Aging of the immune system causes reductions in muscle stem cell populations, promotes their shift to a fibrogenic phenotype, and modulates sarcopenia

FASEB J. 2019 Jan;33(1):1415-1427. doi: 10.1096/fj.201800973R. Epub 2018 Aug 21.

Abstract

Aging is associated with diminished muscle mass, reductions in muscle stem cell functions, and increased muscle fibrosis. The immune system, especially macrophages, can have important roles in modulating muscle growth and regeneration, suggesting that the immune system may also have significant influences on muscle aging. Moreover, the immune system experiences changes in function during senescence, suggesting that regulatory interaction between muscle cells and the immune system may also change during aging. In this study, we performed bone marrow transplantations between age-mismatched donor and recipient mice to test the influence of the age of the immune system on muscle aging. Transplantation of young bone marrow cells into old recipients prevented sarcopenia and prevented age-related change in muscle fiber phenotype. Transplantation of old bone marrow cells into young animals reduced satellite cell numbers and promoted satellite cells to switch toward a fibrogenic phenotype. We also demonstrated that conditioned media from young, but not old, bone marrow cells promoted myoblast proliferation in vitro, and we found that factors released by young bone marrow cells were more supportive of myotube differentiation in vitro. Together, our results demonstrate that aging of bone marrow cells promotes the age-related reduction of satellite cell number and function and contributes to sarcopenia.-Wang, Y., Wehling-Henricks, M., Welc, S. S., Fisher, A. L., Zuo, Q., Tidball, J. G. Aging of the immune system causes reductions in muscle stem cell populations, promotes their shift to a fibrogenic phenotype, and modulates sarcopenia.

Keywords: bone marrow transplantation; macrophage; muscle fibrosis; satellite cell; skeletal muscle.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / physiology*
  • Animals
  • Biomarkers / metabolism
  • Bone Marrow Cells / pathology
  • Cell Differentiation
  • Cell Proliferation
  • Cellular Senescence / physiology
  • Female
  • Fibrosis
  • Hematopoietic Stem Cell Transplantation
  • Immune System / physiology*
  • Macrophages / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle Fibers, Skeletal / physiology
  • Sarcopenia / pathology*
  • Satellite Cells, Skeletal Muscle / pathology*

Substances

  • Biomarkers