科学家发现调整人体日常生理节律的机制

For Immediate¹ Release – Scientists from the Florida campus of The Scripps Research Institute have identified for the first time a novel mechanism² that regulates circadian rhythm（生理节律） , the master clock that controls the body's natural 24-hour physiological³ cycle. These new findings could provide a new target not only for jet lag（时差反应） , shift work, and sleep disturbances⁴, but also for disorders⁵ that result from circadian rhythm disruption, including diabetes⁶ and obesity⁷ as well as some types of cancer. The study is published in the November 12, 2010 edition (Volume 285, Number 45) of the Journal of Biological Chemistry.

"It's well known that the nuclear receptors RORα and REV-ERBα regulate expression of the gene⁸ BMAL1, which is vital to virtually every aspect of human physiology⁹ and a core component¹⁰ of the circadian（生理节奏的） clock," said Tom Burris, a professor in the Department of Molecular¹¹ Therapeutics at Scripps Florida who led the study. "BMAL1 functions as an obligate heterodimer（异质二聚体） (only working as a dimer with a partner) with either CLOCK or NPAS2 so it was unclear how RORa and REV-ERBa could control this complex. In this study, we show that both partners are targets. As we understand more about the relationship between these receptors and their gene targets, we can consider the possibility of modulating¹² the body's core clock, especially as we continue to develop synthetic¹³ ligands（配体） targeting these two nuclear receptors."

Circadian rhythms are conserved¹⁴ across a wide variety of organisms, from Drosophila (fruit flies) to humans. In mammals, these rhythms respond to light signals and are controlled by the "master clock" in the brain. In the periphery¹⁵（外围，边缘） , semi-autonomous clocks can respond to signals from the brain and from other cues including nutrient¹⁶ status. Disorders linked to dysfunctional circadian rhythms can be severe and potentially deadly, Burris said.

"When you're dealing¹⁷ with circadian rhythm, the most obvious disease target is sleep – for people who do shift work, critical jobs like police work, fire fighting, and medicine," he said. "If circadian rhythm is disrupted, you're prone¹⁸ to metabolic¹⁹ disorders like diabetes and obesity and even breast cancer – because the core clock is closely linked to the cell cycle. If your clock goes awry²⁰（失败，出错） , you run the risk of your cell cycle going awry as well."