title: Circadian Clock Control by Polyamine Levels through a Mechanism that Declines with Age.
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.
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Zwighaft
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Rona
authors.initials: R
authors.lastname: Aviram
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Moran
authors.initials: M
authors.lastname: Shalev
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Liat
authors.initials: L
authors.lastname: Rousso-Noori
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Judith
authors.initials: J
authors.lastname: Kraut-Cohen
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Marina
authors.initials: M
authors.lastname: Golik
authors.affiliation: Department of Biological Services, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Brandis
authors.affiliation: University of Düsseldorf, Medical Faculty, Institute of Clinical Chemistry and Laboratory Diagnostics, Düsseldorf, Germany; IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Reinke
authors.affiliation: Department of Plant and Environmental Science, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Asaph
authors.initials: A
authors.lastname: Aharoni
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Chaim
authors.initials: C
authors.lastname: Kahana
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: gad.asher@weizmann.ac.il.
authors.forename: Gad
authors.initials: G
authors.lastname: Asher
mesh_terms: D056930:ARNTL Transcription Factors / Q000378:metabolism*; D000375:Aging / Q000097:blood / Q000235:genetics; D000818:Animals; D056926:CLOCK Proteins / Q000378:metabolism*; D057906:Circadian Clocks / Q000235:genetics / Q000502:physiology; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology; D056931:Cryptochromes / Q000378:metabolism*; D005247:Feeding Behavior / Q000502:physiology; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D056950:Period Circadian Proteins / Q000378:metabolism*; D011073:Polyamines / Q000378:metabolism*
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; C538964:Cry1 protein, mouse; D056931:Cryptochromes; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D011073:Polyamines; D056926:CLOCK Proteins; C538944:Clock protein, mouse