Is This Protein A Substitution For Exercise?

There’s no denying a trip to the gym or a jog around the block is great for our bodies – in particular our muscle tone. But what if the benefits of a workout could be harnessed without budging a single muscle?  


A little protein called Sestrin might just be capable of doing that. Michigan Medicine researchers studying a class of this naturally-occurring protein have discovered that it can mimic many of exercise’s effects in the case of flies and mice. While this might seem a little removed from humans, it is thought the findings could eventually help scientists to combat such issues as muscle-wasting due to aging and other causes.


The protein’s seeming link to exercise has already been noted in the past with researchers observing that Sestrin – a metabolic regulator – accumulates in muscle following exercise. In a bid to learn more, My-ungjin Kim, Ph.D., a research assistant professor in the Department of Molecular & Integrative Physiology working with professor Jun Hee Lee, Ph.D. and a team of researchers, embarked on some testing which involved encouraging a group of flies to essentially work out.


This first step involved harnessing the natural instinct of Drosophila flies to climb up and out of test tubes with collaborators at Wayne State University in Detroit, Robert Wessells, Ph.D. and Alyson Sujkowski, building a fly treadmill of sorts. With this contraption, they trained the flies for three weeks and compared the physical activity of normal flies with flies bred to lack the ability to make Sestrin.  


Under Armour

The results were intriguing. “Flies can usually run around four to six hours at this point and the normal flies’ abilities improved over that period,” says Lee. In comparison, the flies without Sestrin did not improve with exercise. Furthermore, when the muscles of the normal flies were overexpressed in Sestrin, which basically maxes out their Sestrin levels, they discovered those flies had abilities that far exceeded that of the trained flies even without exercise. 


We propose that Sestrin can coordinate these biological activities by turning on or off different metabolic pathways,” says Lee, who has also assisted another collaborator, Pura Muñoz-Cánoves, Ph.D., of Pompeu Fabra University in Spain, to show that the muscle-specific Sestrin can also help to prevent muscle atrophy where there is immobilisation such as when a limb has been cast for a long period of time. Lee continues, “This independent study again highlights that Sestrin alone is sufficient to produce many benefits of physical movement and exercise.”


While these findings are profound and might hold the potential for some kind of treatment in the future for people who, for one reason or another, cannot exercise, there is still a lot that scientists do not know about this intriguing protein in terms of how exercise produces it in the body. “This is very critical for future study and could lead to a treatment for people who cannot exercise… Sestrins are not small molecules, but we are working to find small molecule modulators of Sestrin,” says Lee. For now, we will have to settle for our skeletal muscle’s ability to adapt its mass to changes in activity the old fashioned way.

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