Resetting the Circadian Clock
By Harry Goldstein


Sometime in the first half of the next century, we're going to select some brave humans, stick them in a highly engineered missile and shoot them at the planet Mars. The round-trip could take up to two years. During the journey, time itself will come to mean something other than it does on Earth. Figuring out what that something might be -- along with assorted other mysteries associated with how people exist in time -- is what keeps Dr. David Dinges up at night. It's what keeps his test subjects awake as well.
   Dinges is professor of psychology in psychiatry, chief of the Division of Sleep and Chronobiology and director of the Unit for Experimental Psychiatry at the School of Medicine. The laboratory he runs -- call it Starship Dinges -- is nominally located in a low-traffic area of the Hospital of the University of Pennsylvania (HUP), but functions as a world of its own. The floors rest on massive springs to minimize vibrations. Everyone speaks in hushed tones or whispers, so as not to disturb the sleep subjects. The lights are covered over with sheets of aluminum, resulting in an eerie semi-darkness in which less then one-twentieth as much illumination is available to the eye as in normal daylight. This lighting is kept constant, just as it would be on the first manned spacecraft heading for Mars, tentatively scheduled for 2014.
   The physiological effects of prolonged space flight are going to be formidable. NASA needs to know as much as possible about bone loss, muscle loss, radiation exposure, balance and motion problems, cardiovascular changes, immune changes, sleep-circadian changes and performance capability before any mission to Mars involving humans gets the green light. Toward that end, the National Space Biomedical Research Institute (NSBRI) formed a consortium led by the Baylor College of Medicine that includes Harvard, MIT and Johns Hopkins, as well as Dinges' lab at Penn. Dinges is associate director of the human performance, sleep and chronobiology team, whose mission is to determine how to optimize human physiology and brain function without the geophysical light/dark cycle of Earth and in the face of 24-hour operations on the spacecraft.
   To a visitor to the lab, a few days into the protocol the crew of Starship Dinges already look like they've been to the moon and back. Despite having gotten about eight hours of sleep over the course of the day (broken up into periodic naps), they seem haggard, glassy-eyed, with sallow complexions. The group currently in the lab has been randomly assigned to get a nap of one hour and 20 minutes in the afternoon. Their sleep is interrupted at night to study sleep inertia, the brain's reluctance to release the neurobiology of sleep -- in lay terms, wake up -- and function quickly and alertly. Dinges explains sleep inertia as the grogginess and disorientation that you feel when you've been awakened too soon from a deep sleep.
   Dinges' starship troopers live in an environment that simulates the space and environmental conditions of a spacecraft heading for Mars: The three male subjects sleep in one room, the single female subject in another. There is a large common space where the ersatz astronauts eat, work on batteries of tests and are evaluated physically. They have some free time to watch movies or play video games, and they're allowed to see newspapers -- which don't always come on the days they're dated.
   The subjects don't completely lose track of time, but lack the time cues that reset their physiology. One thing the researchers are looking at are circadian-mediated hormones: melatonin, cortisol and, most significantly for the purposes of the NASA study, growth hormone, three-quarters of which is secreted during slow-wave sleep. Sleep is disturbed radically in space. Every major study released in the last 10 years shows sleep periods are reduced from seven-to-eight hours to four-to-six hours. One of the major side effects of living in microgravity for prolonged periods is the loss of muscle and bone mass -- which explains the interest in the connection between growth hormone and the sleep system. It might turn out that sleep can be optimized to promote the secretion of growth hormone, which will keep astronauts healthier longer.
   The subjects are wired-up continuously to a small high-tech recorder they wear that measures their brain waves, heart rate, eye movements. and muscle activity, 24 hours a day. They also wear a rectal probe connected to a wrist-mounted sensor unit that measures their core body temperature and arm movements. Dinges insists that the discomfort level is fairly low, which the subjects themselves confirm. "Core body temperature is one of the best measures of the output of the suprachiasmatic nucleus in the hypothalamus -- the brain clock, the circadian clock," explains Dinges. "That's critical because we have to know what phase [subjects] are at in the circadian cycle to be able to understand what's happening to the rest of their physiology and brain function."




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