Strength training activates cellular waste elimination, interdisciplinary research reveals

The removal of damaged cellular components is essential for the maintenance of body tissues and organs. An international research team led by the University of Bonn has made important discoveries about the mechanisms of cellular waste removal, showing that muscle training activates these mechanisms. These findings could provide the basis for new therapies for heart failure and nervous diseases, and even be useful for manned space missions.

A corresponding article was published in the latest issue of the journal Current Biology.

Muscles and nerves are durable, high-performance organs whose cellular components are subject to constant wear and tear. The BAG3 protein plays a critical role in removing damaged components, identifying them and ensuring they are enclosed within cell membranes to form an “autophagosome.”

Autophagosomes are like garbage bags in which cellular waste is collected and then shredded and recycled. The research team led by Professor Jörg Höhfeld from the Institute of Cell Biology at the University of Bonn has shown that strength training activates BAG3 in the muscles. This has important implications for the removal of cellular waste, as BAG3 must be activated to effectively bind damaged cellular components and promote membrane wrapping.

An active elimination or cleaning system is essential for the long-term preservation of muscle tissue. “Impairment of the BAG3 system actually causes progressive muscle weakness in children as well as heart failure, one of the most common causes of death in Western industrialized countries,” explains Professor Höhfeld.

Important implications for athletic training and physiotherapy

The study was carried out with the active participation of sports physiologists from the German Sports University Cologne and the University of Hildesheim. Professor Sebastian Gehlert from Hildesheim emphasises the importance of these results: “We now know at what level of strength training intensity the BAG3 system should be activated. This allows us to optimise the training programmes of top athletes and help physiotherapy patients to develop their muscles better.” Professor Gehlert is also using these results to support the members of the German Olympic team.

The BAG3 system isn’t just active in muscles. Mutations in the BAG3 system can lead to a nerve disease called Charcot-Marie-Tooth syndrome (named after the scientist who discovered the disease). This disease causes nerve fibers in the arms and legs to die, leaving the individual unable to move their hands or feet.

By studying cells from affected patients, the research team showed that some manifestations of the syndrome cause defective regulation of BAG3 elimination processes. These results demonstrate the considerable importance of this system for tissue preservation.

Unexpected regulation opens door to new therapies

When the researchers looked more closely at the activation of BAG3, they were surprised by what they observed. “Many cellular proteins are activated by the attachment of phosphate groups in a process called phosphorylation. With BAG3, on the other hand, the process is reversed,” explains Professor Jörg Höhfeld, also a member of the Transdisciplinary Research Area (TRA) Life and Health at the University of Bonn.

“BAG3 is phosphorylated in resting muscles and the phosphate groups are removed upon activation.” At this point, phosphatases become the main focus: the enzymes that remove phosphate groups.

To identify the phosphatases that activate BAG3, Höhfeld is collaborating with chemist and cell biologist Maja Köhn from the University of Freiburg. “Identifying the phosphatases involved is a key step,” she explains, “so that we can continue to develop substances that can potentially influence BAG3 activation in the body.”

This research could open up new therapeutic possibilities for muscle weakness, heart failure and nerve diseases.

Relevant for space travel

The work on the BAG3 system is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation) through a research unit headed by Professor Höhfeld. In addition, Höhfeld receives funding from the German Space Agency, as the research is of interest for manned space missions.

Professor Höhfeld emphasizes: “BAG3 is activated by mechanical force. But what happens in the absence of mechanical stimulation? In astronauts living in weightlessness, for example, or in intensive care patients immobilized on a ventilator?”

In such cases, the lack of mechanical stimulation quickly leads to muscle atrophy, which Höhfeld attributes at least in part to the non-activation of BAG3. According to him, drugs developed to activate BAG3 could help in such situations. That is why Höhfeld’s team is preparing experiments to be carried out aboard the International Space Station (ISS). Research into BAG3 could thus help us reach Mars one day.