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New research pinpointing the link between the body clock and metabolism may pave the way for scientists to treat an array of health problems, ranging from diabetes to sleep disorders.

In humans and other mammals, circadian rhythms, or the body clock, control everything from sleep to hormones. It is present – albeit less sophisticated – in life forms all the way down to plants and yeasts to ensure that important functions, such as cell regeneration, occur at the optimal time of the 24-hour day-night cycle. (It's also to blame for jet lag.) Scientists have long suspected that it is connected with metabolism (the way our bodies use energy), but they weren't sure exactly how.

In an attempt to unlock this molecular mystery, Joe Bass, an assistant professor of neurobiology and physiology at Northwestern University in Evanston, Ill., and colleagues wanted to see how the two functions might be related in mammals. They placed the mice – some with normal circadian rhythms and others whose rhythms had been disrupted – in complete darkness for 48 hours (in an effort to confuse normal body cycles). Their findings, published today in an online edition of Science: levels of the enzyme Nicotinamide adenine dinucleotide (NAD+), known to play a key role in metabolism, were low and constant in the mice with disrupted clocks but, even in perpetual darkness, levels of the enzyme in unaltered animals fluctuated in tune with daily cycles.

"Seeing this striking abnormality in the NAD levels was like discovering the cause of a disease in a patient after running a blood test," Bass said in a statement. "The pathway that controls NAD is tied to the clock at the most intricate level."

The research comes on the heels of a study published last week in the online edition of Science that paints a more detailed picture of what happens to trigger changes in NAD+ levels (it turns out to be a joint effort – of the aptly named circadian protein CLOCK and a metabolic gene called SIRT1). "When the balance of these two vital processes is upset, normal cellular function can be disrupted" Paolo Sassone-Corsi, lead author of that study and chair of pharmacology at University of California Irvine, said in a statement. "And this can lead to illness and disease."

These results won't necessarily translate to humans, Bass tells ScientificAmerican.com, but if they do, "this molecular knowledge gives us knowledge into disease" such as sleep dysfunction, obesity and other metabolic disorders. And that understanding could lead to new therapies and prevention tactics.

Image courtesy of iStockphoto/jhorrocks

2 Comments

1. 1. dberkholz 09:04 AM 3/23/09

   NAD+ isn't an enzyme. It is a coenzyme, which is a small molecule. It does not catalyze reactions independently but works work enzymes to do so.

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2. 2. dberkholz in reply to dberkholz 09:04 AM 3/23/09

   Works *with* enzymes, sorry.

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