27 July 2015

Aging and RNA helicases

Suppression of HEL-1 helicase doubles the lifespan of roundworms

But no matter how hard we chase the dream of always staying fit and young, all our efforts end up the same, and we have to accept that we are mortal beings with a limited lifespan. There's nothing we can do to stop the aging process, and most of what people do only helps delay the inevitable: we can't stop death.

But if someone decided to try to stop her, what would be his first step? Scientists from the Plant Aging Research Center (Center for Plant Aging Research) of the Institute of Basic Science (IBS), Korea, have made a breakthrough in deciphering the aging process and in developing ways to dramatically slow it down.

Our body is programmed for rapid growth in youth and transition to adulthood, after which, at a certain age, the regeneration and restoration of our cells, tissues and organs slow down to a complete stop. All the mechanisms of this process are not yet fully understood, but researchers from IBS have made several significant steps towards understanding the regulation of cell lifespan.

They conducted a series of experiments with the roundworm Caenorhabditis elegans, whose cells, despite the small length of the animal (only 1 mm), have some qualitative characteristics in common with human cells. In C.elegans cells, they were interested in RNA helicases, a family of enzymes that regulate the function of RNA. RNA helicases are well known to science, but their role in the aging process has not been sufficiently studied. Director of the Plant Aging Research Center Hong Gil Nam focused his attention on the HEL-1 RNA helicase and found that inhibition of this enzyme contributes to the longevity of roundworms.

To determine which particular helicases they should pay special attention to, the scientists targeted each of the 78 RNA helicases. Noticing that changes in the genes of more than 30 RNA helicases usually result in a significant decrease in life expectancy, scientists realized that changes in far from any of the 78 RNA helicases would be suitable for increasing its duration. Each of the RNA helicases plays its own and important role, and each of them must be turned on or off separately.

The researchers worked with a mutant form of the worm, in which they limited the activity of the Daf-2 gene responsible for the rate of aging, reproductive development, resistance to oxidative stress, thermal tolerance, resistance to hypoxia and bacterial pathogens. In this case, changes in the Daf-2 gene led to a change in the insulin/insulin-like growth factor 1 (IGF1) signaling pathway (insulin/insulin-like growth factor 1 signaling, IIS). These Daf-2 mutants were characterized by increased resistance to various stresses, including heat stress, pathogenic bacteria and oxidative stress, and, most importantly, showed a double increase in life expectancy compared to the wild type C. elegans.

Hong Gil Nam and his colleagues believe that HEL-1 helicase may be one of the transcription regulators controlling how cells convert DNA into RNA, as other RNA helicases do the same. According to the scientists, "contrary to expectations that all RNA helicases have the same general function of "housekeeping" in RNA metabolism, our results show that RNA helicase HEL-1 plays certain roles in a certain pathway of longevity."

Even if immortality is not the immediate result of this work, there are other possible applications of this new information. Thus, in the frontal cortex of patients with Alzheimer's disease, levels of DDX39 (an analogue of HEL-1 roundworms in the mammalian body) are increased. The ability to regulate the levels of DDX39 and other RNA helicases can significantly help in finding ways to control Alzheimer's disease and other brain diseases.

Using the method of modifying RNA helicases to increase human lifespan looks promising, since both humans and roundworms have HEL-1 and IIS that can be manipulated in similar ways. Whether the same mechanism is responsible for the regulation of cellular aging in the human body is still unclear, but according to some data it is possible. The research of Korean scientists has not yet given mankind a cure for any diseases and does not promise life extension, but this is an important first step towards a more complete understanding of the life cycle and functions of cells.

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