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  3. Age-associated NF-κB signaling in myofibers alters the satellite cell niche and re-strains muscle stem cell function

Age-associated NF-κB signaling in myofibers alters the satellite cell niche and re-strains muscle stem cell function

  • Aging (Albany NY). 2016 Nov 14;8(11):2871-2896. doi: 10.18632/aging.101098.
Juhyun Oh 1 2 3,  Indranil Sinha 1 2 4,  Kah Yong Tan 1 2,  Bernard Rosner 5,  Jonathan M Dreyfuss 2 6,  Ornela Gjata 1,  Peter Tran 2,  Steven E Shoelson 2 7,  Amy J Wagers 1 2 3
Affiliations

Affiliations

  • 1 Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
  • 2 Joslin Diabetes Center, Boston, MA 02215, USA.
  • 3 Paul F. Glenn Center for the Biology of Aging, Harvard Medical School, Boston, MA 02115, USA.
  • 4 Division of Plastic Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • 5 Department of Biostatistics, Harvard School of Public Health, MA 02115, USA.
  • 6 Department of Biomedical Engineering, Boston University, Boston 02215, USA.
  • 7 Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
PMID: 27852976 DOI: 10.18632/aging.101098
Abstract

Skeletal muscle is a highly regenerative tissue, but muscle repair potential is increasingly compromised with advancing age. In this study, we demonstrate that increased NF-κB activity in aged muscle fibers contributes to diminished myogenic potential of their associated satellite cells. We further examine the impact of genetic modulation of NF-κB signaling in muscle satellite cells or myofibers on recovery after damage. These studies reveal that NF-κB activity in differentiated myofibers is sufficient to drive dysfunction of muscle regenerative cells via cell-non-autonomous mechanisms. Inhibition of NF-κB, or its downstream target Phospholipase A2, in myofibers rescued muscle regenerative potential in aged muscle. Moreover, systemic administration of sodium salicylate, an FDA-approved NF-κB Inhibitor, decreased inflammatory gene expression and improved repair in aged muscle. Together, these studies identify a unique NF-κB regulated, non-cell autonomous mechanism by which stem cell function is linked to lipid signaling and homeostasis, and provide important new targets to stimulate muscle repair in aged individuals.

Keywords

aging; regeneration; satellite cell; skeletal muscle.

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