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

Ziv Zwighaft; Rona Aviram; Moran Shalev; Liat Rousso-Noori; Judith Kraut-Cohen; Marina Golik; Alexander Brandis; Hans Reinke; Asaph Aharoni; Chaim Kahana; Gad Asher

doi:10.1016/j.cmet.2015.09.011

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

Ziv Zwighaft, Rona Aviram, Moran Shalev, Liat Rousso-Noori, Judith Kraut-Cohen, Marina Golik, Alexander Brandis, Hans Reinke, Asaph Aharoni, Chaim Kahana, Gad Asher

Research output: Contribution to journal › Article › peer-review

119 Scopus citations

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.

Original language	English
Pages (from-to)	874-885
Number of pages	12
Journal	Cell Metabolism
Volume	22
Issue number	5
DOIs	https://doi.org/10.1016/j.cmet.2015.09.011
State	Published - 3 Nov 2015
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Inc.

Funding

We thank T. Tsimbalist, S. Meir, and I. Rogachev for the polyamines quantification and S. Ovadia for his help in bleeding the mice. We are grateful to U. Schibler for his valuable comments. The work performed in the G.A. laboratory was supported by the Israel Science Foundation (ISF 138/12), the Abish-Frenkel Foundation, the HFSP Career Development Award (HFSP CDA00014/2012), and the European Research Council (ERC-2011 METACYCLES 310320). G.A. and H.R. are funded by GIF collaborative grant (G-1199-230.9/2012).

Funders	Funder number
Abish-Frenkel Foundation	HFSP CDA00014/2012
European Commission	ERC-2011 METACYCLES 310320
German-Israeli Foundation for Scientific Research and Development	G-1199-230.9/2012
Israel Science Foundation	ISF 138/12

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10.1016/j.cmet.2015.09.011

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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.",

author = "Ziv Zwighaft and Rona Aviram and Moran Shalev and Liat Rousso-Noori and Judith Kraut-Cohen and Marina Golik and Alexander Brandis and Hans Reinke and Asaph Aharoni and Chaim Kahana and Gad Asher",

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AU - Kraut-Cohen, Judith

AU - Golik, Marina

AU - Brandis, Alexander

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AU - Aharoni, Asaph

AU - Kahana, Chaim

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

Abstract

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