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August 19, 2010

Gene’s action may help explain why restricting diet lengthens life and Enable Anti-Aging Drugs

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A team of University of Michigan scientists has found that suppressing a newly discovered gene lengthens the lifespan of roundworms. Scientists who study aging have long known that significantly restricting food intake makes animals live longer. But the goal is to find less drastic ways to achieve the same effect in humans someday. The U-M results offer promising early evidence that scientists may succeed at finding targets for drugs that someday could allow people to live longer, healthier lives.

In a study in the August issue of Aging Cell, U-M scientists found that a gene, drr-2, is an important component in a key cellular pathway, the TOR nutrient-sensing pathway, where many scientists are looking for potential drug targets. The U-M scientists then found that when they caused the drr-2 gene to be under- or over-expressed, they could lengthen or shorten lifespan in C. elegans, a worm widely used in research. Manipulating the drr-2 gene’s action produced the same effects as reducing or increasing caloric intake.

To find possible avenues for future anti-aging drugs, many scientists around the world are focusing on signaling pathways in cells that sense nutrients. The one Hsu examined, the target of rapamycin pathway or TOR pathway, is so named because its activity can be influenced by the drug rapamycin. Recent results from a large federal study being conducted at U-M and elsewhere have shown that in mice, rapamycin is effective at mimicking the anti-aging effects of dietary restriction.


Drugs tailored to block specific genes or proteins involved in nutrient-sensing pathways would have much more appeal than reducing what one eats. To achieve anti-aging benefits, it’s thought that people would have to restrict food intake by 30 to 40 percent, a grim prospect. In addition, drugs might be designed to avoid other disadvantages of this level of dietary restriction, which include reduced fertility

The study also found that drr-2 appears analogous to a human gene, eIF4H, that controls similar cell functions.

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