Think of sleep science, and you likely think of the brain. After all, while we're sleeping, we're mostly dreaming, and it's pretty clear where in the body that mechanism takes place. Scientists, too, have long emphasized the brain's role in how sleep works: what we know about our sleep cycles, restfulness, and circadian rhythms largely centers around neuroscience, and scientists going into sleep research assume as a matter of course that they'll be spending a lot of time watching sleeping brainwaves and prodding grey matter. But it turns out that we've been looking at sleep all wrong: your muscles, not your brain, might have a lot more to do with how well you sleep than previously thought.
Recently, UT Southwestern's Peter O'Donnell Jr. Brain Institute released data from an experiment that looked at whether a protein present in mice muscles had anything to do with how the mice slept and recovered from sleep deprivation. The protein, known as BMAL1, has been found to affect circadian rhythms before; it's found in more than 150 sites throughout the human genome, and studies have repeatedly found that it's got a strong role in what's called the body's "autoregulatory loop," or its internal molecular day-night rhythm.
We mostly understand sleep and its regulation to be an interaction between hormonal signals: cortisol, for instance, is associated with waking up, and melatonin with feeling sleepy (which is why melatonin is sometimes marketed as a sleep aid). The body's production of these hormones and others that contribute to sleep and wakefulness is regulated by its internal daily rhythms, our adrenal system, and other factors, but most of it is seen as a matter of bloodstreams and brainwaves. The problem is that looking at sleep this way may actually be leaving out a vital bit of the puzzle, and that has big implications for how we treat sleep disorders and understand everything from jet lag to snoring.
In trying to look at sleep beyond the role the brain plays, the scientists at UT found that the BMAL1 protein might have a bigger role than we previously thought. They knocked out the protein in certain mice muscles, and discovered that the mice had a pretty terrible time. They were less likely to have normal sleep, needed a lot longer to recover after a bad night's rest, and were inclined to sleep much deeper when they eventually reached dreamland. On the other hand, mice who had high levels of BMAL1 found it easier to recover from sleep deprivation.
The UT Southwestern scientists were hoping to find a potential therapy for people who have long-term sleep deprivation, like pilots or truck drivers, and playing with BMAL1 levels to raise them might provide a solution. But it's also an intriguing look at the bigger role that the body plays in sleep. Instead of just being a brain-hormone issue, it's embedded in our genes — and that's got big implications for understanding sleep and other illnesses.
According to a current research group at Tufts, BMAL1 is so fundamental to sleep and waking that, if you knock it out, the body tries to compensate with other biological factors but is completely thrown off. In 2008, a study found that if you eliminate the gene for BMAL1 in mice, both male and female, both genders ended up infertile. Other evidence suggests a strong link between circadian rhythm disruption and cardiovascular disease, diabetes, and psychiatric illnesses — but its relationship with cancer is the headline-grabber. "There is increasing evidence," wrote Dr. Christos Savvidis and Dr. Michael Koutsilieris in Molecular Medicine in 2012, "that links dysfunction of the clockwork with the pathogenesis of cancer."
Just like gut health, circadian rhythms are an area of human functioning that's increasingly revealing ripple effects in extremely unexpected places — and demonstrating their enormous importance. Circadian rhythms, it turns out, are so fundamental to so many parts of our health, that you can start studying how they work in sleep, and end up discovering something new about cancer.
So next time you can't get to sleep, instead of counting sheep, imagine a future where insomnia could be fixed by a simple dose of muscle protein. That's a dream that may in fact come true.