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German scientists reveal the great secret of eternal youth


What makes us age? - The secret of youth
Researchers at the Institute for Molecular Biology (IMB) in Mainz have made a breakthrough in research into the aging process. The scientists were able to demonstrate that genetic factors can slow aging. However, these factors cause the process to speed up in advanced age.

In the nematode of the Caenorhabditis elegans species, Dr. Holger Richly and his colleagues discovered genetic factors that slow aging in young animals but accelerate them in advanced age. Surprisingly, the genes identified control the intracellular process of autophagy, which breaks down cell components that are no longer functional and is generally attributed to health-promoting properties. The research results were recently published in the scientific journal “Genes & Development” and provide first indications of how the aging process emerged as an inevitable by-product of evolution.

In their publication, the scientists show that the lifespan is prolonged when the autophagy process in older animals is down-regulated, which leads to the maintenance of healthy nerve cells and generally to an improvement in health. These new findings could also be of importance for the treatment of neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's chorea, in which the autophagy process also plays a role.

Every human being and almost every species on our planet ages. However, the question is: why? According to Charles Darwin's theory of evolution, natural selection means that creatures that adapt optimally to a habitat have greater chances of survival and pass on their genes to future generations. The more successfully the properties of certain genes support reproduction, the more will be selected for these genes. On this basis, George C. Williams developed an antagonistic pleiotropy (AP) in 1957, a hypothesis of aging that evolution selects genes that are beneficial in adolescence and reproduction, but have negative effects in old age. Although this theory is supported by mathematics, there has been little experimental evidence to date that genes behave according to this hypothesis.

In their publication “Neuronal inhibition of the autophagy nucleation complex extends lifespan in post-reproductive C. elegans”, Dr. Holger Richly and his laboratory at the IMB in Mainz showed that many genes show AP behavior and thus greatly accelerate the aging process. Although the research team examined only a fraction of the Caenorhabditis elegans genome with 800 of around 20,000 genes, the scientists were able to find a very remarkable number of 30 genes that behave according to the AP theory. “When you consider that we only tested four percent of all worm genes on our screen, we can assume that many other AP genes can be identified,” emphasizes Jonathan Byrne, a former PhD student in Dr. Holger Richly at the IMF and one of the two main authors of the study.

"Evidence that aging is driven by evolution was not the only surprise in our research," added Thomas Wilhelm, co-lead author of the publication. "What surprised us most was the knowledge of the fundamental biological processes in which the identified genes are involved." The scientists found that autophagy, which is an essential cellular recycling process that is normally required to maintain vital functions and longevity, shows very strong AP behavior. "At this point, our research became really fascinating," said Dr. Holger Richly, research group leader at the IMB and project leader of this study. The autophagy process is known to function less and less with age, but the study's authors show that it is completely inoperative and even harmful in older worms. The molecular biologists were able to show that down-regulation of key genes that initiate the autophagy process leads to a dramatic extension of the lifespan.

"These results should make us think and lead us to critically review our theories about autophagy," concludes Dr. Holger Richly explains: “So far, autophagy has almost always been seen as beneficial, even if it hardly works. In contrast, we show the serious, negative consequences that can arise when autophagy gradually breaks down late in life, and that it would probably be better to avoid autophagy in old age. This is classic antagonistic pleiotropy: in young worms, autophagy works perfectly and is essential for the development of the living being, but after reproduction, it becomes defective and causes the animals to age. ”

As part of their research, Richly and his team have succeeded in connecting the origin of the aging phenotype to a specific tissue, the neurons. If autophagy in the nerve cells of old worms was deactivated, this not only led to an extension of the lifespan, but also to a drastic improvement in the health of the animals. “It's about the same way as if we were taking a medicine halfway through our lives that would help us stay fit, young and live longer. It must be something like this for the worms, ”says Thomas Wilhelm. “We only switch off autophagy in one tissue and there is a change in the entire animal. The neurons in the treated worms are healthier and we believe that this is the reason why the rest of the body and especially the muscles remain healthy. The bottom line is that life is extended by 50 percent. ”

Although the authors do not yet know exactly which mechanism keeps neurons healthy, the results of the study could provide important clues. “There are many neuronal disorders associated with dysfunctional autophagy, such as Alzheimer's, Parkinson's, and Huntington's. It would be possible that the autophagy genes identified in our study open up new therapeutic options, ”said Wilhelm. Although such treatments still seem far away at the moment, the possibility that the new findings can be transferred to humans is promising.

Publication:
Wilhelm T, Byrne J, Medina R, Kolundzic E, Geisinger J, Hajduskova M, Tursun B, and Richly H (2017). Neuronal inhibition of the autophagy nucleation complex extends life span in post-reproductive C. elegans. Genes Dev. 31, (15),
DOI: 10.1101 / gad.301648.117

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