| Autor: |
Diptiman Chanda, Mohammad Rehan, Samuel R Smith, Kevin G Dsouza, Yong Wang, Karen Bernard, Deepali Kurundkar, Vinayak Memula, Kyoko Kojima, James A Mobley, Gloria A Benavides, Victor Darley-Usmar, Young-iL Kim, Jaroslaw W Zmijewski, Jessy S Deshane, Stijn De Langhe, Victor J Thannickal |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
eLife, Vol 10 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2050-084X |
| DOI: |
10.7554/eLife.68049 |
| Popis: |
Multicellular organisms maintain structure and function of tissues/organs through emergent, self-organizing behavior. In this report, we demonstrate a critical role for lung mesenchymal stromal cell (L-MSC) aging in determining the capacity to form three-dimensional organoids or ‘alveolospheres’ with type 2 alveolar epithelial cells (AEC2s). In contrast to L-MSCs from aged mice, young L-MSCs support the efficient formation of alveolospheres when co-cultured with young or aged AEC2s. Aged L-MSCs demonstrated features of cellular senescence, altered bioenergetics, and a senescence-associated secretory profile (SASP). The reactive oxygen species generating enzyme, NADPH oxidase 4 (Nox4), was highly activated in aged L-MSCs and Nox4 downregulation was sufficient to, at least partially, reverse this age-related energy deficit, while restoring the self-organizing capacity of alveolospheres. Together, these data indicate a critical role for cellular bioenergetics and redox homeostasis in an organoid model of self-organization and support the concept of thermodynamic entropy in aging biology. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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