How drugs that hack our circadian clocks might one day improve our health

How drugs that hack our circadian clocks might one day improve our health
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We have more than one biological clock. The circadian clock, which sits in our brains, keeps our bodies in a rhythm. It is not the one that moves forwards with age. This clock controls when we sleep, eat, and wake up.

But there’s more to it than that. It also influences hundreds of molecular clocks in our cells and organs, which can influence the finer details of how our bodies function. There are clocks that regulate metabolism and others that control the production of proteins by genes. It’s not surprising that disruptions in our circadian rhythms can cause health problems, such as from jet lag and shift work.

Scientists are currently working to find ways to adapt treatments to our circadian rhythms. The lab is currently investigating drugs that target clocks. Were we able to hack the circadian clocks in order to improve our health?

Circadian clocks don’t tick forward so much as loop through cycles over a 24-hour period. They are basically clusters of genes or proteins that work together. For example, some genes might make proteins every day. These proteins can block genes from making new proteins overnight if they are made enough. When the levels of these proteins fall too low, the genes turn back on in the morning. The cycle continues.

These cycles are controlled by an internal clock, known as the hypothalamus’ master clock. This clock is believed to synchronize all of them. It is thought to have its own rhythm. However, it is affected by the amount of light entering our eyes, how we eat and sleep, as well as other aspects of our behavior.

Molecular clocks have been found to affect many biological functions. One study in mice found that 43% of the animals’ genes follow some kind of circadian rhythm. Most genes make more proteins in the “rush hours” between dawn and dusk.

It’s difficult to do the same research on people, but we know that many human genes work in a similar manner. Our hormones, and immune cells, seem to have a circadian pattern. They fluctuate throughout the day.

Even our microbiomes seem like they cycle over the course a day. Scientists analyzed stool samples taken from volunteers and found that certain types of gut bacteria are more prevalent during the day than others. The relative abundance of Bacteroidetes bacteria–which can break down starches and fibers in the gut–was 6% higher at night, for example. This is not yet clear, but it does seem that these patterns are disrupted in those with type 2 diabetes and obesity.

Both of these conditions are more common among people who work nights, who also have a higher risk of developing cancer and cardiovascular disease. Again, it’s difficult to work out exactly how much of this risk can be blamed on a disrupted circadian rhythm, but research suggests that working overnight can shift the timing of when some genes make proteins. These proteins are essential for the immune system, particularly those that kill cancer cells.

Given all this, it’s no surprise that the hunt is on for tools to realign our circadian rhythms. Some people swear by light therapy or melatonin. You can also influence your rhythms by changing your sleep and meals. Scientists are looking for drugs that target our molecular clocks directly.

Take KL001, for example. This compound can affect a protein called CRY. Clock genes can turn on the production of CRY. High levels of the protein can also cause the clock genes to stop working.

KL001 works to keep levels of CRY protein high, which can affect the length of the circadian period. This can have a knock-on impact on genes in the liver that follow a circadian rhythm. It can even control how liver cells make glucose, according to research on cells in a dish. This drug could theoretically help reduce the negative effects of shift work on metabolic health and lower the risk of developing diabetes.

Unfortunately, we are likely some way off from being able to do this in people. However, it’s worth looking into. We might be able, in the meantime to adapt existing treatments to individuals based on their circadian rhythms.

While we all roughly follow a diurnal 24-hour cycle, there are variations. People are thought to be influenced by their “chronotypes”, which determine when they feel awake, alert, and sleep. You can be either a morning or evening person. Some researchers believe that if we can determine the time a person uses to cycle through a day at the molecular levels, we might be in a position to help them decide the best time to perform surgery or deliver medicine.

Considering how long some of these ideas have been around, it’s a little disappointing that we haven’t made more progress. It’s an important area of research. You’ve likely all experienced the effects on your circadian rhythm. Jet lag can be very severe. You may feel tired and groggy the day after working late. While we all know that staring at screens at nights is bad for our health, how many of us can say that we don’t check our phones at night or in the morning?

We know that we should turn off our phones when it is time to go to bed and avoid artificial light at night. A regular bedtime and adequate sleep are two of the best ways to maintain good circadian health. At least it happens to be the best time of year for making resolutions …

To read more from Tech Review’s archive, check out these stories

Light pollution affects the health of plenty of living creatures, not just humans. And energy-efficient LED lights are making it worse, as Shel Evergreen found.

Disrupted circadian rhythms also affect astronauts in space, which could be linked to the organ complications and immune system deficiencies they experience, wrote Neel V. Patel.

Trying to get more sleep? Sleep-tracking devices might not necessarily help you, as my colleague Charlotte Jee found.

Or perhaps you want to cut down on screen time? The Human Screenome Project plans to provide insight into how we spend time on our smartphones–by screenshotting what we’re looking at every five seconds, as my colleague Tanya Basu reported last year.

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