Researchers at Michigan Medicine have found that a naturally occurring protein called Sestrin can mimic many of the effects of exercise in flies and mice. Published in Nature Communications, scientists believe that understanding the function of this protein could help combat muscle wasting due to aging and other causes.

Previous studies have observed that the protein Sestrin accumulates in the muscle after exercise. To find out more, the research team at the Department of Molecular & Integrative Physiology investigated on Drosophila flies. These flies are commonly used in investigations as they are small, produce many offspring, have easily discernible mutations, have only four pairs of chromosomes, and complete their entire life cycle in about 12 days.

Drosophila flies have a normal instinct to climb up and out of a test tube, and with collaborators from Wayne State University, Detroit, a fly treadmill was built. For three weeks, normal flies and flies lacking Sestrin were trained and compared to each other in their running and flying ability. They found that the normal flies’ ability to run around for four to six hours improved over time, but the flies without Sestrin didn’t improve in ability with exercise.

The team also investigated the ability that flies with an overexpression of Sestrin have against normal flies, maxing out their Sestrin levels. The overexpressed flies had abilities above and beyond the trained flies, even without exercise. However, they didn’t develop more endurance as they exercised.

In mice, those lacking Sestrin showed no improvements in aerobic capability, respiration, and fat burning typically associated with exercise.

The research teams suggest that Sestrin may play a role in different metabolic pathways that control different biological activities playing a major role in producing the effects of exercise. In another collaboration with the University of Spain, the researchers demonstrated that in muscle that’s been immobilised for a long time, such as when a limb is in a cast, muscle-specific Sestrin can help to prevent muscle atrophy.

There are many benefits linked to exercise that Sestrin seems to produce. We won’t be seeing any Sestrin supplements yet though, as they are big molecules. The researchers are working to find small molecule modulators of Sestrin and investigate how exercise produces Sestrin in the body, which could lead to potential treatments for people who aren’t able to exercise.