The core circadian component, Bmal1, is maintained in the pineal gland of old killifish brain

Abstract

Circadian rhythm is altered during aging, although the underlying molecular mechanisms remain largely unknown. Here, we used the turquoise killifish as a short-lived vertebrate model to examine the effects of aging on the major circadian network comprising the four mammalian clock protein homologs, Bmal1, Clockb, Cry1b, and Per3, which are highly conserved in the killifish with 50%– 85% amino acid sequence identity to their human counterparts. The amplitude of circadian rhythmwas smaller in old fish (14 weeks) than in young fish (6 weeks). In old fish brain, the Bmal1 protein level was significantly downregulated. However, the Bmal1 interaction with Clockb and chromatin binding of Bmal1 to its downstream target promoters were retained. Furthermore, Bmal1 was relatively well maintained in the pineal gland compared with other regions of the old fish brain. The results suggest that the circadian clock system in the killifish becomes spatially confined to the pineal gland upon aging.