Researchers from the INCLIVA Health Research Institute, the Clinical Hospital of Valencia, and the University of Valencia (UV) have participated in a study, the results of which have just been published in Science, which paves the way for a better understanding of muscle injury. The work will enable, in the future, the application of interventions that accelerate its repair both in the physiological field, in sports performance, and probably also in the clinical field, in the frail or sarcopenic patient (loss of muscle mass and strength in older adults).
The main finding of this study is the discovery that muscle cells are capable of regenerating rapidly and autonomously and not only through the intervention of stem cells, as was believed until now. The objective of the work in which Mari Carmen Gómez-Cabrera, professor of the Department of Physiology of the UV and researcher of this project for the INCLIVA, and the researcher Esther García have participated was to clarify the mechanisms by which the muscle fibre regenerates after moderate damage such as that induced by physical exercise.
The mechanisms by which muscle is repaired in the event of very serious muscle injury are well described and involve a type of cell called a muscle satellite cell. In less severe and much more common muscle injuries, such as those that occur after exercise and, probably also, in those associated with the muscle aging process itself, the repair mechanism was not well established.
According to Gómez-Cabrera, "contrary to what happens in other cells in our body, our muscles are made up of cells that have multiple nuclei. The muscle cell is damaged when, for example, we suffer a trauma (a blow) but also when we do physical exercise. Exercises with an important eccentric component (a type of contraction in which the muscle generates tension while increasing its length), such as walking down stairs, can cause muscle damage". In addition, the professor at the University of Valencia specifies: "muscle damage is very common in athletes and repair mechanisms are very important in the fields of sports medicine, traumatology and rehabilitation".
The expert highlights the importance of this study, "which has made it possible to find that the repair mechanism for non-severe muscle injuries does not involve, as was originally thought, muscle stem cells or satellite cells".
What happens in a damaged fibre is that the cores of the fibre itself are attracted to the place of damage, which accelerates their repair."
Mari Carmen Gómez-Cabrera, Professor, Department of Physiology, UV
The study is the result of a collaboration between the Pompeu Fabra University (UPF), the National Centre for Cardiovascular Research (CNIC) and CIBERNED, in Spain; and the João Lobo Antunes Institute of Molecular Medicine (iMM), in Portugal.
The nuclei near the damage area use the release of messenger RNA as a repair mechanism, which is translated into proteins, that act as building blocks to resolve the muscle injury and return the fibre to its functionality.
Three types of experimental models have been used in this work. They have included athletes who have performed an exercise protocol they knew to induce muscle damage, mice, and various cell models: myotubes and muscle myofibres. The repair mechanism they have described is preserved in the three models studied and represents a very efficient and highly relevant protection mechanism for minor muscle injuries.
In addition, the study has been fundamental in the housing units, as well as the equipment acquired by INCLIVA through the ERDF funds derived from the Valencian Community strategy for research on aging and frailty.
INCLIVA's work for this study has been developed thanks to funding received from the Carlos III Health Institute CB16 / 10/00435 (CIBERFES), from the Ministry of Science and Innovation (PID2019-110906RB-I00 / AEI / 10.13039 / 501100011033); 109_RESIFIT, CSIC General Foundation; PROMETEO / 2019/097 of the Ministry of Health of the Valencian Government and FEDER Funds.
Mª Carmen Gómez-Cabrera is coordinator of the Research Group on Exercise, Nutrition and Healthy Lifestyle and co-coordinator of the Transversal Program on Aging and Associated Diseases of INCLIVA. She is also part of CIBERFES (Centre for Biomedical Research on Frailty and Healthy Aging Network). Predoctoral researcher Esther García has also intervened in the work, through the design and development of in vivo studies with exercise, both in humans and in mice, over the last 18 months.
Roman, W., et al. (2021) Muscle repair after physiological damage relies on nuclear migration for cellular reconstruction. Science. doi.org/10.1126/science.abe5620.