A new study by researchers at Karolinska Institutet in Sweden who investigated mutations in muscle’s stem cells (satellite cells) shows how an unexpectedly high number of mutations which resulted in impaired cell regeneration leading to aging of skeletal muscles. The study is published in Nature Communications.
“What is most surprising is the high number of mutations. We have seen how a healthy 70-year-old has accumulated more than 1,000 mutations in each stem cell in the muscle, and that these mutations are not random but there are certain regions that are better protected,” explains Maria Eriksson, Professor at the Department of Biosciences and Nutrition at Karolinska Institutet.
The mutations occur during natural cell division, and the regions that are protected are those that are important for the function or survival of the cells. Nonetheless, the researchers were able to identify that this protection declines with age.
“We can demonstrate that this protection diminishes the older you become, indicating an impairment in the cell’s capacity to repair their DNA. And this is something we should be able to influence with new drugs,” explains Maria Eriksson.
“We achieved this in the skeletal muscle tissue, which is absolutely unique. We have also found that there is very little overlap of mutations, despite the cells being located close to each other, representing an extremely complex mutational burden,” explains the study’s first author, Irene Franco, Postdoc in Maria Eriksson’s research group.
The researchers will continue their work to find out if physical activity influences number of accumulated mutations.
“We aim to discover whether it is possible to individually influence the burden of mutations. Our results may be beneficial for the development of exercise programmes, particularly those designed for an ageing population,” explains Maria Eriksson.
The researchers gained access to the muscle tissue used in the study via a close collaboration with clinical researchers, including Helene Fischer at the Unit for Clinical Physiology at Karolinska University Hospital.
Citation: Franco, Irene, Anna Johansson, Karl Olsson, Peter Vrtačnik, Pär Lundin, Hafdis T. Helgadottir, Malin Larsson, Gwladys Revêchon, Carla Bosia, Andrea Pagnani, Paolo Provero, Thomas Gustafsson, Helene Fischer, and Maria Eriksson. “Somatic mutagenesis in satellite cells associates with human skeletal muscle aging.” Nature Communications 9, no. 1 (2018). doi:10.1038/s41467-018-03244-6.
Research Funding: the Swedish Research Council, CIMED (Centre for Innovative Medicine), the David and Astrid Hagelén Foundation, the Swedish Society of Medicine, the Gun and Bertil Stohnes Foundation, the Osterman Foundation, the Marianne and Marcus Wallenberg Foundation, Wallenberg Advanced Bioinformatics Infrastructure and the EU Commission funding programme, Marie Skodowska-Curie
Adapted from press release by Karolinska Institutet.