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Vitamin extends life in yeast, Dartmouth Medical School researchers find

able to elevate NAD with a small molecule before, Brenner said.

The team discovered two pathways that allow yeast to raise NAD levels with NR, improve their control of gene expression and live longer in the presence of high glucose. One of the pathways is new; the other was previously identified by Brenners lab.

At the molecular level, elevating NAD to turn on Sir2 actually enables the yeast to silence genes that are not supposed to be expressed. In any organism, not all genes are on at once; in yeast, there are sets of genes that Sir2 normally represses.

We showed that that we could improve Sir2-dependent gene silencing with NR and increase the longevity of yeast grown in high glucose conditions, Brenner said.

To test for Sir2 gene repression, the investigators found conditions in which wild-type cells cant accomplish normal gene silencing. Then, when they take up NR through one of the pathways Brenners team discovered, Sir2 gene silencing is restored, and yeast are rejuvenated. Yeast cells formerly capable of dividing 13 times, divided over 23 times when given NR.

Deletion of either pathway makes NR only half as effective as it is when both pathways are intact. So yeast cells seem to use both pathways equally well to lengthen their lifespan. The first NR pathway, described in 2004, consists of a gene common to yeast and humans. In fact, that gene is activated in damaged neurons in order to allow NR to protect against loss of axons. The second NR pathway involves three yeast genes, two of which are found in humans.

Granted that the human anti-aging apparatus is more complex, but animal studies indicate potential. Perhaps the best known sirtuin activator is the red wine compound resveratrol. Overfed mice on high dose resveratrol have healthier livers, better endurance and possibly longer lifespan. While resveratrol and NR work through different mechanisms to increase sirtuin activity, Brenner s
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Contact: Hali Wickner
hali.wickner@dartmouth.edu
Dartmouth Medical School
3-May-2007


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