Nature: new research reveals for the first time that inhibition of age-related neural activity increases life expectancy

October 20, 2019 / Biovalley BIOON / - -- in a study of nematodes, mice and humans, researchers from Harvard Medical School in the United States found that aging brings more neural activity throughout the animal kingdom, and when this natural increase is limited, an individual's life span may be longer They highlighted a conserved transcription factor called rest, which may be key to regulating this age-related neural activity The relevant research results are published in the nature Journal on October 17, 2019, and the paper title is "regulation of lifespan by natural exception and rest" Picture from nature, 2019, DOI: 10.1038/s41586-019-1647-8 "This is a very interesting paper that provides us with food for the mind," said Shin Ichiro Imai, a developmental biologist at Washington University's St Louis School of medicine Joy Alcedo, who studies nematode and fruit fly aging at Wayne State University in the United States (who was not involved in the study), added, "this is a fascinating idea: as people age, our neurons may actually become more active, and simply suppressing this neural activity may be enough to prolong life." Bruce yankner, a neuroscientist and geneticist at Harvard Medical School and the corresponding author of the paper, said that as people grow older, gene expression patterns in the brain change in a non random way, so that young people and old people can be distinguished by their transcriptional characteristics Of course, all the old people are different Some are healthy, some are not so healthy Yankner and his colleagues are interested in whether certain expressive features are related to this difference Instead of dividing the elderly into specific groups based on health, longevity or any other parameters, the researchers asked the data to help them They obtained RNA from the frontal cortex of hundreds of deceased elderly subjects and sequenced it through a computational process called unsupervised hierarchical clustering In this process, the computer iteratively determines who is closest to whom The result, he said, is that the RNA transcripts "spontaneously divide into people younger than 80 and people older than 85 or 90, and this distribution can be observed in three different cohorts, so it has good repeatability." By studying the differences in key gene expression between the two groups, the researchers found that people who lived longer had fewer transcripts of genes involved in nerve excitation and synaptic function than those who died earlier To get their research beyond this interesting correlation, the researchers turned to animal models Yankner explained that Caenorhabditis elegans is a very convenient organism for studying aging, because "they only live for about three weeks." His team found that neurons in older nematodes tended to discharge faster than those in younger ones, but in mutant nematodes with significantly longer lifespans, neuronal activity "remained almost silent." "This is the softest nematode you can imagine." In addition, the use of drugs that inhibit neural activity can increase the life span of wild-type nematodes Li Huei Tsai, a neuroscientist at the Massachusetts Institute of Technology who was not involved in the study, said: "I personally think this is a very surprising result When you think about longevity, it's very mysterious You might think it could involve many different things But please note that [the researchers] adjust only one thing, which is enough to change life expectancy " The use of genetic tools to shut down excitatory or inhibitory neurons in nematodes results in longer or shorter life expectancy, respectively, just as they increase or inhibit the level of a transcription factor called spr-4 Spr-4 is a mammalian transcription factor rest homologue in nematodes, in which rest is a transcription repressor that shuts down neural genes Importantly, in human subjects, people who lived to be 100 or older had significantly higher levels of rest protein than those who died between the ages of 70 and 80 Moreover, brain scans showed a global increase in neural activity in genetically engineered mice lacking rest However, the effect of rest on the life span of mice has not been studied "If these authors were able to find ways to extend the lifespan of mice by increasing their levels of rest in the brain, then this would be closer to humans than nematode research," Imai said However, as he points out, life tests on mice that can survive two or three years are much more difficult than in nematodes If such a result can be confirmed and its mechanism understood, Imai said, it will open the door for potential manipulation of the system, and "anti-aging interventions may become a reality in the near future." (bio Com) reference: 1 Joseph M Zullo et al Regulation of lifespan by natural exception and rest Nature, 2019, DOI: 10.1038/s41586-019-1647-8 2 Incremental national activity shortcuts lifespan in animals https://www.the-scientist.com/news-opinion/increased-national-activity-shortcuts-lifespan-in-animals-66577