Research Paper|Volume 13, Issue 10|pp 13421—13429

Systemic NF-κB-mediated inflammation promotes an aging phenotype in skeletal stem/progenitor cells

Anne Marie Josephson¹, Kevin Leclerc¹, Lindsey H. Remark¹, Emma Muiños Lopeź¹, Philipp Leucht^1,²

¹NYU Grossman School of Medicine, NYU Langone Orthopedics, New York, NY 10016, USA
²NYU Grossman School of Medicine, Department of Cell Biology, New York, NY 10016, USA

Received: December 2, 2020Accepted: May 11, 2021Published: May 25, 2021

https://doi.org/10.18632/aging.203083

Copyright: © 2021 Josephson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Aging tissues undergo a progressive decline in regenerative potential. This decline in regenerative responsiveness has been attributed to changes in tissue-specific stem cells and their niches. In bone, aged skeletal stem/progenitor cell dysfunction is characterized by decreased frequency and impaired osteogenic differentiation potential. This aging phenotype ultimately results in compromised regenerative responsiveness to injury. The age-associated increase of inflammatory mediators, known as inflamm-aging, has been identified as the main culprit driving skeletal stem cell dysfunction.

Here, we utilized a mouse model of parabiosis to decouple aging from inflammation. Using the Nfkb1^-/- mouse as a model of inflamm-aging, we demonstrate that a shared systemic circulation between a wild-type and Nfkb1^-/- mouse results in an aging phenotype of the wild-type skeletal stem and progenitor cells, shown by CFU-fs and osteogenic and adipogenic differentiation assays. Our findings demonstrate that exposure to an inflammatory secretome results in a phenotype similar to the one observed in aging.