Another potential geroprotector

The results of the work carried out by the staff of the Scripps Research Institute showed that the antidepressant mianserin can increase the duration of the "young adult" phase in roundworms Caenorhabditis elegans, which are a popular model for studying aging.

The work was based on data obtained in 2007, according to which mianserin can increase the life expectancy of roundworms by 40%. According to the head of the study, Michael Petrascheck, the authors wanted to study this issue in more detail and find out how the drug prolongs the life of these organisms.

To do this, they conducted an experiment on 1,000 roundworms that received mianserin or water. Observation of the dynamics of the activity of worms' genes as they age showed unexpected changes in gene expression. The expression of groups of genes performing similar functions changed in opposite directions. For example, the expression of some of the genes regulating metabolism increased, while the expression of other genes in this group, on the contrary, decreased.

The most interesting thing turned out to be that these shifts were tracked with high accuracy as the worms matured, which provided scientists with a new method for predicting the life expectancy of an individual, giving reliable results even if the individual has not yet emerged from "adolescence".

The authors called this phenomenon a "transcriptional shift". The study of data on gene expression in mice and 32 people aged 26 to 106 years allowed them to conclude that the revealed phenomenon extends to mammals.

Instead of tracking aging by waiting for the death of an organism, researchers can now track the transcriptional shift, which allows us to identify the age of the organism at which age-related transcription changes begin to appear.

The use of this new tool has shown that mianserin therapy is able to suppress the transcriptional shift, but only when used at an early age. The onset of mianserin exposure on the first day of life increased the lifespan of worms by 7-8 days, the average value of which under normal conditions is 21 days.

At the same time, transcriptional shift tracking showed that therapy selectively increased the duration of the period corresponding to young adulthood. In fact, the transcriptional shift of the 10-day-old worms exposed to the drug corresponded to the transcriptional shift of the 3-day-old worms of the control group, that is, the period of young adult age in them was increased by more than 3 times.

Subsequent experiments have shown that mianserin can only suspend the aging process, and not reverse it. Its effect on worms, started at 3 days of age, provided only a slight increase in life expectancy, whereas the effect on the fifth day of life had no effect.

The data obtained by the authors indicate that mianserin blocks signals associated with serotonin regulation, which delays the manifestation of age-related physiological changes, including transcriptional shift and degenerative processes leading to the death of the body.

The next stage of the work will be to reproduce the results obtained in mice and identify possible side effects of mianserin therapy.

The authors emphasize that they do not want people to get the impression that the drug under study can be used to prolong youth. The results obtained are relevant for roundworms, and millions of years of evolution lie between them and humans.

Article by Sunitha Rangaraju et al. Suppression of transcriptional drift extends C. elegans lifespan by postponing the onset of mortality is published in the journal eLife.

Evgeniya Ryabtseva

Portal "Eternal youth" http://vechnayamolodost.ru Based on Scripps Research Institute: TSRI Scientists Prolong 'Young Adult' State in Worms.