New gene-editing system enables large-scale studies of gene function.
While studies have shown that relatively large doses of the hormone melatonin can put people to sleep, MIT researchers now report that small doses which mimic the amount that normally circulates in the body also improves the sleep of elderly insomniacs.
Melatonin is produced by the pineal gland and is often called the "hormone of darkness" because it is secreted in humans and other species only at night. The hormone, whose function has puzzled researchers for centuries, may affect all sorts of circadian and seasonal body rhythms, such as day-night variations in body temperature and the onset of puberty. Melatonin has been shown to help "reset" the body's internal clock in blind people, those suffering from jet lag and in shift workers who work nights and sleep during the day.
In one of two related studies presented at the annual meeting of the Society for Neuroscience on October 25 in Miami Beach, Irina Zhdanova, principal research scientist in the Department of Brain and Cognitive Sciences, showed that increasing the amount of melatonin in their bloodstream can help elderly insomniacs, as well as children with the debilitating neurological disorder Angelman syndrome, get some shuteye.
In the human study, 30 people over age 50 with normal sleep or age-related insomnia received 0.1-milligram, 0.3-milligram and 3-milligram doses of melatonin or a placebo a half-hour before the time they usually went to bed. The researchers noted a significant increase in sleep efficiency and a reduction in wakefulness in insomniacs who received a 0.3-mg dose of melatonin.
This MIT group has previously shown that low doses of melatonin affect sleep in young people and can help children with Angelman syndrome to sleep through the night.
"We hope that our research will help people avoid potential short- and long-term side effects from melatonin treatment and identify people who might benefit from a melatonin supplement, as well as those who should be warned against increasing their melatonin levels," said Dr. Zhdanova.
She also said that one of the trickier aspects of choosing an appropriate dose of melatonin for use as a sleep aid is that "normal" melatonin levels vary widely among individuals and the same dose of the hormone can induce different levels depending on the individual's age or health. She recommends measuring individual melatonin levels, or, if this is not feasible, starting with a tiny dose (0.1 mg) and gradually increasing it until the desired effect is noticed.
The MIT researchers also were the first to report that nonhuman primates, whose sleep cycles and melatonin levels are similar to humans', are sensitive to the sleep-promoting effects of melatonin. Such animal models will allow researchers to study the mechanisms of melatonin's action on sleep and to uncover possible benefits or complications that may result from long-term use of the hormone.
Dr. Zhdanova and her colleagues have now provided further evidence that sleep in nonhuman primates is affected by low "physiological" doses of melatonin, and that a one-month treatment using such doses continues to help the monkeys fall asleep earlier and does not lead to an increased response to the substance or loss of its effectiveness.
The researchers are currently focusing on such issues as the dose dependency of melatonin's effects on sleep in monkeys and the effects of age-related changes in sleep and other physiological parameters on melatonin efficacy.
In any attempt to exploit melatonin's ability to modulate sleep or other body rhythms, it is critically important to consider appropriate doses and treatment, the researchers said.
"As you age, the amount of melatonin that your body secretes each evening decreases and the incidence of sleeping difficulties increases. I see melatonin as being potentially useful, particularly in those who don't secrete enough of the hormone," said Professor Richard Wurtman, a well-known melatonin researcher and program director for the Clinical Research Center.
This work was funded by the National Institutes of Health and the Center for Brain Sciences and Metabolism Charitable Trust.
A version of this article appeared in MIT Tech Talk on November 3, 1999.