Stop aging

Ekaterina Borovikova, "The Attic"Some animals manage not to grow old; by examining them, it may be possible to rid a person of this scourge.

Most animals, including humans, unfortunately, are aging. But scientists who study the mechanisms that allow to increase life expectancy believe that one day they will be able to save us from the "inevitable".

Aging – at least in part – occurs due to the fact that the functioning of the regulatory networks that control the activity of genes in cells is disrupted. The "misregulation" of the genes leads to the development of various diseases, senility and, ultimately, death.

In order to find out which parameters affect the stability of regulatory networks, Peter Fedichev from the Moscow Institute of Physics and Technology and the biotechnology company Gero and his colleagues created a physical model of aging using critical dynamics research methods - this section of statistical physics describes the properties of a physical system at or near a critical point. The results of this work are published in the journal Scientific Reports: Kogan et al., Stability analysis of a model gene network links aging, stress resistance, and negligible senescence (the press release Physics meets biology to defeat aging can be read on the EurekAlert - VM website).

"We have shown that the stability of the gene network is determined by several parameters, such as the connectivity of the gene network (the number of signaling pathways and similar mechanisms that ensure the interaction of network elements – genes, proteins, etc. – with each other), the "effective" size of the genome (the number of active genes from which RNA is synthesized and then proteins are formed), the rate of updating or correcting errors in the proteome (a set of proteins produced by the cells of the body), the rate of DNA repair, and others. By changing each of these parameters, it is possible to regulate the life span of a living organism," Fedichev explained to The Attic.

There are examples of changes in these parameters in living organisms during evolution or in laboratory experiments. Thus, less connectivity of the gene network contributes to a longer life span. An example of its reduction is the transfer of mitochondrial genes to the nuclear genome. It is believed that this is one of the main factors that led to the formation of multicellular organisms, their sharp complication and an increase in their life expectancy.

Mitochondria are organelles in a cell that produce energy that supports cellular processes. Scientists believe that they appeared millions of years ago, when the unicellular ancestors of modern animals "captured" free-living bacteria and they established a symbiotic relationship. As a result, there were two sets of DNA in one cell: nuclear and mitochondrial. However, in modern animals, most of the mitochondrial genes have "moved" into nuclear DNA and the main proteins necessary for mitochondria to work are produced in the cytoplasm of the cell and go to the mitochondria from there.

Due to the fact that part of the mitochondrial genome has become part of the nuclear one, they have a common mechanism of regulation and there is no need to build additional "connections" between them, as it was before. Thus, the connectivity of the gene network has decreased.

Now scientists are conducting experiments to prolong life by artificially reducing the connectivity of the gene network. So, it turned out that disabling certain intracellular signaling pathways in nematode worms leads to an increase in their life expectancy by 10 times.

Another example is the increase in the resistance of the genetic network to breakage in naked diggers. They are faster than other rodents, DNA is "repaired" in case of damage and the proteome is updated. Thanks to this, naked diggers live 10 times longer than other rodents and do not get cancer. Experiments to increase the rate of proteome renewal were carried out on yeast, and, as in the case of nematodes, allowed to increase the lifespan of organisms.

Fedichev believes that in the future these methods can be applied to humans. "If this happens, slowing down aging will increase the duration of a healthy human life, postpone the occurrence of age-related diseases, including cancer in adults, many cardiovascular diseases, Alzheimer's disease, etc.," the scientist explained.

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15.09.2015