The Drug That Resets Your Body Clock

Even if not jetting around the world in an exciting lifestyle, or working paramedic shifts at absurd hours, keeping a nice steady sleep schedule isn’t always easy.

Sometimes, it just takes one thing to crash it, and suddenly it can take weeks to get back to where you were (she writes, well past her bedtime, not to be a writer stereotype or anything).

So, what to do about it?

Mic-628

Researchers (Dr. Yuki Kasashima et al.) found a drug that might just fix it.

In her own words:

❝Here, we reveal that Mic-628 specifically and sufficiently induces Per1, provoking an abrupt phase advance in mouse behavioral rhythms, regardless of the timing of administration. Disruption of tandem E-boxes in the mPer1 promoter abolishes most of both mPer1 induction and phase-advancing activity, highlighting their role as unique binding sites for the CLOCK–BMAL1 complex. Mass spectrometry identified CRY1 as a potential target, with Mic-628 enhancing CRY1 binding to CLOCK-BMAL1, which tightly correlates with Per1 induction. Moreover, the autonomous PER1-mediated feedback repression likely explains the consistent phase-advancing profile. Overall, Mic-628 exerts its distinctive effect through precise molecular interactions that unveil an additional layer of transcriptional control within the circadian clock. This makes Mic-628 a promising therapeutic candidate for circadian disruptions.❞

In fewer words:

• What mic-628 does: it reliably advances the body’s internal clock by activating the core circadian gene Per1, which is unusually difficult to shift forwards.
• How it works: it binds to the CRY1 protein and reshapes the CLOCK–BMAL1 complex so it switches on Per1 via a specific DNA element called a dual E-box.

Translating that latter from sciencese: it’s an epigenetic switch by proxy.

If that’s not translated from sciencese enough and you’re wondering what an epigenetic switch is, then check out our recent article Switch Off Cancer Genes!, which covers it nicely.

This is a huge leap forward compared to approaches such as light therapy or melatonin, since Mic-628 advances the clock regardless of when it’s administered, removing a major limitation of current go-to methods.

For more on those two though, do see:

• Seasonal Affective Disorder & SAD Lamps
• Melatonin: A Safe, Natural Sleep Aid?

Another thing that Dr. Kasashima and her team found is that the drug advances timing in the brain’s master clock in the suprachiasmatic nucleus (a part of the brain) and in peripheral clocks, such as in the lungs, at the same time.

For anyone wondering what these other peripheral clocks are, you will enjoy: The Other Circadian Rhythms ← this is about what happens when your body parts clock on and off at the wrong time, because their internal clocks aren’t synchronized correctly with your master clock.

And, in terms of efficacy, they found that a single oral dose cut recovery from a 6-hour simulated eastward time shift from seven days to four days.

As you might expect, it’s still going through the necessary testing stages so it’s not available to the general public as yet, but what a boon!

You can read the paper itself, here: A Period1 inducer specifically advances circadian clock in mice ← yes, it’s a mouse study, but those are quite standard and almost always turn out to be the same when replicated in human studies, so this remains just as promising.

What to do meanwhile?

With regard to sleep, we’ve written so much about this, but here are three key articles that contain a lot of valuable information:

• Get Better Sleep: Beyond The Basics
• Calculate (And Enjoy) The Perfect Night’s Sleep
• Safe Effective Sleep Aids For Seniors

…as well as pointers to other relevant articles.

Sweet dreams!