In the early 2000s, researchers led by UCLA neurobiologist Ronald M. Harper detected brain-cell death and white matter injury in adult humans with OSA, in areas controlling not only cognitive functions but also mood, breathing, blood pressure and the nervous system’s ability to coordinate sensory information and movement. Meanwhile, Gozal’s team discovered that rats with simulated OSA, and children with the actual disorder, had elevated levels of inflammation markers that can presage cardiovascular problems. In a landmark 2007 study, they performed tonsillectomies on 26 kids with OSA who showed signs of vascular dysfunction; after the operations cured their sleep apnea, arterial tissue returned to normal in 20 of the patients.
Gozal’s team eventually found that children with OSA who also had specific gene variants were at particularly high risk for cognitive, cardiovascular or metabolic side effects. And in 2012, they uncovered the first evidence that sleep apnea influences epigenetics, altering gene expression without changing an individual’s DNA. In one kind of epigenetic change, known as DNA methylation, a methyl group (a carbon atom plus three hydrogen atoms) is added to a portion of DNA; it essentially flips a gene’s switch to the “off” position, shutting down the often-crucial function it performs. In children with OSA and elevated inflammation levels, at least one immune-system gene tends to be highly methylated. Hypermethylation can promote tumor growth; that may explain why, in a separate study, Spanish researchers in 2012 found higher rates of cancer among adult sleep apnea patients.
Although the damage caused by OSA comes partly from sharp fluctuations in oxygen levels as the patient fights for breath, much of the disorder’s devastation appears to result from its disruption of sleep. “We’ve separated those elements,” says Gozal. “Fragmented sleep alone is associated with inflammatory processes, oxidative stress and a variety of downstream consequences.”
Dealing With Deficit
Not all sleep deprivation, of course, is caused by disorders such as apnea. Many of us simply go to bed too late or have trouble falling asleep once we get there — a pattern we may repeat night after night. In 1999, University of Chicago endocrinologist Eve Van Cauter published the first study of the metabolic effects of that kind of chronic sleep deficit. At her lab, she restricted 11 healthy young men to four hours of sleep for six nights. For days afterward, the subjects metabolized glucose as poorly as pre-diabetics. Their blood cortisol, a hormone that rises with both stress and aging, reached levels common in much older men.
In later studies, Van Cauter and her colleagues found that men with a sleep debt developed higher levels of the hormone ghrelin, which stimulates the appetite, and lower levels of leptin, which suppresses it. Testosterone levels dropped as well. Such endocrine changes may help explain why epidemiologists have found elevated rates of obesity and diabetes among habitual short sleepers. “An animal will only deprive itself of sleep if it needs more time to forage,” Van Cauter observes. “So the body interprets sleep deprivation as a need to find more food.” In response, our hormones spur us to seek out edibles and store energy as fat.