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Brain Protein Affects Aging and Sleep

A new study revealed how an aging-related protein in the brain affects sleep patterns. A better understanding of the connections between aging and sleep may lead to improved methods for treating or preventing certain diseases of aging.

Our sleep/wake cycle is governed by an internal circadian clock that’s coordinated by a tiny brain region known as the suprachiasmatic nucleus (SCN). The circadian clock adjusts to several cues in your surroundings, especially light and darkness. Animal studies have shown that disrupting the circadian cycle may trigger health problems, such as obesity and diabetes. In contrast, a stable circadian cycle that includes healthy, consistent sleep is associated with longer lifespans in mice.

Many people develop sleeping problems as they age. Recent studies have linked circadian activity with SIRT1, a protein known to be involved in the aging process. Researchers have been searching for ways to raise SIRT1 activity in hope of warding off age-related diseases. Strategies include calorie restriction and the compound resveratrol, found in grapes and wine.

To further explore the links between SIRT1 and the circadian clock, a research team led by Dr. Leonard Guarente at the Massachusetts Institute of Technology altered SIRT1 levels in the brain tissue of mice. Their study, funded in part by NIH’s National Institute on Aging (NIA), appeared in the June 20, 2013, issue of Cell.

The team created genetically engineered mice that produce different amounts of SIRT1 in the brain. They studied groups of mice with normal levels of SIRT1, no SIRT1, and 2 groups with increased SIRT1 — either 2 times or 10 times the normal amount. The researchers conducted “jet lag” experiments with the mice by shifting their light/dark cycles and observing their ability to adjust their sleep patterns.

Similar to previous findings, older mice with unaltered SIRT1 levels took much longer to adapt to shifting cycles than younger ones. Young mice lacking SIRT1 took twice as long to adapt as those with normal SIRT1 levels. Increasing SIRT1 levels, in contrast, had a protective effect. Old mice with 10 times the level of SIRT1 were able to adapt their sleep patterns much more quickly than normal SIRT1 mice of the same age.

A genetic analysis found that SIRT1 levels in the SCN affect the expression of genes involved in circadian control. All the circadian genes tested were expressed at significantly lower levels in mice lacking SIRT1. In contrast, the genes were expressed at higher levels in mice with more SIRT1. SIRT1 activated the 2 major circadian regulators, BMAL1 and CLOCK.

SIRT1 levels in the SCN declined with age in the mice — as did BMAL1 and other circadian regulatory proteins. These results suggest that SIRT1 plays a central role in the decline of circadian function as we age.

“What’s now emerging is the idea that maintaining the circadian cycle is quite important in health maintenance,” says Guarente, “and if it gets broken, there’s a penalty to be paid in health and perhaps in aging.” Further research will be needed to see whether dietary or other interventions that increase SIRT1 activity can help slow the onset and progression of sleep problems related to aging.

— by Meghan Mott, Ph.D.