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Somatic mutagenesis in satellite cells associates with human skeletal muscle aging
Karolinska Inst, Ctr Innovat Med, Dept Biosci & Nutr, S-14157 Huddinge, Sweden..
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
Karolinska Inst, Dept Lab Med, Div Clin Physiol, S-14186 Huddinge, Sweden..
Karolinska Inst, Ctr Innovat Med, Dept Biosci & Nutr, S-14157 Huddinge, Sweden..
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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
NATURE PUBLISHING GROUP , 2018. Vol. 9, article id 800
National Category
Cell and Molecular Biology
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URN: urn:nbn:se:uu:diva-348850DOI: 10.1038/s41467-018-03244-6ISI: 000425935100013PubMedID: 29476074OAI: oai:DiVA.org:uu-348850DiVA, id: diva2:1198611
Funder
Swedish Research CouncilSwedish Society of MedicineMarianne and Marcus Wallenberg FoundationKnut and Alice Wallenberg FoundationWallenberg FoundationsScience for Life Laboratory - a national resource center for high-throughput molecular bioscienceAvailable from: 2018-04-18 Created: 2018-04-18 Last updated: 2018-04-18Bibliographically approved

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Johansson, Anna C. V.

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