Brain activity linked to longevity

Is it possible to think too much? New research has revealed some startling findings, with too much thinking linked to a shorter life span.

The brain’s neural activity, long implicated in disorders ranging from dementia to epilepsy, plays a role in human ageing and life span, according to scientists from the Harvard Medical School.

The study is based on findings from human brains, mice and worms and suggests that excessive activity in the brain is linked to shorter life spans, while suppressing such overactivity extends life.

The findings offer the first evidence that the activity of the nervous system affects human longevity. Although previous studies had suggested that parts of the nervous system influenced ageing in animals, the role of neural activity in ageing, especially in humans, remained murky.

“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,” said study senior author Professor Bruce Yankner.

Neural excitation appears to act along a chain of molecular events famously known to influence longevity: the insulin and insulin-like growth factor (IGF) signalling pathway.

The key in this signalling cascade appears to be a protein called REST, previously shown by the Yankner Lab to protect ageing brains from dementia and other stresses.

Neural activity refers to the constant flicker of electrical currents and transmissions in the brain. Excessive activity, or excitation, could manifest itself in numerous ways, from a muscle twitch to a change in mood or thought, the authors said.

It’s not yet clear from the study whether or how a person’s thoughts, personality or behaviour affect their longevity.

“An exciting future area of research will be to determine how these findings relate to such higher-order human brain functions,” said Prof. Yankner.

The study could inform the design of new therapies for conditions that involve neural overactivity, such as Alzheimer’s disease and bipolar disorder, the researchers claim.

The findings raise the possibility that certain medicines, such as drugs that target REST, or certain behaviours, such as meditation, could extend life span by modulating neural activity.

Human variation in neural activity might have both genetic and environmental causes, which would open future avenues for therapeutic intervention, Prof. Yankner said.

The study analysed gene expression patterns – the extent to which various genes are turned on and off – in donated brain tissue from hundreds of people who died at ages ranging from 60 to over 100.

The information had been collected through three separate research studies of older adults. Those analysed in the current study were cognitively intact, meaning they had no dementia.

Immediately, a striking difference appeared between the older and younger study participants, said Prof. Yankner. The longest-lived people – those over 85 – had lower expression of genes related to neural excitation than those who died between the ages of 60 and 80.

The team then tested genetically-altered mice and additional brain tissue analysis of people who lived for more than a century.

These experiments revealed that altering neural excitation does indeed affect life span – and illuminated what might be happening on a molecular level.

All signs pointed to the protein REST.

REST, which is known to regulate genes, also suppresses neural excitation, the researchers found.

Blocking REST or its equivalent in the animal models led to higher neural activity and earlier deaths, while boosting REST did the opposite. And human centenarians had significantly more REST in the nuclei of their brain cells than people who died in their 70s or 80s.

In addition to its emerging role in staving off neurodegeneration, discovery of REST’s role in longevity provides additional motivation to develop drugs that target the protein.

Although it will take time and many tests to determine whether such treatments reduce neural excitation, promote healthy ageing or extend life span, the concept has captivated some researchers.

What do you think about this research? Do you think an overactive brain leads to a shorter life? Does this research support commonly held views about the benefits of meditation?

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