The Search for the Body’s Keys to Time

Sunset/Sunrise in Space

No one really knows the details of how our body clocks work. But when the rhythms get messed up, the results can be horrendous. Accidents, loss of productivity, disease, including serious illnesses like cancer, are known to be caused, in part, by a messed up body clock.

“Biological clocks regulate almost every function in the human body,” said military physician Christian Macedonia, who is overseeing a biochronicity program at the Defense Advanced Research Projects Agency, or DARPA.

The timing and interplay of these clocks drive everything from cell growth to metabolism and from aging to death.

“If scientists can get a better grasp on how time factors into biological functions, the Department of Defense could potentially better preserve the health and readiness of the warfighter,” Macedonia wrote in an email to Discovery News.

It’s not just the military that would like the keys to the body’s timepieces. NASA, for example, has to figure out how to help people living off Earth. That mind-bending view from the International Space Station, which orbits about 240 miles above the planet, comes with a dizzying price: a sunrise and sunset every 45 minutes.

NASA is looking at practical solutions, like installing blue lights aboard the station, a wavelength which studies show increases alertness by suppressing the body’s release of melatonin, a natural sleep hormone, and stimulating the retinas to secrete an alertness protein called melanopsin.

The space agency’s interest in biological rhythm begins long before launch.

“One of the biggest areas we see it in is in travel, in jet lag. A lot of our folks are traveling — to Moscow, to Japan — before they go up in space for training,” NASA physician Smith Johnson told Discovery News.

“You can use bright lights and darkness to help your circadian shift, your internal clock that drives your circadian rhythm and we’re all different,” he said.

Under a $14 million DARPA research grant, Duke mathematician John Harer is working to reveal the underlying genetic networks that control the body’s various clocks.

“Inside a cell, when different genes are turned on, different things happen. One of the interesting things is that one gene will be expressed, or turned on, and that one will be involved in turning another one on, and then that one turns on another one a little bit later. Than it goes back and cycles back to the beginning.

“There’s this beautiful, complicated pattern of how one gene turns on another, or two or three genes work together and then that’s involved in turning on another. Not only do they keep the clock running, they also execute various kinds of instructions,” such as copying DNA prior to cell division, Harer told Discovery News.

“It’s an elaborate, very pretty dance, but it’s absolutely critical because when this goes wrong, that’s what cancer is all about, right? The cell division cycle isn’t working right, you get cancer,” Harer said.

The circadian clock, which is largely impacted by light and darkness, has similar mechanisms. Together, the biological clocks present a challenge — a mathematical one — to scientists trying to create models of what is happening and how the various systems work together.

“That’s where to you get to the possibility of explaining things, like why is it that people who have bad sleep patterns maybe are more likely to get certain kinds of diseases, like cancer,” Harer said. “Maybe there’s a coupling between the circidian clocks and the cell-cycle clocks. Or why is it that people who have sleep problems, also have metabolism problems?”

Accurate models would, in turn, guide the work of biologists looking for ways to restore, repair or enhance biological clocks.

DARPA says that could be key to helping soldiers in battle, improving trauma care and unraveling mechanisms of and treatments for disease.

“What makes DARPA’s program unique are both the approach it is taking and the scales. Chronobiology generally works at circadian, or 24-hour timescales. We are aiming to understand clocking from milliseconds to decades,” Macedonia wrote. “We do not want to just observe biological timing, but rather predict biological timing.”

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