NYU Grossman School of Medicine, NYU Langone Orthopedics, New York, NY 10016, USA.
NYU Grossman School of Medicine, Department of Cell Biology, New York, NY 10016, USA.
Aging (Albany NY). 2021 May 25;13(10):13421-13429. doi: 10.18632/aging.203083.
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.
衰老组织的再生潜能逐渐下降。这种再生反应能力的下降归因于组织特异性干细胞及其龛位的变化。在骨骼中，衰老的骨骼干细胞/祖细胞功能障碍的特征是频率降低和成骨分化潜能受损。这种衰老表型最终导致对损伤的再生反应能力受损。被称为“炎症衰老”的炎症介质的年龄相关性增加被认为是导致骨骼干细胞功能障碍的主要罪魁祸首。在这里，我们利用联体动物模型将衰老与炎症分离。利用 Nfkb1 小鼠作为炎症衰老的模型，我们证明，野生型和 Nfkb1 小鼠之间共享的全身循环会导致野生型骨骼干细胞和祖细胞出现衰老表型，这可以通过集落形成单位（CFU-fs）和成骨及成脂分化实验来证明。我们的研究结果表明，暴露于炎症分泌组会导致类似于衰老过程中观察到的表型。
