Human sleeping and waking patterns are largely governed by an internal circadian clock that corresponds closely with the 24-hour cycle of light and darkness. This circadian clock also controls other body functions, such as metabolism¹ and temperature regulation. Studies in animals have found that when that rhythm gets thrown off（摆脱，关闭）, health problems including obesity² and metabolic³ disorders⁴ such as diabetes⁵ can arise. Studies of people who work night shifts have also revealed an increased susceptibility to diabetes.

 

A new study from MIT shows that a gene⁶ called SIRT1, previously⁷ shown to protect against diseases of aging, plays a key role in controlling these circadian rhythms. The researchers found that circadian function decays with aging in normal mice, and that boosting their SIRT1 levels in the brain could prevent this decay. Conversely, loss of SIRT1 function impairs⁸ circadian control in young mice, mimicking⁹ what happens in normal aging.

 

Since the SIRT1 protein itself was found to decline with aging in the normal mice, the findings suggest that drugs that enhance SIRT1 activity in humans could have widespread health benefits, says Leonard Guarente, the Novartis Professor of Biology at MIT and senior author of a paper describing the findings in the June 20 issue of Cell.

 

"If we could keep SIRT1 as active as possible as we get older, then we'd be able to retard¹⁰ aging in the central clock in the brain, and health benefits would radiate from that," Guarente says.

 

 

In humans and animals, circadian patterns follow a roughly 24-hour cycle, directed by the circadian control center of the brain, called the suprachiasmatic nucleus¹¹ (SCN), located in the hypothalamus.

 

"Just about everything that takes place physiologically¹² is really staged along the circadian cycle," Guarente says. "What's now emerging is the idea that maintaining the circadian cycle is quite important in health maintenance, and if it gets broken, there's a penalty to be paid in health and perhaps in aging."

 

Last year, Guarente found that a robust¹³ circadian period correlated with longer lifespan in mice. That got him wondering what role SIRT1, which has been shown to prolong lifespan in many animals, might play in that phenomenon. SIRT1, which Guarente first linked with aging more than 15 years ago, is a master regulator of cell responses to stress, coordinating¹⁴ a variety of hormone¹⁵ networks, proteins and genes¹⁶ to help keep cells alive and healthy.

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