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Cell Metab. 2015 Nov 3;22(5):874-85. doi: 10.1016/j.cmet.2015.09.011. Epub 2015 Oct 8.

Circadian Clock Control by Polyamine Levels through a Mechanism that Declines with Age.

Author information

1
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel.
2
Department of Biological Services, Weizmann Institute of Science, Rehovot 7610001, Israel.
3
University of Düsseldorf, Medical Faculty, Institute of Clinical Chemistry and Laboratory Diagnostics, Düsseldorf, Germany; IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
4
Department of Plant and Environmental Science, Weizmann Institute of Science, Rehovot 7610001, Israel.
5
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
6
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: gad.asher@weizmann.ac.il.

Abstract

Polyamines are essential polycations present in all living cells. Polyamine levels are maintained from the diet and de novo synthesis, and their decline with age is associated with various pathologies. Here we show that polyamine levels oscillate in a daily manner. Both clock- and feeding-dependent mechanisms regulate the daily accumulation of key enzymes in polyamine biosynthesis through rhythmic binding of BMAL1:CLOCK to conserved DNA elements. In turn, polyamines control the circadian period in cultured cells and animals by regulating the interaction between the core clock repressors PER2 and CRY1. Importantly, we found that the decline in polyamine levels with age in mice is associated with a longer circadian period that can be reversed upon polyamine supplementation in the diet. Our findings suggest a crosstalk between circadian clocks and polyamine biosynthesis and open new possibilities for nutritional interventions against the decay in clock's function with age.

PMID:
26456331
DOI:
10.1016/j.cmet.2015.09.011
[Indexed for MEDLINE]
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