Let the neurons rest

Hyperactivity of neurons shortens life

Yulia Vorobyova, Vesti

For the first time, researchers have received evidence that the activity of the nervous system affects life expectancy.

A few years ago, specialists from Harvard Medical School began studying gene expression in the brain tissues of elderly people. The scientists had hundreds of samples obtained from cognitively healthy people who died between the ages of 60 and 100.

The team noticed a curious correlation. The longer a person lived, the less active his genes associated with nervous excitement were (the difference was clearly noticeable in the tissues of people who lived less than 80 and more than 85 years).

But is there a causal relationship? Can the levels of arousal of brain cells directly affect life expectancy? If so, how?

To find answers, scientists conducted many experiments, including genetic, cellular and molecular tests with model roundworms Caenorhabditis elegans, analyses of genetically modified mice and additional analysis of brain tissues of people who have lived for more than a century.

Neuronal activity was much higher in normal worms (orange flashes, left) than in long-lived worms (right). Video: Yankner Lab.

Experiments have shown that the level of neural activity really affects life expectancy. And the key role is assigned to a protein called REST (this abbreviation can be translated as "rest").

Blocking this protein in animals (with the help of drugs or genetic modifications) led to an increase in neural activity and a reduction in life expectancy. And an increase in the production of this protein, on the contrary, suppressed the excitability of brain cells and increased life expectancy (the indicator of worms, for example, was as much as 30%).

Mice that lacked the REST protein (bottom row snapshots) showed much higher neural activity than normal mice (top row snapshots). Photo by Yankner Lab/Nature.

At the same time, it is noted that the decrease in neural activity caused by increased REST expression did not lead to any dysfunctional changes.

"Animals could function, their brains did not "hibernate". However, by suppressing neural activity, it is possible to influence the aging process," explains the senior author of the new study, Professor Bruce Yankner.

Meanwhile, long-lived people were found to have significantly more REST protein in the nuclei of their brain cells than people who died in their 70s or 80s.

"When are brain cells most vulnerable in a person's life? The first time is during fetal development, when the loss of young neurons will lead to very sad consequences. The second is during aging, when you are affected by oxidative stress and improperly folded or aggregated proteins, such as beta-amyloid and tau protein. It is logical that during these two periods, a system of protecting neurons should be included, which for the most part are not restored," says Yankner.

The team also believes that REST, by affecting neural activity in the aging brain, can either increase the likelihood of neurodegeneration, or, conversely, reduce it. In other words, changes in the content of this protein in old age may play a role in the occurrence of senile dementia (dementia) and Alzheimer's disease.

At first glance, the conclusions of the study may seem somewhat illogical (it was even reviewed for two whole years).

So, according to the generally accepted opinion, older people should train the brain, since the effectiveness of thought processes decreases over the years. However, Yankner explains that the kind of excessive neural activity mentioned in his study is not the same as the activity that takes place when performing brain training exercises. In this case, we are talking about hyperexcitability, which is associated with structural degeneration, observed, for example, in Alzheimer's disease.

The authors of the study hope that the findings will open up new ways to develop drugs against aging and neurodegenerative disorders.

However, more research will be needed to believe whether drugs targeting the REST protein, as well as other ways to change neural activity (for example, meditation), can increase people's life expectancy and save their brains from age-related diseases.

More information about the work done is described in an article published in the journal Nature (Zullo et al., Regulation of lifespan by neural excitement and REST).

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