Thinking about death: High neural activity is linked to shorter lifespans
After a comprehensive study, researchers came to a startling conclusion.
- 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
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.
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.
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The idea of 'absolute time' is an illusion. Physics and subjective experience reveal why.
- Since Einstein posited his theory of general relativity, we've understood that gravity has the power to warp space and time.
- This "time dilation" effect occurs even at small levels.
- Outside of physics, we experience distortions in how we perceive time — sometimes to a startling extent.
Physics without time<p>In his book "The Order of Time," Italian theoretical physicist Carlo Rovelli suggests that our perception of time — our sense that time is forever flowing forward — could be a highly subjective projection. After all, when you look at reality on the smallest scale (using equations of quantum gravity, at least), time vanishes.</p><p style="margin-left: 20px;">"If I observe the microscopic state of things," writes Rovelli, "then the difference between past and future vanishes … in the elementary grammar of things, there is no distinction between 'cause' and 'effect.'"</p><p>So, why do we perceive time as flowing <em>forward</em>? Rovelli notes that, although time disappears on extremely small scales, we still obviously perceive events occur sequentially in reality. In other words, we observe entropy: Order changing into disorder; an egg cracking and getting scrambled.</p><p>Rovelli says key aspects of time are described by the second law of thermodynamics, which states that heat always passes from hot to cold. This is a one-way street. For example, an ice cube melts into a hot cup of tea, never the reverse. Rovelli suggests a similar phenomenon might explain why we're only able to perceive the past and not the future.</p><p style="margin-left: 20px;">"Any time the future is definitely distinguishable from the past, there is something like heat involved," Rovelli wrote for the <a href="https://www.ft.com/content/ce6ef7b8-429a-11e8-93cf-67ac3a6482fd" target="_blank"><em>Financial Times</em></a>. "Thermodynamics traces the direction of time to something called the 'low entropy of the past', a still mysterious phenomenon on which discussions rage."</p>
The strange subjectivity of time<p>Time moves differently atop a mountain than it does on a beach. But you don't need to travel any distance at all to experience strange distortions in your perception of time. In moments of life-or-death fear, for example, your brain would release large amounts of adrenaline, which would speed up your internal clock, causing you to perceive the outside world as moving slowly.<br></p><p>Another common distortion occurs when we focus our attention in particular ways.</p><p style="margin-left: 20px;">"If you're thinking about how time is <em>currently</em> passing by, the biggest factor influencing your time perception is attention," Aaron Sackett, associate professor of marketing at the University of St. Thomas, told <em><a href="https://gizmodo.com/why-does-time-slow-down-and-speed-up-1840133782" target="_blank">Gizmodo</a></em>.<em> "</em>The more attention you give to the passage of time, the slower it tends to go. As you become distracted from time's passing—perhaps by something interesting happening nearby, or a good daydreaming session—you're more likely to lose track of time, giving you the feeling that it's slipping by more quickly than before. "Time flies when you're having fun," they say, but really, it's more like "time flies when you're thinking about other things." That's why time will also often fly by when you're definitely <em>not</em> having fun—like when you're having a heated argument or are terrified about an upcoming presentation."</p><p>One of the most mysterious ways people experience time-perception distortions is through psychedelic drugs. In an interview with <a href="https://www.theguardian.com/books/2018/apr/14/carlo-rovelli-exploding-commonsense-notions-order-of-time-interview" target="_blank"><em>The Guardian</em></a>, Rovelli described a time he experimented with LSD.</p><p style="margin-left: 20px;">"It was an extraordinarily strong experience that touched me also intellectually," he said. "Among the strange phenomena was the sense of time stopping. Things were happening in my mind but the clock was not going ahead; the flow of time was not passing any more. It was a total subversion of the structure of reality."<br></p><p>It seems few scientists or philosophers believe time is completely an illusion.</p><p style="margin-left: 20px;">"What we call <em>time</em> is a rich, stratified concept; it has many layers," Rovelli told <em><a href="https://physicstoday.scitation.org/do/10.1063/PT.6.4.20190219a/full/" target="_blank">Physics Today</a>.</em> "Some of time's layers apply only at limited scales within limited domains. This does not make them illusions."</p>What <em>is</em> an illusion is the idea that time flows at an absolute rate. The river of time might be flowing forever forward, but it moves at different speeds, between people, and even within your own mind.
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