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

Nat Commun 2018 02 23;9(1):800. Epub 2018 Feb 23.

Department of Biosciences and Nutrition, Center for Innovative Medicine, Karolinska Institutet, 14157, Huddinge, Sweden.

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.

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Source
http://www.nature.com/articles/s41467-018-03244-6
Publisher Site
http://dx.doi.org/10.1038/s41467-018-03244-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824957PMC
February 2018
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