Edge of Innovation

Forever young: Researchers discover genes that influence lifespan

Do genes influence our lifespan? If so, which ones? These questions were posed by researchers from ETH Zurich in Switzerland and the research consortium “JenAge”—based in Jena, Germany—as part of a joint study. The scientists were able to identify 30 genes that have a significant impact on the aging process by studying around 40,000 genes from mice, zebrafish and the roundworm C. elegans. To find out which of these genes have an influence on the aging process across all three species, the quantity of a substance known as messenger ribonucleic acid (mRNA) in the animals’ cells was measured. The number of these single-strand RNA transcripts can indicate whether a gene is particularly active or not.

Throughout the stages of an organism’s life, genes can change their levels of activity — a process known as upregulation or downregulation in scientific terms. ETH professor Michael Ristow and his team of researchers used this fact to search for genes that are regulated in exactly the same way across all three organisms in the respective life stages of juvenile, adult and old-aged. As a result, it was possible to conclude that such genes are connected to the aging process. At the end of the study, all three species only had 30 “aging genes” in common out of the thousands of genes investigated.

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A longer and more energetic life

Lifespan increased by 25 percent on average

Among these 30 genes, the Bcat-1 gene was identified as being particularly influential. When this gene was downregulated in roundworms, the animal’s lifespan increased by 25 percent on average. “This is the most significant effect on lifespan that we have been able to measure in our trials,” explains Professor Michael Ristow. Furthermore, the worm—which only lives for 14 to 20 days on average—remained vital for longer. This improvement was visible in parameters such as age-related pigments, speed of movement and frequency of reproduction. According to Ristow, all of these factors had improved.

The scientists have identified so-called branched-chain amino acids as the reason behind the increased vitality and life expectancy. As Bcat-1 contains the blueprint for an enzyme that causes these amino acids to decay, greater levels of the amino acids accumulate in the animal’s body when the gene is blocked. As a comparison, the effects were also studied when the animals were given feed enriched with the amino acids. In this instance, a positive effect on lifespan and health was again found, but the effect was less pronounced.

Effects in humans also possible

The mechanism works in a similar way in humans

The present study completely excludes the impact on humans. However, on the basis of the results, the researchers are already convinced that this mechanism works in a similar way in our bodies. “We have only searched for those genes that are evolutionarily conserved and that therefore occur in all organisms, including humans,” said Ristow, an expert in energy metabolism and coordinating author of the study.

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According to the ETH professor, the follow-up study is already in the planning stage. However, Ristow states that—for obvious reasons—this study could not be used to measure the life expectancy of humans, because that would significantly exceed the duration and budget of a research project. Instead, parameters such as cholesterol and blood sugar levels would be examined as meaningful indicators of the test subjects’ state of health.

Not older, but healthier

The goal is not to increase life expectancy

According to Ristow, numerous branched-chain amino acids are already used therapeutically, for example to treat liver damage or for sports nutrition. The goal of the research is not to further increase the already rising life expectancy of humans, explains the scientist. In view of demographic developments and the cost of medical care, Ristow believes that it does not make sense to aim for an even higher life expectancy plagued by illnesses.

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On the contrary, the intention is to prolong the healthy and vital phase of life. Studies like this can offer important insights into the aging process and significantly contribute to preventing chronic age-related diseases, such as diabetes or high blood pressure. Ristow emphasizes that such achievements not only improve the quality of life of older people — they also make it possible to reduce medical and healthcare costs considerably.

DNACover photo: Flickr — Mehmet Pinarci (CC BY 2.0)Image 1: Wikipedia — Dan Dickinson (CC BY-SA 3.0)Gif 1: Flickr — Vancouver Film School (CC BY 2.0)Gif 2: Imgur — orbojunglist

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