All animals, including humans, have an internal 24-hour clock or circadian rhythm that creates a daily oscillation of body temperature, brain activity, hormone production and metabolism.
Studying mice, researchers at Washington University School of Medicine in St. Louis and Northwestern University found how the biological circadian clock mechanism communicates with processes that govern aging and metabolism.
Reported March 19, 2009 through advance online publication in Science , their findings can potentially explain why the waning of the circadian rhythm with age could contribute to age-related disorders such as insulin resistance and type 2 diabetes.
"Our study establishes a detailed scheme linking metabolism and aging to the circadian rhythm," says one of the lead authors, Shin-ichiro Imai, M.D., Ph.D., who researches aging at Washington University School of Medicine. "This opens the door to new avenues for treating age-related disorders and ways to restore a healthy daily circadian rhythm. It could also yield new interventions to alleviate metabolic disorders such as obesity and diabetes."
Imai, associate professor of medicine and of developmental biology, focuses on the molecular mechanisms of aging and longevity. Earlier, he demonstrated that a gene called SIRT1 was at the center of a network that regulates aging. A form of the gene is found in every organism on earth, and seven forms of the gene exist in humans.
SIRT1 has a broad reach, influencing glucose breakdown and production, cholesterol metabolism, fat burning and insulin sensitivity. Basically, the gene coordinates metabolic reactions throughout the body and manages the body's response to nutrition.
Interestingly, increasing the activity of proteins related to SIRT1 extends the life span of organisms such as yeast, worms and flies. SIRT1 is activated when calories are restricted below normal, which has been shown to extend the life spans of some laboratory animals. "Under nutritional scarcity, SIRT1 may delay aging and extend life span to assure survival until food becomes more readily available," Imai explains.
Imai's collaborator in the current study, Joseph Bass, M.D., Ph.D., assistant professor of medicine and neurobiology at Northwestern University, earlier demonstrated that interfering with the circadian clock of mice led to metabolic complications including obesity and type 2 diabetes.
Now their joint research, led by Kathryn Moynihan Ramsey, Ph.D., at Northwestern and Jun Yoshino, M.D., Ph.D., and Cynthia S. Brace, both at Washington University, has linked the circadian clock to SIRT1 through a key metabolite that serves as the energy currency of the body.
As a result, they have defined a biochemical mechanism by which the body's metabolic and nutritional status can directly drive the oscillation of the body's daily clock as well as influence aging and longevity. This new information points potentially to innovative ways to correct metabolic disorders and improve health as people age.