Thinking about death: High neural activity is linked to shorter lifespans

After a comprehensive study, researchers came to a startling conclusion.

The Thinker
Flickr user Todd Martin
  • Researchers have discovered that higher levels of neural activity cause shorter lifespans, with evidence drawn from studies on roundworms, mice, and humans.
  • A protein called REST appears to be a key player; REST regulates the expression of several genes, many of which affect neural activity.
  • The findings offer new targets for further studies on longevity and may even lead to the development of a longevity drug.


If there's one thing that humans can't stop thinking about, it's death. But new research published in the journal Nature suggests that all that thinking might be the very thing that brings death on.

More precisely, researchers discovered that higher neural activity has a negative effect on longevity. Neural activity refers to the constant flow of electricity and signals throughout the brain, and excessive activity could be expressed in many ways; a sudden change in mood, a facial twitch, and so on.

"An exciting future area of research will be to determine how these findings relate to such higher-order human brain functions," said professor of genetics and study co-author Bruce Yankner. While it's probably not the case that thinking a thought reduces your lifespan in the same way smoking a cigarette does, the study didn't determine whether actual thinking had an impact on lifespan — just neural activity in general.

The role of REST

To say this was an unexpected finding is an understatement. We expect that aging affects the brain, of course, but not that the brain affects aging. These results were so counterintuitive that the study took two additional years before it was published as the researchers gathered more data to convince their reviewers. Yankner was forbearing about the delay. "If you have a cat in your backyard, people believe you," he said. "If you say you have a zebra, they want more evidence."

Yankner and colleagues studied the nervous systems of a range of animals, including humans, mice, and Caenorhabditis elegans, or roundworm. What they found was that a protein called REST was the culprit behind high neural activity and faster aging.

First, they studied brain samples donated from deceased individuals aged between 60 and 100. Those that had lived longer — specifically individuals who were 85 and up — had unique gene expression profile in their brain cells. Genes related to neural excitation appeared to be underexpressed in these individuals. There was also significantly more REST protein in these cells, which made sense: REST's job is to regulate the expression of various genes, and it's also been shown to protect aging brains from diseases like dementia.

But in order to show that this wasn't simply a coincidence, Yankner and colleagues amplified the REST gene in roundworm and mice. With more REST came quieter nervous systems, and with quieter nervous systems came longer lifespans in both animal models.

A path to longevity

Neural activity in mice

Normal mice (top) had much lower levels of neural activity than mice lacking the REST protein (bottom). Neural activity is color coded, with red indicating higher levels.

Zullo et al., 2019

Higher levels of REST proteins appeared to activate a chain reaction that ultimately led to these increases in longevity. Specifically, REST suppressed the expression of genes that control for a variety of neural features related to excitation, like neurotransmitter receptors and the structure of synapses. The lower levels of activity activated a group of proteins known as forkhead transcription factors, which play a role in regulating the flow of genetic information in our cells. These transcription factors, in turn, affect a "longevity pathway" connected to signaling by the hormones insulin and insulin-like growth factor 1 (IGF1).

This longevity pathway has been identified by researchers before, often in connection with possible benefits to lifespan from fasting. Additionally, the insulin/IGF1 hormones are critical for cell metabolism and growth, features which relate to longevity in obvious ways.

The most exciting aspect of this research is that it offers targets for future research on longevity, possibly even allowing for the development of a longevity drug. For instance, anticonvulsant drugs work by suppressing the excessive neural firing that occurs during seizures, and in studies conducted on roundworms, they've also been shown to increase lifespan. This recent study shows that this connection might not be coincidental. Similarly, antidepressants that block serotonin activity have also been shown to increase lifespan. Dietary restriction has long been implicated in promoting longer lifespans as well. Dietary restriction lowers insulin/IGF1 signaling, which this study showed affects the REST protein and neural activity. More research will be needed to confirm or reject any of these possibilities, but all represent exciting new avenues to explore, possibly resulting in the extension of our lifespans.

COVID-19 amplified America’s devastating health gap. Can we bridge it?

The COVID-19 pandemic is making health disparities in the United States crystal clear. It is a clarion call for health care systems to double their efforts in vulnerable communities.

Willie Mae Daniels makes melted cheese sandwiches with her granddaughter, Karyah Davis, 6, after being laid off from her job as a food service cashier at the University of Miami on March 17, 2020.

Credit: Joe Raedle/Getty Images
Sponsored by Northwell Health
  • The COVID-19 pandemic has exacerbated America's health disparities, widening the divide between the haves and have nots.
  • Studies show disparities in wealth, race, and online access have disproportionately harmed underserved U.S. communities during the pandemic.
  • To begin curing this social aliment, health systems like Northwell Health are establishing relationships of trust in these communities so that the post-COVID world looks different than the pre-COVID one.
Keep reading Show less

The "singleton hypothesis" predicts the future of humanity

Philosopher Nick Bostrom's "singleton hypothesis" predicts the future of human societies.

Politics & Current Affairs
  • Nick Bostrom's "singleton hypothesis" says that intelligent life on Earth will eventually form a "singleton".
  • The "singleton" could be a single government or an artificial intelligence that runs everything.
  • Whether the singleton will be positive or negative depends on numerous factors and is not certain.
Keep reading Show less

What the Greek classics tell us about grief and the importance of mourning the dead

The rites we give to the dead help us understand what it takes to go on living.

Photo by Stavrialena Gontzou on Unsplash
Culture & Religion

As the coronavirus pandemic hit New York in March, the death toll quickly went up with few chances for families and communities to perform traditional rites for their loved ones.

Keep reading Show less

Bruce Lee: How to live successfully in a world with no rules

Shannon Lee shares lessons from her father in her new book, "Be Water, My Friend: The Teachings of Bruce Lee."

Bruce Lee: How to live successfully in a world with no rules ...
Videos
  • Bruce Lee would have turned 80 years old on November 27, 2020. The legendary actor and martial artist's daughter, Shannon Lee, shares some of his wisdom and his philosophy on self help in a new book titled "Be Water, My Friend: The Teachings of Bruce Lee."
  • In this video, Shannon shares a story of the fight that led to her father beginning a deeper philosophical journey, and how that informed his unique expression of martial arts called Jeet Kune Do.
  • One lesson passed down from Bruce Lee was his use and placement of physical symbols as a way to help "cement for yourself this new way of being, or this new lesson you've learned." By working on ourselves (with the right tools), we can develop the skills necessary to rise and conquer new challenges.
Keep reading Show less
Scroll down to load more…
Quantcast