The team also examined mice that had no ability to produce SIRT1 in their brains. During diet-restricting conditions, these mice did not increase their activity, and their body temperature dropped more than normal, giving further evidence that SIRT1 was essential for high-activity, high-temperature responses.

As the researchers looked further into the role of SIRT1 in the hypothalamus, they found that during diet restriction, SIRT1 enhanced the production of a specific neural receptor in the hypothalamus involved in regulating metabolic rate, food intake and insulin sensitivity. Furthermore, mice with increased brain SIRT1 had a higher neural response to the gut hormone, ghrelin, which is known to stimulate the hypothalamus during low-calorie conditions. Both findings add weight to a significant role for SIRT1 in the hypothalamic response to a restricted diet.

The scientists are continuing to study the BRASTO mice to see if they live longer than ordinary mice.

Their work suggests that the brain, and particularly the hypothalamus, might play a dominant role in governing the pace of aging. They believe their studies could eventually provide clues for increasing productive aging in people.

"If we can enhance the function of the human hypothalamus by manipulating SIRT1, we could potentially overcome some health problems associated with aging," Imai says. "One example is anorexia of aging in which elderly people lose the drive to eat. It is possible that enhancing SIRT1 could alleviate behavioral problems like this."

SOURCE :  Washington University School of Medicine