzed the aging consequences on the circadian regulation of the DNA base excisionrepair (BER) system and the daily profiles of BER-related epigenetic factors, in thecerebellum. We also evaluated the effect of caloric restriction (CR) and investigated themechanism of Ogg1 and Ape1 circadian regulation. Three- and 22-mo-old rats treated ornot with a 40% CR diet and maintained under constant darkness, were used in this study.We observed that BMAL1 protein, as well as Sirt1 and Dnmt1 expression displaycircadian rhythms(p<0.05) in the cerebellum. Of note, Ogg1 and Ape1 expression isarrhythmic in this tissue. Aging disrupts clock and epigenetic factors circadian rhythmsand makes rhythmic the BER enzymes expression. CR partially restored the temporalpatterns. Transient transfection experiments showed that Ogg1 and Ape1 expression isregulated by the BMAL1:CLOCK transcription factor. We expect our results contribute tothe understanding of the circadian regulation of the DNA BER system and hownonpharmacological strategies could improve aging- related circadian decline in thecerebellum.