Anyone who wants to live a healthy life must also exercise, that much is clear. But that is not always easy to fit into a busy life with a family, work and all those other things you still want to do. There are also people who cannot exercise due to illness or limitations. How ideal would it be if there was a pill that mimics the effect of exercise? Researchers have come a long way.

They have now discovered a substance that appears to imitate the physical boost of an exercise session, at least in the cells of rodents. The discovery could lead to a new treatment method for muscle diseases, heart failure and dementia.

Exercise is better
“We cannot replace movement. Sports are important at all levels,” emphasizes lead researcher Bahaa Elgendy. “If you can exercise, I would continue with that and take up physical activity. But there are so many cases that require a replacement.”

Exercise is good for body and mind. Elgendy, professor of anesthesiology at the Washington Universityand his colleagues focused mainly on the beneficial physical effects, more precisely: on strengthening the metabolism and the growth of muscle cells.

Special proteins
A medicine that can strengthen muscles and prevent muscle weakness can be a great solution for the elderly and people who, for whatever reason, can no longer exercise enough. It could even potentially reduce the side effects of other drugs, such as obesity drugs, which involve the loss of both fat and muscle, the researchers think.

The metabolic changes caused by exercise begin with the activation of certain proteins called estrogen-related receptors (ERRs). After ten years of research, Elgendy and his colleagues have discovered a substance called SLU-PP-332 that can do exactly that: activate these receptors, just like exercise. The researchers discovered that this substance increased a fatigue-resistant type of muscle fiber in mice, while also improving the animals’ endurance when they had to run on a treadmill.

All kinds of improvements
It was certainly not an easy job to identify this super-effective SLU-PP-332. Before this, the researchers spent a long time studying the ERRs and how they bind to molecules that activate them. To improve on their discovery, they designed new molecules that further enhanced the interaction with the receptors, producing a more powerful response than SLU-PP-332 can produce on its own. The team also optimized the molecules for other characteristics, such as stability and toxicity.

The researchers then compared the potency of SLU-PP-332 with that of the new compounds by looking at the RNA, a measure of gene expression, of about 15,000 genes in rat heart muscle cells. The new molecules led to a greater increase in RNA, indicating that they more powerfully simulate the effects of exercise.

Dementia treatment
And that can help against all kinds of diseases. Animal studies show that SLU-PP-332 provides benefit against obesity, heart failure and declining kidney function with aging. The results of the new research show that the new substances can have the same effects.

But the benefits go even further. Activation of estrogen-related receptors could also counteract harmful processes in the brains of Alzheimer’s patients. And while SLU-PP-332 cannot enter the brain, some of the new substances have been developed in such a way that they can. “ERRs play an important role in all these diseases,” says Elgendy. “If you have a substance that can activate them effectively, you can generate so many beneficial effects.”

That is why he and his colleagues want to further test the new components in animals. They are also already looking at the options for treating dementia, among other things. A promising substance, which we will hopefully hear more about soon.