Inhibition of NF-κB improves the stress resistance and myogenic differentiation of MDSPCs isolated from naturally aged mice

Jonathan D. Proto, Aiping Lu, Akaitz Dorronsoro, Alex Scibetta, Paul D. Robbins, Laura J. Niedernhofer, Johnny Huard

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

A decline in the regenerative capacity of adult stem cells with aging is well documented. As a result of this decline, the efficacy of autologous stem cell therapies is likely to decline with increasing donor age. In these cases, strategies to restore the function of aged stem cells would have clinical utility. Globally, the transcription factor NF-κB is up-regulated in aged tissues. Given the negative role that NF-κB plays in myogenesis, we investigated whether the age-related decline in the function of muscle-derived stem/progenitor cells (MDSPCs) could be improved by inhibition of NF-κB. Herein, we demonstrate that pharmacologic or genetic inhibition of NF-κB activation increases myogenic differentiation and improves resistance to oxidative stress. Our results suggest that MDSPC “aging” may be reversible, and that pharmacologic targeting of pathways such as NF-κB may enhance the efficacy of cell-based therapies.

Original languageEnglish (US)
Article numbere0179270
JournalPloS one
Volume12
Issue number6
DOIs
StatePublished - Jun 2017
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health grant AG043376 (Project 2 and Core A: PDR, Project 1 and Core B: LJN, Project 3: JH).

Publisher Copyright:
© 2017 Proto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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