One of these days, the ability of our cells and tissues to regenerate and repair themselves will come to a stop. Researchers hoping to better understand the processes that regulate aging are studying a one-millimeter-long roundworm called Caenorhabditis elegans. These small, squishy guys share many cellular attributes with us. By making a few enzyme tweaks, a Korean team has doubled the lifespan of roundworms. Their findings were published in Proceedings of the National Academy of Sciences this week.
A large family of enzymes called RNA helicases are known to regulate both the generation and maintenance of RNA, which is found in all living cells. RNA (unlike DNA) is a single-stranded molecule, and it’s also necessary for key biological processes such as gene expression and protein synthesis.
To explore the role of RNA-regulating enzymes in aging, Mihwa Seo of the Institute for Basic Science and colleagues targeted and altered 78 helicases in C. elegans. Changing some of these actually decreased life expectancy. However, inhibiting helicase 1 (or HEL-1) promoted longevity in roundworms. The team thinks that HEL-1 acts as a transcription regulator, controlling how cells convert DNA to RNA.
The inhibition of RNA helicases leads to a longer lifespan in the roundworm Caenorhabditis elegans. Institute for Basic Science.
The team also altered a gene called daf-2 in the roundworms. The gene is responsible for the rate of aging, reproductive development, and resistance to bacterial pathogens, among other things. Their daf-2 mutant roundworms had double the lifespan of wild roundworms. These long-lived worms also showed an increased resistance to stresses ranging from heat to pathogens.
The mammal version of HEL-1 is called DDX39, and it’s found in increased levels in certain brain regions of Alzheimer’s patients. Being able to regulate DDX39 and other RNA helicases may help us to control brain disorders, and perhaps one day, the work could shed some light on human longevity.