Proteins linked to longevity may be involved in mood control

Over the past decade, MIT biologist Leonard Guarente and others have shown that very-low-calorie diets provoke a comprehensive physiological response that promotes survival, all orchestrated by a set of proteins called sirtuins.

In a new paper that appeared online in Cell on 8 December, Guarente and colleagues have now shown that sirtuins likely also play a key role in the psychological response to dietary restriction. When sirtuins are elevated in the brain, as occurs when food intake is cut, mice become much more anxious. Furthermore, in two large genetic studies of humans, the team found that mutations that boost production of sirtuins are commonly associated with higher rates of anxiety and panic disorder.

The researchers believe that this anxiety may be an evolutionary adaption that makes animals - including humans - more cautious under the stressful condition of having to forage more widely for scarce food.

''It makes sense, because behaviour effects would be as adaptive, and as selected by evolution, as physiological effects. I don't think it's surprising that behaviour really falls under the umbrella of natural selection,'' says Guarente, the Novartis Professor of Biology at MIT.

The research suggests that anxiety could potentially be treated with drugs that inhibit sirtuins. On the other hand, it also raises a caution when treating patients with drugs that activate sirtuins, several of which are now in clinical trials for metabolic diseases, including diabetes. Those drugs can't enter the brain, but some researchers are exploring the possibility of using sirtuin inhibitors to treat neurological disorders such as Alzheimer's disease. If such drugs were developed and approved, doctors might need to watch for anxiety as a possible side effect.

Most of the experimental studies were performed in Guarente's lab at MIT, while the genetic studies were done primarily by collaborators at Virginia Commonwealth University and the University of Lausanne in Switzerland. Lead author of the paper is Sergiy Libert, a postdoc in Guarente's lab.