Sirtuin-dependent clock control: new advances in metabolism, aging and cancer
Abstract
The circadian clock is an intricate biological timekeeper that is subject to fine-tuning mechanisms in order to maintain synchrony with the surrounding environment. One such mechanism is performed by the mammalian sirtuins that provide plasticity to the circadian clock by sensing cellular metabolic state. The sirtuins modulate the circadian epigenome and subsequent transcriptional control, and alterations to this organized system manifest in metabolic consequences, aging phenotypes and possibly cancer. New information regarding sirtuin-dependent control of the circadian clock has emerged. In addition to sirtuin (SIRT)1 and SIRT3, SIRT6 has been demonstrated as a critical regulator of circadian transcription that also serves as an interface with metabolic homeostasis. Also, new metabolic functions of SIRT1 have been described in the brain, which are critical to relay nutritional inputs to the central clock. This review focuses on the link between the circadian clock and the sirtuins, with an emphasis on new findings. In addition, speculation on the possible connections at the physiological level will be made that could further link the clock to aging and cancer.
References
Common light signaling pathways controlling DNA repair and circadian clock entrainment in zebrafish.
SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling
Citations
NAD metabolism and the SLC34 family: evidence for a liver-kidney axis regulating inorganic phosphate
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