First time Scientists identify the role of neuronal activity in human longevity

A recent study offers the very first evidence that the activity of the nervous system affects human longevity. Neuronal excitation appears to act along a chain of molecular events known to influence longevity.

In fact, according to a new study conducted by scientists at Harvard Medical School's Blavatnik Institute (HMS), neuronal activity in the brain (long implicated in disorders ranging from dementia to epilepsy) also plays a role. key role in human aging and the lifespan of a human being.

This new study is based on discoveries about the human brain (as well as that of mice), and suggests that excessive activity in the brain is linked to a shorter life span, while suppressing this overactivity increases longevity of a human being.

The results of this new study offer the very first evidence that the activity of the nervous system affects human longevity. Although previous studies have suggested that some parts of the nervous system affect aging in animals, the role of neuronal activity in aging, particularly in humans, remained unclear.

" An intriguing aspect of our findings is that such a transient element of neuronal circuit activity can have such significant physiological and life-span consequences ," said the lead author of the study. 'study, Bruce Yankner, professor of genetics at the HMS and co-director of the Paul F. Glenn Center for the Biology of Aging.

According to the results of the researchers, neuronal excitation seems to act along a chain of molecular events known to influence longevity: the signaling pathway of insulin and insulin-like growth factor (so-called IGF).

The key to this true signaling cascade appears to be a protein called REST , previously presented by Yankner Lab as capable of protecting aging brains from dementia and other stressors. Indeed, this neuronal activity refers to the constant flicker of electrical currents and transmissions in the brain. And according to the authors, such excessive activity could manifest in many ways, ranging from muscle contractions to a change of mood, or even thought.

The new study does not yet specify whether, and how, thoughts, personality or behavior of a person can affect the longevity of the individual. " A future exciting area of ​​research will be to determine the link between these findings and the higher brain functions of such an order, " Yankner said.

In any case, according to the researchers, these discoveries (from this study) may well help in the design of new treatments for diseases involving neuronal overactivity, such as Alzheimer's disease and bipolar disorder.

In addition, the results raise the possibility that certain drugs, such as rest-medications, or certain behaviors (such as meditation), may prolong life by modulating neuronal activity.

Indeed, the variant of human behavior with respect to neuronal activity " could have both genetic and environmental causes, which would open up new avenues for therapeutic intervention,  " said Yankner.

Yankner and his colleagues began their research by analyzing patterns of gene expression: the extent to which various genes are turned on and off, in brain tissue from hundreds of deceased people (at ages 60 to over 100 years).

This information was collected in three separate studies of older people. The data analyzed in this study were all cognitively intact, meaning that they did not suffer from dementia. " Older people - those over 85 years of age - had lower neural excitation gene expression than those who died between the ages of 60 and 80 ," Yankner said.

Then, scientists wondered if this was an effect of correlation or causality. Indeed, did this disparity in neuronal excitation simply occur because of larger factors, determining life span, or did the levels of excitation directly affect longevity? And if so, how?

The team conducted a series of experiments, including genetics, cell and molecular biology, in the model organism, Caenorhabditis elegans (a small, transparent, non-parasitic worm), and genetically modified mice. Additional brain tissue analyzes of people who have lived more than a century have also been performed.

The results revealed that the modification of neural excitation actually affected the lifespan and made it possible to highlight what could happen at the molecular level.

Mice lacking the REST protein (bottom) demonstrated much higher neuronal activity in the brain (in red) than normal mice (top). Credits: Yankner Lab / Nature

All the elements pointed to the protein mentioned above, known as REST: the researchers discovered that this protein, also known to regulate genes, also inhibited neuronal excitation. Indeed, the blocking of the REST protein, or its equivalent in animal models, resulted in higher neuronal activity and earlier deaths, whereas the reinforcement of the REST protein had the opposite effect. In addition, scientists found that human centenarians had significantly more REST protein in the nuclei of their brain cells than people who died between the ages of 70 and 80 years.

In addition, researchers have found that, from worms to mammals, REST protein literally suppresses the expression of genes that play a central role in neuronal excitation, such as ion channels, neurotransmitter receptors, and structural components of neurons. synapses. " It was extremely exciting to see how all these data sources converged,  " said Monica Colaiácovo, co-author of the study and professor of genetics at the HMS.

It should also be noted that a weaker excitation in turn activates a family of proteins known as FOX (Forkhead box). These proteins have been shown to induce a longevity pathway via insulin / IGF signaling in many animals. Scientists believe that this path could also be activated by caloric restriction.

In addition to its emerging role in the fight against neurodegeneration, the discovery of the role of REST protein in the field of human longevity, provides additional motivation to develop drugs that target the latter.

Of course, more time, more research, and many more tests will be needed to determine whether such treatments could actually reduce neuronal excitation and promote healthy aging (or prolonging life).

But in any case, this concept fascinates many researchers in the field: " The possibility that activating REST protein reduces excitatory neuronal activity and slows down aging in humans is extremely fascinating ! "Said Colaiácovo.


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