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Pass the cycloheximide

Worms with reduced protein production capacity live longer, according to Popi Syntichaki, Kostoula Troulinaki, and Nektarios Tavernarakis (IMBB, Foundation for Research and Technology, Heraklion, Greece). The reduction appears to save energy—energy that can be put to work in fixing life-threatening damage.

Protein translation rates decrease with age. Tavernarakis wondered if increased translation might increase turnover of damaged proteins and thus slow aging. But, he says, "what we found was the opposite."

The group knocked down the levels of IFE-2, one of the five isoforms of the eIF4E translation initiation factor in worms. The development and eating patterns of the worms were normal, but they had an extended lifespan.

Other longevity-promoting pathways, such as the insulin and caloric restriction pathways, may modulate the eIF4E pathway (e.g., caloric restriction may reduce protein synthesis by down-regulating eIF4E). But ife-2 knockout was additive with mutation of these other pathways, suggesting that a simple linear relationship is unlikely.

Animals with less eIF4E had higher ATP levels and were more able to resist oxidative damage. "If we reduce the rate of protein synthesis we allow the cell to invest some extra energy in maintenance and repair functions," says Tavernarakis. "By repairing damage the cells can now survive for longer."

This benefit is only relevant in the soma. In the germline, by contrast, translation is already near a minimum and a further reduction in eIF4E activity was lethal. "The germline invests in repair and maintenance but not so much in building," says Tavernarakis. "If we make our soma look a little more like our germline...then we might prolong the life of the soma."

Reference:

Syntichaki, P., et al. 2007. Nature. doi:10.1038/nature05603.

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 922K) Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?