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

作者：Oh Juhyun; Sinha Indranil; Tan Kah Yong; Rosner Bernard; Dreyfuss Jonathan M; Gjata Ornela; Tran Peter; Shoelson Steven E; Wagers Amy J^*

来源：Aging-US, 2016, 8(11): 2871-2896.

DOI：10.18632/aging.101098

• satellite cell
• skeletal muscle
• aging
• regeneration

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

• 出版日期2016-11