German scientists reveal great secret of eternal youth

What makes us age? - The secret of youth
Researchers at the Institute of Molecular Biology (IMB) in Mainz have achieved a breakthrough in research into the aging process. The scientists were able to prove that genetic factors can slow down aging. However, these factors cause the process to accelerate as people get older.

In the roundworm of the species Caenorhabditis elegans have Dr. med. Holger Richly and his colleagues discovered genetic factors that slow down aging in young animals, but speed it up in later life. Astonishingly, the identified genes control the intracellular process of autophagy, which degrades nonfunctional cell constituents and is generally attributed to health promoting properties. The research findings were recently published in the scientific journal "Genes & Development" and provide first indications of how the aging process has emerged as an inevitable byproduct of evolution.

Forever Young. This is an old human dream. Scientists are on the track. (Image: Dan Race / fotolia.com)

In their publication, the scientists show that lifespan is prolonged when the autophagy process is downregulated in older animals, leading to maintenance of healthy nerve cells and, more generally, to improved health. These new findings may also have implications for the treatment of neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's, in which the autophagy process also plays a role.

Every human and almost every species on our planet is aging. The question is: why? According to Charles Darwin's theory of evolution, natural selection means that living organisms that adapt optimally to one habitat have a greater chance of surviving and passing their genes on to subsequent generations. The more successful the properties of certain genes support the propagation, the more is selected for these genes. On this basis, George C. Williams developed in 1957 antagonistic pleiotropy (AP) an aging hypothesis that states that evolution selects genes that are beneficial in the youth and reproductive period, but have negative effects in old age. Although this theory is mathematically substantiated, so far there has been little experimental evidence that genes behave according to this hypothesis.

In her now available publication "Neuronal inhibition of the autophagic nucleation complex extends lifespan in post-reproductive C. elegans". Holger Richly and his laboratory at the IMB in Mainz have shown that many genes show an AP behavior and thus greatly accelerate the aging process. Although the team of researchers studied only a fraction of the genome of Caenorhabditis elegans with 800 out of approximately 20,000 genes, the scientists were able to find a considerable number of 30 genes that behave according to AP theory. "Considering that we only tested four percent of the worm's genes on our screen, it's likely that many other AP genes can be identified," said Jonathan Byrne, a former Ph.D. Holger Richly at IMB and one of the two main authors of the study.

"The proof that aging is driven by evolution was not the only surprise in our research," adds Thomas Wilhelm, co-lead author of the publication. "What surprised us most was recognizing the fundamental biological processes involved in the identified genes." The scientists found that autophagy, which is an essential cellular recycling process, is normally needed to maintain life and longevity , shows a very strong AP behavior. "At this point, our research was really fascinating," Dr. Holger Richly, Research Group Leader at IMB and Project Leader of this study. It is well known that the autophagy process gets worse and worse with age, but the authors of the study show that it is completely dysfunctional and even harmful in older worms. Molecular biologists have shown that downregulating key genes that initiate the autophagy process dramatically increases lifespan.

"These findings should make us think and lead us to critique our theories of autophagy," Dr. Holger Richly explains, "Autophagy has almost always been considered beneficial, even if it hardly works. In contrast, we show the serious, negative consequences that can occur when autophagy gradually collapses late in life, and that it would probably be better to bypass autophagy in old age. This is classic antagonistic pleiotropy: in young worms, autophagy works well and is essential to the development of the animal, but after reproduction it becomes defective and causes the animals to age. "

As part of her research, Richly and his team have succeeded in linking the origin of the aging phenotype to a specific tissue called neurons. Deactivating autophagy in the neurons of old worms not only prolongs lifespan, but also dramatically improves animal health. "It's kind of like we're taking a medicine halfway through our lives that helps us stay fit and young and live longer. It must be something like that for the worms, "says Thomas Wilhelm. "We turn off autophagy only 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 that the rest of the body and especially the muscles stay healthy. The bottom line is that it leads to a life extension of 50 percent. "

Although the authors do not yet know exactly which mechanism keeps the 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 for the autophagy genes identified in our study to open up new therapeutic options, "says Wilhelm. Although such treatments are still a long way off, the possibility of the new findings being 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 autophagy nucleation complex extends life span in post-reproductive C. elegans. Genes Dev. 31, (15),
DOI: 10.1101 / gad.301648.117