Compound is Key Coordinator of Clock and Metabolism

In a study of laboratory mice, researchers discovered the circadian clock genes strongly regulate the production of nicotinamide adenine dinucleotide (NAD), a critical cofactor involved in numerous cellular reactions and essential to energy utilization. In turn, NAD regulates the activity of an enzyme called SIRT1, which is a known key regulator of aging, metabolism and longevity.

This discovery -- that NAD and SIRT1 together function as a molecular “switch” to coordinate the internal clock with metabolic systems -- will help researchers better understand how aging, metabolism and the circadian clock are interconnected in living animals through this intricate molecular pathway.

“This is one of the sought-after links that couples changes with the cellular environment and nutrient state with changes in the internal clock,” said Joe Bass, M.D., Ph.D., a co-senior author on the paper and assistant professor of medicine and of neurobiology and physiology at Northwestern.

The researchers also found that levels of NAD oscillate, or move up and down according to the animal’s internal clock. This is the first evidence of a “metabolic oscillator,” an oscillating factor that is not part of the core clock machinery.

Research out of Bass’ lab a few years ago showed a clear link between disruption of the circadian clock with the development of obesity and the metabolic syndrome in mammals. The new findings help explain, in part, the molecular activity underlying those pathologies, says Bass.

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