03 December 2015

Thirty Aging Genes

Scientists have identified the genes that determine human aging

Margarita Paimakova, Vesti Having studied about 40 thousand genes of three different organisms, scientists from the Swiss Higher Technical School of Zurich discovered genes involved in the process of physical aging (Peter Rüegg, Genes for a longer, healthier life found).

Moreover, it turned out that if only one of these genes is affected, the healthy life expectancy of laboratory animals increases. Probably, a similar approach will be effective if applied to a person, the researchers conclude.

In search of eternal youth, humanity has been trying for centuries to find an answer to the question of how and why we age. The achievements of recent decades, especially in the field of molecular genetics, have significantly accelerated the search for the genetic basis of the aging process.

Until now, experiments have been limited to individual model organisms, for example, worms nematodes C. elegans. Studies have shown that the lifespan of this creature is affected by about 1% of its genes. However, researchers have long assumed that such genes arose in the process of evolution in all living beings – from yeast to humans.

Scientists from Zurich, together with the JenAge consortium from Jena (Germany), systematized the genomes of three different organisms in search of genes related to the aging process and present in all three species, and thus isolated the gene of a common ancestor.

Despite the fact that such genes (they are called orthologous) are found in different organisms, they are closely related to each other. They are also found in the human body.

To detect these genes, scientists had to study data on 40 thousand nematodes, danio rerio fish and mice. During the screening, scientists sought to determine which of the genes are regulated in the same way in all three organisms during each of the stages of life – youth, maturity and old age (that is, they are either activated or suppressed during aging).

As a parameter determining the activity of genes, the researchers measured the number of mRNA molecules found in the cells of these animals. mRNA transcribes the gene and the production of the corresponding protein.

"If there are many copies of the mRNA of a particular gene in the body, this indicates its high activity. On the contrary, if there are few copies of mRNA, it means that the activity of the gene is low," explains Professor Michael Ristow from the Swiss Higher Technical School of Zurich. – We used statistical models to establish intersections of genes that are regulated in the same way in worms, fish and mice. As it turned out, these three species of living beings have only 30 common genes that significantly affect the aging process."

After conducting experiments in which the mRNAs of the corresponding genes were selectively blocked, scientists accurately determined their effect on the aging process in nematodes. Blocking a dozen genes extended the worms' life by at least 5%.

"One of these genes turned out to be particularly influential: the bcat-1 gene. Turning it off increased the average life expectancy of nematodes by up to 25%," says Ristow (see the graph from the article in Nature Communications – VM).

The researchers also found an explanation for this phenomenon: the bcat-1 gene encodes an enzyme with the same name that reduces the number of so-called branched chain amino acids (L-leucine, L-isoleucine and L-valine).

When the researchers weakened the activity of the bcat-1 gene, branched chain amino acids began to accumulate in the tissues. This process increased not only the lifespan of the worms, but also the length of time during which the creature remains healthy (scientists measured the accumulation of aging pigments, the speed of movement of the nematode, as well as successful reproduction).

The researchers also achieved a life-prolonging effect by adding three branched-chain amino acids to nematode food, but the effect was less pronounced since the gene was still active.

Ristow is sure that the same mechanism is characteristic of the human body.

"We considered only those genes that have been preserved in the process of evolution, so they exist in all living organisms," the scientist notes.

Currently, no such human studies have been conducted (although they are planned). However, scientists believe that measuring the impact of such manipulations on human life expectancy will be problematic for many obvious reasons.

Instead, Ristow and his colleagues plan to focus on the effects of genetic editing on various health parameters, including cholesterol and blood sugar levels.

Scientists have also noticed that several branched chain amino acids are already used for medical purposes (for example, for the treatment of liver damage) and are included in sports nutrition products. However, for a person, the main thing is not to live longer, but to maintain health longer, later to reach an age characterized by chronic diseases. In the future, such studies will help everyone, including the state, to reduce health care costs.

A scientific article by Swiss scientists (Mansfeld et al., Branched-chain amino acid catabolism is a conserved regulator of physiological aging) was published by the journal Nature Communications.

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