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The central role of muscle stem cells in regenerative failure with aging

Nature Medicine volume 21, pages 854–862 (2015)Cite this article

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Abstract

Skeletal muscle mass, function, and repair capacity all progressively decline with aging, restricting mobility, voluntary function, and quality of life. Skeletal muscle repair is facilitated by a population of dedicated muscle stem cells (MuSCs), also known as satellite cells, that reside in anatomically defined niches within muscle tissues. In adult tissues, MuSCs are retained in a quiescent state until they are primed to regenerate damaged muscle through cycles of self-renewal divisions. With aging, muscle tissue homeostasis is progressively disrupted and the ability of MuSCs to repair injured muscle markedly declines. Until recently, this decline has been largely attributed to extrinsic age-related alterations in the microenvironment to which MuSCs are exposed. However, as highlighted in this Perspective, recent reports show that MuSCs also progressively undergo cell-intrinsic alterations that profoundly affect stem cell regenerative function with aging. A more comprehensive understanding of the interplay of stem cell–intrinsic and extrinsic factors will set the stage for improving cell therapies capable of restoring tissue homeostasis and enhancing muscle repair in the aged.

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Figure 1: The role of MuSCS in tissue homeostasis with aging.

Debbie Maizels/Nature Publishing Group

Figure 2: Extrinsic and intrinsic regulators of MuSC function are altered in aging.

Debbie Maizels/Nature Publishing Group

Figure 3: Evidence in support of intrinsic 'memory' in aged and rejuvenated MuSC populations.

Debbie Maizels/Nature Publishing Group

Figure 4: Biophysical regulation of muscle stem cells in aging.

Debbie Maizels/Nature Publishing Group

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Acknowledgements

We apologize to those investigators whose important work we were unable to cite or describe in depth owing to the limited scope and space constraints of this Perspective. We are grateful for support from Muscular Dystrophy Association grant 217821 (A.T.V.H.); support from the US National Institutes of Health (NIH) grant R00AG042491 (B.D.C.); and The Baxter Foundation, California Institute for Regenerative Medicine (CIRM) grants RB5-07469 and TR3-05501, and NIH grants AR063963, AG020961, AG044815, and NS089533 (H.M.B.).

Author information

Author notes

  1. Benjamin D Cosgrove and Andrew T V Ho: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Microbiology and Immunology, Baxter Laboratory for Stem Cell Biology, and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA

    Helen M Blau & Andrew T V Ho

  2. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York, USA

    Benjamin D Cosgrove

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  1. Helen M Blau
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  2. Benjamin D Cosgrove
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  3. Andrew T V Ho
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Correspondence to Helen M Blau.

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Blau, H., Cosgrove, B. & Ho, A. The central role of muscle stem cells in regenerative failure with aging. Nat Med 21, 854–862 (2015). https://doi.org/10.1038/nm.3918

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