University of Chicago Medical Center Aging alters sleep and hormone levels sooner than expected

Researchers from the University of Chicago report in the August 16 issue of JAMA that there are at least two stages of age-related deterioration of sleep quality and that, for men, the first stage occurs sooner than expected--between the ages of 25 and 45. They also found that changes in sleep were mirrored by changes in hormone secretion.

This was the first study to examine sleep quality and hormones influenced by sleep throughout adulthood, rather than comparing the sleep patterns and hormones of young versus old. The researchers collected data from sleep studies, conducted between 1985 and 1999, on 149 healthy men aged 16 to 83.

"Our study maps out the chronology of age-related changes in sleep duration and quality and suggests that altered levels of certain hormones may be a consequence of sleep decay," said Eve Van Cauter, Ph.D., professor of medicine at the University of Chicago and director of the study. "These changes in sleep quality provide an early biological marker of aging in men."

The first stage of deterioration of sleep due to aging occurs between young adulthood (ages 16 to 25) and mid-life (35-50). Although total sleep remained constant as young adults moved into mid-life, the proportion of slow wave or deep sleep decreased from nearly 20 percent of a normal night's sleep for those under 25 to less than five percent for those over 35. Growth hormone secretion, which occurs primarily during deep sleep, also declined by about 75 percent.

By the age of 45, note the authors, most men have almost entirely lost the ability to generate significant amounts of deep sleep. This study suggests that, as a consequence, most middle-aged men have very low levels of growth hormone.

Growth hormone deficiency has been studied extensively in the elderly, where it is associated with increased obesity, loss of muscle mass and reduced exercise capacity.

This study suggests that clinical trials of growth-hormone replacement therapy, which have previously been conducted in older men and women, might better target individuals in early mid-life. People over 65, who have already lived without the hormone for decades, may be less likely to respond and more likely to suffer adverse side effects.

"We begin estrogen replacement as soon as women enter menopause, not 20 years later," said Van Cauter. "If men go through 'somatopause' -- a loss of growth hormone -- between 25 and 45, why should we wait another 20 years to initiate treatment?

Another option is an indirect form of hormonal therapy, supported by recent studies in the Van Cauter lab and elsewhere, that involves using investigational drugs to stimulate increases in deep sleep. Increasing deep sleep triggers a proportional increase in growth hormone secretion.

The second stage of of deterioration of sleep due to aging occurs after age 50, during the transition from mid-life to late life. It includes decreased total sleep -- which declines by about 27 minutes per decade – more frequent and longer night-time awakenings, and a significant reduction in REM or dream sleep, to about 50 percent of young-adult levels. The loss of REM sleep appears to be associated with elevated evening levels of the stress-related hormone cortisol.

Cortisol is a 'fight or flight' hormone that heightens attention and alertness. Levels normally peak in the morning and decline during the day to very low levels in the evening, giving the system time to recover. Subjects with decreased REM sleep, however, had "an impaired ability to achieve evening quiescence," note the authors.

This lack of hormonal "down time," a recovery period for the stress-response system, has been linked to memory deficits and insulin resistance, a risk factor for diabetes. Elevated evening cortisol levels could also cause additional sleep loss. "Our data support the concept that decreased sleep quality contributes to the wear and tear resulting from overactivity of the stress-responsive systems," said Van Cauter.

By mapping out the effects of aging on sleep quality and hormone production, this study suggests new ways to intervene in the aging process.

"It is a tantalizing concept," said Van Cauter. "We are developing medications that can, in part, restore the capacity for deep sleep. If we could slow down the age-related changes in sleep quality, would that delay some of the many hormonal consequences of growing older?"

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Additional authors of the paper were Rachel Leproult, M.S., and Laurence Plat, M.D., both from the Van Cauter laboratory. The data were collected from a series of sleep studies; 109 subjects were studied at the University of Chicago and 40 were studied at the University of Pittsburgh, UCLA, or Pennsylvania State.

This research was supported by grants from the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, and by the Mind-Body Network of the MacArthur Foundation.