Brain activity linked to longevity


Long-lived individuals have less excitable neurons. Paul Biegler reports.


Less excitable neurons could lead to a longer life. 

Andrew Brookes

A team led by genetics researchers from Harvard Medical School has discovered that a protein named REST helps you live longer by damping down activity in the brain.

The finding, published in the journal Nature, shows for the first time how the brain regulates ageing and could herald new treatments for age-related diseases such as Alzheimer’s.

The researchers, led by Bruce Yankner from the Department of Genetics at Harvard Medical School in Boston, US, examined hundreds of post mortem brain specimens from three separate studies of older people who were free of dementia.

When they compared the brains of people over 85 to those of people who died younger - between 65 and 80 - they found something curious; in those older brains the genes that fire up brain cell activity were turned right down.

Something was dialling down neural activity in the longer-lived bunch and Yankner’s team had a prime suspect.

It was a protein called REST.

REST has a reputation as an all-purpose brain protectant. It defends neurons against oxidative stress, an all-of-body inflammatory response triggered by things such as smoking, obesity, and pollution. It can also fend off the amyloid that forms brain plaques in Alzheimer’s.

But REST is also known as a general suppressor of neural activity. And, it turned out, the protein was working overtime in those folk with the extra miles on the clock.

When it comes to neurons, it seems, it is REST by name and “rest” by nature.

The big question, of course, is whether quieter neurons are simply a concomitant of ageing or whether they are prime movers of an extended lifespan.

To find out, the team turned to the humble roundworm Caenorhabditis elegans, which has put its body on the line repeatedly for science - most recently as the first ever organism to have its entire nervous system mapped.

This time C. Elegans was in for some drug testing.

First up the worm was given a drug that turned down its nerve cell activity. It lived longer. Then it was given a genetic tweak that fired up its nerve cells. It died younger (whether it stayed pretty was not reported).

The results were well and truly in – it looks like neural activity really is a regulator of the lifespan.

Equally intriguing is another link the researchers found in that longevity chain.

In separate experiments with the worm’s own version of REST they found the same effect on lifespan; increased REST made for longer-lived worms, and vice versa.

That effect, the authors discovered, was mediated by insulin, the hormone that pushes sugar into cells, and a related peptide called Insulin-like growth factor 1 (IGF-1).

As it happens, insulin and IGF-1 are possible signals by which calorie restriction helps humans live longer.

“It was extremely exciting to see how all these different lines of evidence converged,” says Monica Colaiácovo, a co-author on the study from Harvard.

The researchers say their discovery could inform new therapies for Alzheimer’s disease and bipolar disorder – overactive brain cells are a feature in both illnesses.

As aspirations go, however, the fountain of youth is always hard to beat.

“The possibility that being able to activate REST would reduce excitatory neural activity and slow ageing in humans is extremely exciting,” says Colaiácovo.

Contribs paulbiegler 2.jpg?ixlib=rails 2.1
Paul Biegler is a philosopher, physician and Adjunct Research Fellow in Bioethics at Monash University. He received the 2012 Australasian Association of Philosophy Media Prize and his book The Ethical Treatment of Depression (MIT Press 2011) won the Australian Museum Eureka Prize for Research in Ethics.
  1. https://www.nature.com/articles/s41586-019-1647-8
  2. https://www.nature.com/articles/nature13163
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568826/
  4. https://www.ncbi.nlm.nih.gov/pubmed/24149584
  5. https://cosmosmagazine.com/biology/the-wiring-of-worms-revealed
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367275/
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