Scientists Identify Natural Protein That Mimics The Effects of Exercise

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What if you could get a lot of the benefits of exercise, without moving a muscle? A class of naturally occurring proteins called Sestrins might be able to mimic such metabolic effects, a new study suggests, although so far the results have only been observed in mice and fruit flies.

An instant exercise pill for humans is still some way off then – don't give up your gym membership just yet – but the new findings could further research into helping the physically impaired and injured keep their bodies in healthy shape.

During experiments, a team led by researchers from the University of Michigan found that suppressing Sestrins in flies and mice had a negative impact on how effective their exercise was; but by increasing Sestrin levels, the test subjects got some of the benefits of exercise without actually doing any.

"Sestrin upregulation mimics both molecular and physiological effects of exercise, suggesting that it could be a major effector of exercise metabolism," write the researchers in their published paper.

The team started with Drosophila flies, fashioning a makeshift insect treadmill in the lab. They compared the running and flying of flies (bred to lack the ability to make Sestrin) against flies bred to overexpress the proteins, and also looked at a normal group of flies.

This normal control group of flies showed improved endurance and better flying ability after three weeks of training – but the same improvements weren't seen in the flies that had their Sestrin production inhibited.

In the flies with Sestrin overexpression, the researchers observed their capabilities went beyond the control group, even when they weren't doing any exercise.

The effects seem to go beyond endurance too: another experiment on mice showed that animals without Sestrin didn't get the same boost in aerobic capacity, respiration, and fat burning usually associated with exercise.

In a related study on mice, produced in collaboration with some of the same researchers, the overexpression of Sestrin was shown to also help combat muscle atrophy – so Sestrin treatments could potentially be used to protect broken limbs inside casts, for example.

These findings could also be helpful in care for the elderly, the researchers point out, enabling older people who aren't as mobile as they used to be to still get some of the same benefits as they would from hitting the gym twice a week.

Of course, there's no evidence yet that any of these effects can be replicated in humans, though it has been well established that our muscles produce more Sestrin during exercise, so there is enough here to warrant future research.

It's also encouraging that the same effects were noted in both flies and mice during the study, making it perhaps more likely that the muscles of other animals – including humans possibly – might work the same way too. If so, more research will be needed to find out for sure.

"We propose that Sestrin can coordinate these biological activities by turning on or off different metabolic pathways," says physiologist Jun Hee Lee from the University of Michigan.

"This kind of combined effect is important for producing exercise's effects."

The research has been published in Nature Communications.

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A protein called Sestrin might be responsible for many of the benefits of a good workout

Date: January 13, 2020

Source: Michigan Medicine - University of Michigan

Summary: Researchers recently found that Sestrin, a naturally occurring protein in the body, mimicked the benefits of exercise in flies and mice.

Whether it be a brisk walk around the park or high intensity training at the gym, exercise does a body good. But what if you could harness the benefits of a good workout without ever moving a muscle?

Michigan Medicine researchers studying a class of naturally occurring protein called Sestrin have found that it can mimic many of exercise's effects in flies and mice. The findings could eventually help scientists combat muscle wasting due to aging and other causes.

"Researchers have previously observed that Sestrin accumulates in muscle following exercise," said Myungjin Kim, Ph.D., a research assistant professor in the Department of Molecular & Integrative Physiology. Kim, working with professor Jun Hee Lee, Ph.D. and a team of researchers wanted to know more about the protein's apparent link to exercise. Their first step was to encourage a bunch of flies to work out.

Taking advantage of Drosophila flies' normal instinct to climb up and out of a test tube, their collaborators Robert Wessells, Ph.D. and Alyson Sujkowski of Wayne State University in Detroit developed a type of fly treadmill. Using it, the team trained the flies for three weeks and compared the running and flying ability of normal flies with that of flies bred to lack the ability to make Sestrin.

"Flies can usually run around four to six hours at this point and the normal flies' abilities improved over that period," says Lee. "The flies without Sestrin did not improve with exercise."

What's more, when they overexpressed Sestrin in the muscles of normal flies, essentially maxing out their Sestrin levels, they found those flies had abilities above and beyond the trained flies, even without exercise. In fact, flies with overexpressed Sestrin didn't develop more endurance when exercised.

The beneficial effects of Sestrin include more than just improved endurance. Mice without Sestrin lacked the improved aerobic capacity, improved respiration and fat burning typically associated with exercise.

"We propose that Sestrin can coordinate these biological activities by turning on or off different metabolic pathways," says Lee. "This kind of combined effect is important for producing exercise's effects."

Lee also helped another collaborator, Pura Muñoz-Cánoves, Ph.D., of Pompeu Fabra University in Spain, to demonstrate that muscle-specific Sestrin can also help prevent atrophy in a muscle that's immobilized, such as the type that occurs when a limb is in a cast for a long period of time. "This independent study again highlights that Sestrin alone is sufficient to produce many benefits of physical movement and exercise," says Lee.

Could Sestrin supplements be on the horizon? Not quite, says Lee. "Sestrins are not small molecules, but we are working to find small molecule modulators of Sestrin."

Additionally, adds Kim, scientists still don't know how exercise produces Sestrin in the body. "This is very critical for future study and could lead to a treatment for people who cannot exercise."

https://www.sciencedaily.com/release...0113075830.htm