For people who don’t get sleepy until 2 a.m., the buzz of an alarm clock can feel mighty oppressive.
Relief may be on the horizon, thanks to the discovery this spring of a genetic mutation that causes night-owl behavior.
Whether you’re a night owl or a morning lark rising effortlessly each day with the sun, your sleep habits are regulated by circadian rhythms. These internal clocks control just about every aspect of our health, from appetite and sleep to cell division, hormone production and cardiovascular function.
Like many who study the intricacies of circadian biology, I’m optimistic that one day we’ll be able to design drugs that synchronize our cellular clocks. Bosses frowning on tardy arrivals could soon become a thing of the past.
Our internal clocks
Nearly every cell in your body contains a molecular clock. Every 24 hours or so, dedicated clock proteins interact with one another in a slow dance. Over the course of a day, this slow dance results in the timely expression of genes. This controls when particular processes will occur in your body, such as the release of hormones like sleep-promoting melatonin.
Why are heart attacks and strokes two to three times more common in the early morning? Chalk that up to our internal clocks, which coordinate an increase in blood pressure in the morning to help you wake up. Why should teens listen to their parents’ pleas to go to bed? Because human growth hormone is secreted only once a day, linked to sleeping at night.
Nearly every biological function is intimately linked to our internal clocks. Our bodies are so finely tuned to these cycles that disruptions caused by artificial light increase our risk of obesity, chronic inflammatory diseases and cancer.
The timing of meals can also impact your health: When you eat may be more important than what you eat. Several years ago, a study looked at the feeding behavior of mice, which are nocturnal animals. When the mice ate a high-fat diet during their nighttime active phase, they stayed relatively trim. Those who nibbled on the same diet throughout the day and night became morbidly obese. Ongoing studies may soon show how this translates to human eating habits.
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What’s more, some 1,000 FDA-approved drugs target genes that are controlled by our internal clocks. That means the time of day that drugs are administered could matter. For example, some cholesterol-fighting statins are most efficient when taken in the evening so they can best hit their target, the HMG-CoA reductase enzyme.
Clock care 101
Our internal clocks are individually encoded, with most people falling in the middle range of a 24-hour cycle, but there are many outliers – including night owls – whose clocks are out of sync.
One in 75 people are predicted to have the “night owl mutation” in clock protein CRY1, delaying sleepiness until the wee hours. Not only does this make it harder for night owls to wake up in the morning, but their longer-than-a-day internal clocks puts them in a perpetual state of jet lag.
For night owls, the sleep cycle is largely beyond their control. But for the rest of us, there are steps we can take to rest easier and improve our health.
The clocks in individual cells are synchronized by the brain. The light that streams into the eye helps the brain’s “master clock” stay in harmony with the day/night cycle. That’s why, when you travel to another time zone, your internal clock no longer matches up with the solar cycle. It takes about a week to sync up to a new local time.
Bright artificial light at night tells the master clock that it’s still daytime, leading cellular clocks to race to keep up. That’s why seeing too much bright light at night can give you jet lag without going anywhere. One recent study found that simply viewing e-readers at night for a few hours can cause worse sleep and less alertness the next day.
You can minimize disruptions caused by artificial light by practicing good “light hygiene.” Expose yourself to plenty of bright light during the day and minimize your exposure to artificial light after dusk. These steps will help your internal circadian clock stays in sync with the light/dark cycle, promoting good sleep patterns and overall health.
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As we learn more about how circadian rhythms work, we’ll be better able to design therapeutic treatments that harness life’s natural rhythms.
In my lab, we study the complex molecular mechanisms that govern circadian rhythms. By looking at how CRY1 interacts with other clock proteins, we hope to understand how inherited mutations can wreak havoc on circadian rhythms. The night owl mutation in CRY1 appears to make it grab onto its partner proteins more tightly, like a bad dance partner who doesn’t know when to move on. When CRY1 doesn’t release its partner with the right timing, it delays the timing of everything controlled by the clock.
If we could understand these mechanisms better, it would set the stage for new drugs that could bring relief to a significant portion of the population. Perhaps we could shorten night owls’ internal clocks back to about 24 hours, helping them go to sleep at a “normal” time.
Given the complicated nature of biological timekeeping, there are likely many more genes that influence circadian timing. Imagine tailoring the timing of dosages to each patient’s circadian cycle, maximizing a medication’s impact while minimizing exposure to side effects. Picture patients checking their watch before popping a pill to treat high blood pressure or lower cholesterol. Ideally, one day our Fitbit-type devices will monitor our circadian rhythms, giving us precise real-time measures of our biological functions.
This may sound far-fetched, but it’s not that far off. Scientists are now searching for biomarkers that could be measured in blood to figure out internal clock timing.