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The University of Minnesota study finds a link between stress and circadian clock health

The human body has an internal biological clock that constantly works. Our well-being depends on the function of this clock. New research from the University of Minnesota Medical School has shown that low stress can make the circadian clock work better and faster.

Research over the past few decades has shown that our body has evolved a set of mechanisms, called the circadian clock, which internally drive the rhythms in almost every cell. The activity of the circadian clock is influenced by various signals in the cells.

In a recent study published in neuron, Dr n. Med. Ruifeng Cao, assistant professor at the Faculty of Biomedical Sciences of the Medical School and a team of seven laboratories in the USA and Canada focused on crosstalk between cellular stress signals and the circadian clock.

Cells respond to various stress signals by activating a signal transduction cascade that is centered on the eIF2α protein, which is a key factor that coordinates protein synthesis in cells. Cao and his team found that in the central clock of the brain, stress leads to rhythmic phosphorylation of eIF2α, which promotes the production of ATF4. The ATF4 protein activates the Per2 gene, which ultimately speeds up clock ticking. They came to the conclusion that this mechanism is necessary to maintain a solid clock, and therefore that stress signals affect the speed and reliability of the circadian clock.

It is known that the circadian clock breaks down in many diseases, but its cause is unclear. The discovery of Cao can provide insight into this unanswered question because it is the first connection between two basic processes in cells: stress response and circadian time measurement. One explanation may be that stress responses often break down in sick conditions, which in turn can break the clock.

The next step is a more accurate and detailed study of crosstalk between the cellular stress network and the circadian clock. We hope that our work can lead to the discovery of medicine that can control stress levels and regulate the function of the clock in disease, so that people are healthier. "

Ruifeng Cao, MD, PhD, Assistant Professor, Faculty of Biomedical Sciences, University of Minnesota Medical School


University of Minnesota Medical School

Magazine reference:

Pathak, S.S. et al. (2019) The eIF2α GCN2 kinase modulates the period and rhythm of the circadian clock through Atf4 translational control. Neuron. doi.org/10.1016/j.neuron.2019.08.007.

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