Age-associated NF-κB signaling in myofibers alters the satellite cell niche and re-strains muscle stem cell function
Tan, Kah Yong
Dreyfuss, Jonathan M.
MetadataShow full item record
CitationOh, Juhyun, Indranil Sinha, Kah Yong Tan, Bernard Rosner, Jonathan M. Dreyfuss, Ornela Gjata, Peter Tran, Steven E. Shoelson, and Amy J. Wagers. 2016. “Age-associated NF-κB signaling in myofibers alters the satellite cell niche and re-strains muscle stem cell function.” Aging (Albany NY) 8 (11): 2871-2884. doi:10.18632/aging.101098. http://dx.doi.org/10.18632/aging.101098.
AbstractSkeletal 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.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:29739147