Stem Cell Exhaustion in the Aging Lung

Stem cell activity declines with age throughout the body. In some cases this is because stem cells become less active in response to changes in the signaling environment. In other cases, the cells are damaged or the populations greatly reduced. The consequence of this decline is that fewer daughter somatic cells are produced to make up losses, repair damage, and maintain tissue function. A slow decline into organ dysfunction results, contributing to the onset of age-related disease, disability, and mortality. Finding ways to reverse this process is a very important component of of the broader field of rejuvenation research.

Tissue stem cell exhaustion is a key hallmark of aging, and in this study, we characterised its manifestation in the distal lung. We compared the lungs of 3- and 22-month old mice. We examined the gross morphological changes in these lungs, the density and function of epithelial progenitor populations and the epithelial gene expression profile. Bronchioles became smaller in their cross-sectional area and diameter. We found that bronchiolar cell density remained stable with aging, but inferred rates of progenitor cell self-renewal and differentiation were reduced, indicative of an overall slowdown in cellular turnover.

Alveolar Type II progenitor cell density and self-renewal were maintained per unit tissue area with aging, but rates of inferred differentiation into Type I cells, and indeed overall density of Type I cells was reduced. Microarray analysis revealed age-related changes in multiple genes, including some with roles in proliferation and differentiation, and in IGF and TGFβ signalling pathways. By characterising how lung stem cell dynamics change with aging, this study will elucidate how they contribute to age-related loss of pulmonary function, and pathogenesis of common age-related pulmonary diseases.

Link: https://doi.org/10.1038/s41598-020-66966-y

Comments

What is the actual hold up in treating stem cell exhaustion in vairous tissues with replacement stem cells?

Would replacing satelite cells in muscles help sarcopenia? What are the technical roadblocks to doing so at the moment?

Posted by: jimofoz at July 11th, 2020 3:50 AM

@jimofoz
It seems that the implanted stem cells usually die (but provide beneficial signalling). On the rare occasion they get grafted there is risk of teratoma (cells start forming tissues organs or even a mini fetus)

Posted by: cuberat at July 11th, 2020 5:28 PM

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