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New link found between our body clocks, metabolism and aging

23 March 2009

By Dr Will Fletcher

Appeared in BioNews 500

A link has been found between the biological systems that govern aging and metabolism and those that control our daily cycles of feeding, activity and sleep. Researchers from Northwestern University, and Washington University School of Medicine, US, published their findings in the journal Science, and believe their results will have implications for the treatment of many metabolic and age-related diseases.

All animals have an internal 24 hour clock, known as the 'circadian rhythm', which causes a daily oscillation of brain activity, body temperature, hormone production and metabolism. The circadian rhythm is well understood at the genetic and molecular levels, but understanding of how it contributes to the health and disease of humans, and other animals, has remained elusive until now.

This new research uncovered a surprising link between metabolism and the circadian clock. The circadian clock genes were found to strongly regulate the production of nicotinamide adenine dinucleotide (NAD) - an enzyme that is involved in energy transport, and the release of energy from nutrients. NAD, in turn, regulates the activity of the enzyme SIRT1 which is known to be a key regulator of aging, metabolism and longevity. A form of SIRT1 is found in all organisms on Earth, and there are seven forms of the gene in humans that influence a wide range of tasks such as cholesterol metabolism, glucose breakdown and production, and fat burning and insulin sensitivity.

The key findings of this study hinged on the examination of laboratory mice by Joe Bass, an Assistant Professor of neurobiology and physiology at Northwestern University, and his colleagues. They discovered that levels of NAD were low and constant in mice with disrupted clocks but that in unaltered animals, even in perpetual darkness, levels of the enzyme fluctuated in tune with the circadian rhythm.

'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. This shows a direct connection - changes in the clock influence NAD.' It turns out that the opposite is also true - a deficit of NAD can negatively affect the clock. 'Perturbing the NAD pathway does affect the clock,' said Bass, adding: 'It does go in both directions.'

Bass warned that these results won't necessarily translate to humans but, if they do, 'this molecular knowledge gives us knowledge into diseases' such as sleep dysfunction, obesity and other metabolic disorders. That understanding could lead to new prevention tactics and therapies being developed in the future.

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