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

Summary

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 rhythm was 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.

Graphical Abstract

Highlights

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  The amplitude of free-running circadian rhythms decreases during aging in killifish

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  Core clock genes are highly conserved in the turquoise killifish genome

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  Bmal1 protein expression decreases in whole brain tissue with aging

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  Bmal1 expression is relatively well maintained in the pineal gland with aging

Abstract

Biological Sciences; Physiology; Molecular Biology; Chronobiology