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Somatic mutagenesis in satellite cells associates with human skeletal muscle aging
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Number of Authors: 14
2018 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, article id 800Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2018. Vol. 9, article id 800
Keyword [en]
Ageing, Genetics research, Muscle stem cells, Next-generation sequencing
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:su:diva-154850DOI: 10.1038/s41467-018-03244-6ISI: 000425935100013PubMedID: 29476074OAI: oai:DiVA.org:su-154850DiVA, id: diva2:1195861
Available from: 2018-04-06 Created: 2018-04-06 Last updated: 2018-04-06Bibliographically approved

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Franco, IreneLundin, PärHelgadottir, Hafdis T.Pagnani, Andrea
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Department of Biochemistry and BiophysicsScience for Life Laboratory (SciLifeLab)
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