Longevity-associated mutations have been shown to lead to enhanced immune response including increased control of gene expression through RNA interference (RNAi) in somatic cells. Since it is known that RNAi is among the mechanisms underlying germline cells' enhanced resistance to pathogens and other stresses, the researchers examined whether the reactivation of germline genetic programs was involved in the extended lifespan of C. elegans mutants.
A series of experiments demonstrated that worms with increased longevity induced by mutations in the insulin-like signaling pathway did exhibit somatic cell expression of genes usually active only in germline cells. The mutant worms also were protected from stresses that damaged the DNA of non-mutant worms. The researchers also found that inactivating germline-expressed genes in the mutant worms eliminated the increased lifespan and that longevity-associated mutations in two genes from a different metabolic pathway one involved with detoxification and stress response also increased the expression of germline markers.
"The idea that somatic cells can reacquire genetic pathways usually restricted to germline cells is fascinating, and since germline protection is seen across species, the activity of these genes may play a role in controlling mammalian lifespan," says Ruvkun, senior author of the Nature paper. "Understanding the mechanisms involved in this transformation could help us develop new ways to repair and even regenerate key cells and tissues." A professor of Genetics at Harvard Medical School, Ruvkun was a co-recipient of the 2008 Lasker Award for Basic Medical Research for his role in discovering that tiny molecules of RNA can control the activity of critical genes
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Massachusetts General Hospital