In humans, genetic mutations usually lead to diseases or increased risk of them. But in the C. elegans roundworm, an induced mutation enabled a longer life span through the surprising transformation of “mortal” somatic cells into “immortal” germline cells. The study, funded in part by the NIA, was published recently in Nature.
Somatic cells, which are involved in an animal’s growth, metabolism, and behavior, have a limited life span. In contrast, germline cells continue from one generation to the next. In this study, researchers found that certain genetic mutations known to extend the lifespan of C. elegans induced somatic cells to express two genes that are normally active only in reproductive germline cells.
Normally, germline cells live longer than somatic cells, in part because they are more stable and better able to resist damaging stress. Here, the transformed somatic cells enabled the worms to live much longer than usual. The key was increased resistance to genotoxic stress, the result of new, protective insulin-like signaling pathways that preserved genomic stability, as well as enhanced RNA interference (RNAi). Conversely, the researchers found that inactivating germline-expressed genes in the mutant worms damaged DNA and shortened their normally long life span. “Taken together, these data suggest that soma-to-germline transformation, enhanced RNAi, and longevity share common regulatory mechanisms,” the researchers write.
The study, led by Dr. Gary Ruvkun of Massachusetts General Hospital in Boston, aids the understanding of molecular pathways involved in the genetic stability and longevity of mammals. It also may help scientists develop new ways to repair and even regenerate cells and tissues, which could lead to therapies that protect against age-related decline.