Scientists have developed a compound called Mic-628 that advances the body's internal clock, potentially easing jet lag. In tests on mice, a single dose reduced adjustment time to a shifted schedule from seven days to four. The discovery targets a key protein to synchronize rhythms across the body.
A team of Japanese researchers has identified Mic-628, a compound that reliably shifts the mammalian circadian clock forward. Led by Emeritus Professor Tei H. from Kanazawa University, along with Associate Professor Takahata Y. from Osaka University, Professor Numano R. from Toyohashi University of Technology, and Associate Professor Uriu K. from the Institute of Science Tokyo, the group published their findings in the Proceedings of the National Academy of Sciences.
Mic-628 works by binding to the CRY1 protein, which typically inhibits clock gene activity. This binding promotes the formation of a molecular complex involving CLOCK, BMAL1, CRY1, and the compound itself. The complex then activates the Per1 gene at a specific DNA site known as the dual E-box, jump-starting daily biological rhythms. This mechanism synchronizes the brain's master clock in the suprachiasmatic nucleus with peripheral clocks in organs like the lungs, and it functions independently of dosing time.
To assess practical benefits, the researchers simulated jet lag in mice by advancing the light-dark cycle by six hours. Untreated mice took seven days to adapt, but those given a single oral dose of Mic-628 adjusted in just four days. Mathematical modeling confirmed that a feedback loop with the PER1 protein stabilizes this forward shift.
Advancing the clock—needed for eastward travel or early shifts—proves challenging compared to delaying it. Traditional methods like light therapy or melatonin require precise timing and yield inconsistent results. Mic-628's timing-independent action marks a novel pharmacological strategy.
Future studies will evaluate its safety and efficacy in more animal models and humans, positioning it as a potential treatment for jet lag, shift-work sleep issues, and circadian disorders.
