Experimental 'gene switch' increases lifespan with no ill effects

By experimentally switching genes off or on at specific stages in an animal's lifecycle, UCSF scientists have discovered that vigor and lifespan can be significantly extended with no side effects. Many researchers believe that increasing lifespan will dampen reproduction. But the new study of the tiny roundworm commonly known as C. elegans shows that silencing a key gene only in adulthood increases longevity with no effect on reproduction.

The focus of the research is a set of genes that control a hormonal pathway. Since the same or a similar pathway is found in many organisms including humans, the results offer the tantalizing prospect of safely and effectively extending the human lifespan as well.

The research is published in the October 25 issue of the journal SCIENCE.

Many experiments in different organisms have supported the evolutionary principle that everything comes at a price that tweaking hormone levels to boost lifespan will inevitably cause abnormal reproduction. But in the new study, UCSF scientists report for the first time that the hormonal pathways controlling reproduction and longevity act independently and can be decoupled.

Typically, to study a gene's effect, researchers knock out the gene's activity permanently. But the scientists were able to use a new technique to turn genes off at different times and thereby learn that the genes had different effects at different stages in the life of the worm. They were also able to turn the "off" genes "on" again to further probe the timing of their influence.

The UCSF scientists studied a now well-known gene called daf-2. In previously research they showed that partially disabling the gene doubles the worm's lifespan. The gene encodes a receptor for insulin as well as for a hormone called insulin-like growth factor. The same or related hormone pathways have since been shown to affect lifespan in fruit flies and mice, and therefore are likely to control lifespan in h

Contact: Wallace Ravven
University of California - San Francisco

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