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Researchers Pinpoint Link Between Caloric Restriction and Longevity
Date:9/20/2007

s very new knowledge about how NAD biosynthesis is regulated in our cells," said Dr. Shin-ichiro Imai, an assistant professor of molecular biology and pharmacology at the Washington University School of Medicine, in St. Louis.

The mammalian sirtuin family contains seven members, one of which, SIRT1, had previously been implicated in mammalian aging. "What we publish now is there are two more [sirtuins] that could lead to important drugs," Sinclair said.

"What's exciting is these genes make proteins that reside in mitochondria, and we discovered that if those genes keep mitochondria active, that's the gatekeeper of cell health," he added. "The cell can be essentially dead, but if the mitochondria and the sirtuins are active, the cells will live."

This suggests that if SIRT3 and SIRT4 could be chemically activated, it might be possible to achieve the benefits of caloric restriction without the diet. That could slow the progress of diseases based on cell death, such as Alzheimer's, cancer and diabetes, he said, and possibly extend life span as a result.

Sinclair said he is now looking for compounds that could activate SIRT3, and, as co-founder of Sirtris Pharmaceuticals, a drug development company that focuses on sirtuins, he is in a position to do so.

Imai was guarded on the question of whether pharmacologic activation of sirtuins is necessarily a good idea -- cell death is nature's way of eliminating severely damaged, and potentially cancerous, cells, after all.

"In general, there are benefits to increasing cell survival, but still we don't know precise details to this decision-making process," he explained. "So, I am very cautious about this. However, scientifically, I think this discovery is great, because it gives hope to us to develop a drug via the sirtuins."

Sirtris already has one sirtuin-activating compound in clinical trials. The company recently announced it was initiating early clinica
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