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

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-?B 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-?B signaling in muscle satellite cells or myofibers on recovery after damage. These studies reveal that NF-?B activity in differentiated myofibers is sufficient to drive dysfunction of muscle regenerative cells via cell-non-autonomous mechanisms. Inhibition of NF-?B, 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-?B inhibitor, decreased inflammatory gene expression and improved repair in aged muscle. Together, these studies identify a unique NF-?B 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.

SUBMITTER: Oh J 

PROVIDER: S-EPMC5191876 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature