The Grapevine

Can Excessive Brain Activity Lead To Earlier Death?

Overactive neural activity might lead to faster aging and reduce human lifespan, according to the latest research by Blavatnik Institute at Harvard Medical School, published on October 16 in the journal Nature. Suppressing a highly stimulated brain could add more years to the lives of the elderly, they found. 

This study is said to be the first one to analyze the link between neural activity and lifespan in human beings. In the past, some studies have pointed out that the aging process in animals is affected by certain functions of the nervous system. However, hyperactive neural function has not been studied before in both humans and animals. 

"An intriguing aspect of our findings is that something as transient as the activity state of neural circuits could have such far-ranging consequences for physiology and life span," Bruce Yankner, study senior author and professor of genetics at HMS, said. 

The Study

Harvard scientists took brain tissue samples of more than a hundred dead elderly people without dementia, who had donated their brains for medical research from three different studies.The purpose was to analyze the gene expression patterns of the protein called REST that can regulate neural excitation. REST has been linked to the development of Alzheimer's before, but its association with reducing mortality is new. 

A comparison was made between the brains of people who died before their mid-80s to those who lived up to a 100 and beyond. Major differences were observed between the two categories of participants. The study found that people who had passed away at 60 to 80 years old had higher gene expression that caused neural excitation than the centenarians.

Brain Scan A picture of a human brain taken by a positron emission tomography scanner, also called PET scan, is seen on a screen on January 9, 2019, at the Regional and University Hospital Center of Brest, western France. Fred Tanneau/AFP/Getty Images

Furthermore, the researchers had to determine if other factors had played a role along with faulty gene expression or whether it was the singular cause. The team tested genetic, cell and molecular biology aspects of more brain tissue samples of people, mice genetically altered to not possess REST and another model organism called Caenorhabditis elegans to be doubly sure. 

"It was extremely exciting to see how all these different lines of evidence converged," Monica Colaiácovo, co-author and professor of genetics at Harvard Medical School, said. Moreover, the research revealed that neural excitation does seem to have an impact on the longevity of a person's life on a molecular level.  

New Therapies  

Blocking REST in animals, such as worms or mammals, increased excitable brain activity and shortened their life span. When the production of REST was stimulated, the opposite effect was noticed. Also, looking at the brains of deceased 100-year-olds, the nuclei in their brain cells showed much higher evidence of the protein. REST travels through ion channels, synapses and neurotransmitters all over the body and is centrally involved in the process of increasing or decreasing neural excitation.

The study now motivated researchers to develop drugs to target the REST protein and boost its production to decrease mortality rates in human beings. Although further tests and more experiments are needed, the concept caught the imagination of a few scientists. "The possibility that being able to activate REST would reduce excitatory neural activity and slow aging in humans is extremely exciting," Colaiácovo added.