Circadian Clock Control by Polyamine Levels through a Mechanism that Declines with Age
Circadian Clock Control by Polyamine Levels through a Mechanism that Declines with Age
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DOI：
10.1016/j.cmet.2015.09.011
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发表时间：
2015-11-03
期刊：
影响因子：
29
通讯作者：
Asher, Gad
中科院分区：
文献类型：
--
作者：
Zwighaft, Ziv;Aviram, Rona;Asher, Gad
多胺是存在于所有活细胞中的基本聚阳离子。多胺水平是由饮食和从头合成维持的，随着年龄的增长，多胺水平的下降与各种病理有关。在这里，我们展示了多胺水平每天都在振荡。时钟和摄食依赖的机制都是通过BMAL1：Clock与保守的DNA元件有节奏地结合来调节多胺生物合成中关键酶的日常积累。反过来，多胺通过调节核心时钟抑制因子PER2和CRY1之间的相互作用来控制培养细胞和动物的昼夜节律。重要的是，我们发现，随着年龄的增长，小鼠体内多胺水平的下降与较长的昼夜节律期有关，而在饮食中补充多胺可以逆转这种情况。我们的发现表明生物钟和多胺生物合成之间存在串扰，并为营养干预防止时钟功能随年龄衰退开辟了新的可能性。
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.