Caenorhabditis elegans, the roundworm in question, may not look much like humans since they measure just one millimeter in length, but a number of their biological processes are similar to ours. In the study, published this week in PNAS, the researchers turned their attention to a family of enzymes called RNA helicase. These enzymes are known to regulate RNA, which is found in every living cell to carry instructions from DNA to control protein synthesis and maintain cells. Though RNA helicase is well studied, researchers don’t know much about the role it plays in the aging process.
When the researchers suppressed one particular helicase, HEL-1, as well as a gene called daf-2, the mutated roundworms were not only more immune to environmental stresses of heat, cold and pathogenic bacteria, but also their lifespans were double that of wild roundworms.
They suspect HEL-1 plays a key role in how cells convert DNA to RNA, and even conscript other enzymes to do it too. “In contrast to the expectation that RNA helicases have general housekeeping roles in RNA metabolism, our findings reveal that the RNA helicase HEL-1 has specific roles in a specific longevity pathway,” the researchers write.
HEL-1 is found in humans. Some evidence suggest that HEL-1 could also have a longevity effect on humans.
RNA helicases are a large family of enzymes that regulate the generation and maintenance of RNA. However, the physiologic roles of RNA helicases in animal aging remained unknown. Here we show that an RNA helicase, helicase 1 (HEL-1), extends the lifespan of the roundworm Caenorhabditis elegans by up-regulating the longevity transcription factor forkhead box O (FOXO). Our finding suggests that an RNA helicase can have rather specific roles in animal longevity. A number of studies show that variants of FOXO are linked to human aging and longevity. In addition, the mammalian HEL-1 homolog has been implicated in cellular aging. Thus, our work may have direct implications in mammalian aging, and the human HEL-1 homolog may work with FOXO to increase lifespan.
The homeostatic maintenance of the genomic DNA is crucial for regulating aging processes. However, the role of RNA homeostasis in aging processes remains unknown. RNA helicases are a large family of enzymes that regulate the biogenesis and homeostasis of RNA. However, the functional significance of RNA helicases in aging has not been explored. Here, we report that a large fraction of RNA helicases regulate the lifespan of Caenorhabditis elegans. In particular, we show that a DEAD-box RNA helicase, helicase 1 (HEL-1), promotes longevity by specifically activating the DAF-16/forkhead box O (FOXO) transcription factor signaling pathway. We find that HEL-1 is required for the longevity conferred by reduced insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) and is sufficient for extending lifespan. We further show that the expression of HEL-1 in the intestine and neurons contributes to longevity. HEL-1 enhances the induction of a large fraction of DAF-16 target genes. Thus, the RNA helicase HEL-1 appears to promote longevity in response to decreased IIS as a transcription coregulator of DAF-16. Because HEL-1 and IIS are evolutionarily well conserved, a similar mechanism for longevity regulation via an RNA helicase-dependent regulation of FOXO signaling may operate in mammals, including humans.