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Nat Commun. 2018 Feb 23;9(1):800. doi: 10.1038/s41467-018-03244-6.

Somatic mutagenesis in satellite cells associates with human skeletal muscle aging.

Author information

1
Department of Biosciences and Nutrition, Center for Innovative Medicine, Karolinska Institutet, 14157, Huddinge, Sweden. irene.franco@ki.se.
2
Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, 75237, Uppsala, Sweden.
3
Division of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institutet, 14186, Huddinge, Sweden.
4
Department of Biosciences and Nutrition, Center for Innovative Medicine, Karolinska Institutet, 14157, Huddinge, Sweden.
5
Science for Life Laboratory, Department of Biochemistry and Biophysics (DBB), Stockholm University, 10691, Stockholm, Sweden.
6
Science for Life Laboratory, Department of Physics, Chemistry and Biology, Linköping University, 58183, Linköping, Sweden.
7
Italian Institute for Genomic Medicine (IIGM), 10126, Turin, Italy.
8
Department of Applied Science and Technology, Politecnico di Torino, 10129, Turin, Italy.
9
Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, 10126, Turin, Italy.
10
Center for Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, 20132, Milan, Italy.
11
Department of Biosciences and Nutrition, Center for Innovative Medicine, Karolinska Institutet, 14157, Huddinge, Sweden. Maria.Eriksson.2@ki.se.

Abstract

Human aging is associated with a decline in skeletal muscle (SkM) function and a reduction in the number and activity of satellite cells (SCs), the resident stem cells. To study the connection between SC aging and muscle impairment, we analyze the whole genome of single SC clones of the leg muscle vastus lateralis from healthy individuals of different ages (21-78 years). We find an accumulation rate of 13 somatic mutations per genome per year, consistent with proliferation of SCs in the healthy adult muscle. SkM-expressed genes are protected from mutations, but aging results in an increase in mutations in exons and promoters, targeting genes involved in SC activity and muscle function. In agreement with SC mutations affecting the whole tissue, we detect a missense mutation in a SC propagating to the muscle. Our results suggest somatic mutagenesis in SCs as a driving force in the age-related decline of SkM function.

PMID:
29476074
PMCID:
PMC5824957
DOI:
10.1038/s41467-018-03244-6
[Indexed for MEDLINE]
Free PMC Article

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