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Researchers discover how the muscle regenerates after exercise

Publicado em 30 setembro 2020

Por Chloé Pinheiro | Agência FAPESP

Researchers from USP (University of São Paulo) found that the regeneration of muscles promoted by aerobic exercise is mediated by changes in oxygen consumption by satellite cells – a type of muscle tissue stem cell. The finding may help in the recovery of injuries and in combating the loss of muscle mass associated with age.

Previous work has already shown that exercise with overload, such as weight training, was able to induce an increase in the number of satellite cells. In aerobic physical training, however, tissue is known to improve its capacity, but repair mechanisms associated with satellite cells have not been studied.

The USP group noted that aerobic activities promote a desired expansion of satellite cells and revealed important metabolic changes behind the phenomenon. The investigation was conducted during Phablo Sávio Abreu Teixeira’s postdoctoral research, with the support of a scholarship from FAPESP.

“We found that there is a reduction in oxygen consumption in satellite cells, differently from what happens in the rest of the muscle tissue, where exercise increases the demand for oxygen. It is the first time that it is possible to observe how aerobic exercise influences the metabolism of mitochondria. of these cells, and the effect of that on muscle regeneration “, explains Abreu to FAPESP Agency.

To understand the mechanism, the postdoctoral student conducted a series of experiments with animals at USP’s Chemistry Institute, under the supervision of Professor Alicia Kowaltowski, who has been dedicated to the study of mitochondria since the 1990s and is part of the team at the Research Center of Redox Processes in Biomedicine (Redoxoma). The findings were published in the Journal of Cachexia, Sarcopenia and Muscle.

“We discovered at least part of the mechanisms that lead to the improvement of muscle regeneration, and knowing them is the first step towards one day being able to interfere in this process”, comments Kowaltowski.

Multiple steps

The research was carried out in phases, from experiments with mice divided into two groups. Part of them was submitted to a battery of aerobic exercises, on the treadmill, for a period of five weeks, and part remained sedentary.

At the end of the training period, the researchers carried out tests to verify whether the animals submitted to the exercise program had in fact improved their aerobic capacity. Then, the muscle tissues of both groups were injured, a stage in which it was observed that the exercised muscles had improved their regenerative capacity.

“First, we observed that the trained animals had more recently formed muscle fibers, in addition to less fibrous tissue deposition and less signs of inflammation. Thus, we confirmed that the muscle tissue of the exercised animals was in fact better repaired,” says Abreu.

After identifying that the muscles had improved their repair capacity, the next step was to investigate the changes in satellite cells isolated from these exercised animals. Proteins that regulate the progression of the quiescent (dormant) cell and its activation, so that self-renewal or differentiation occurs, were increased in these cells. “In addition, they showed a delay in differentiation, which confirmed our findings”, continues Abreu.

As the researcher explains, satellite cells in the adult individual are responsible for regenerating and preserving muscle tissue. For this, they remain in quiescence, a state of numbness that maintains tissue homeostasis. Throughout their lives, they will be activated in the face of some injury or wear, as in physical exercise or in the injury induced by Abreu in the laboratory mice.

From there, part of them differentiates to form cells that will compose the tissue, part starts a process of self-renewal, which gives rise to new satellite cells so that this cycle continues to happen.

“These cells are constantly activated, but over time they can become fatigued and stop self-renewing – a phenomenon observed in dystrophies and when there is loss of muscle mass, such as cachexia and sarcopenia”, comments Abreu. “If we have more renewed cells, it means that we have more cells able to regenerate the tissue”, he adds.

Therefore, Abreu found that exercise maintains the ability to regenerate muscle tissue and contributes to the recovery of injuries. And, finally, he measured the oxygen expenditure in the satellite cells of the rodents undergoing the training, in search of answers about what led to that behavior. “The surprising thing is that they consume less oxygen, as if they were more economical”, says Abreu.

The finding contradicts the initial hypothesis of the researchers, who believed that, once the muscle improves its oxidative capacity with aerobic exercise, and the satellite cells are anchored on the surface of the musculoskeletal tissue (hence the name satellite), they would also improve their capacity aerobic.

The role of mitochondria

The cellular respiration process occurs in the mitochondria, cellular structures that, until recently, were thought to be only responsible for the production of energy for the organism. “In recent years, we have increasingly discovered how they are involved in various processes,” says Kowaltowski.

To confirm whether the oxygen consumption of mitochondria was really the cause of the self-renewal of satellite cells, Kowaltowski and Abreu carried out two more tests: they mimicked the effect of reducing oxygen consumption with medicines in cultures in vitro and, in a second moment, they transplanted the exercised cells in sedentary animals.

The reduction of oxygen consumption in the cells studied in vitro was able to improve stem cell self-renewal. In the transplant, there was no change in the number of cells repaired, but there was a decrease in inflammation, a finding suggestive of better muscle recovery.

The idea now is to investigate the effects of decreased mitochondrial oxygen consumption and the pathways involved in the self-renewal of satellite cells. “In short, we need to understand why by inhibiting cellular respiration we increase muscle recovery”, comments the scientist.

It may be that, in the future, it will be possible to replicate this phenomenon to treat age-related muscle loss and problems such as cancer and aging, a process that is still often irreversible.