Aging of Mesenchymal Stem Cells Missing Link in IPF

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 DESCRIPTION (provided by applicant): The incidence of IPF and other pulmonary disorders increases with age independent of exposure to common environmental risk factors. Little is known about how age increases the risk for lung diseases. The lack of understanding the relationship between aging and the inability of the lung to repair after injury, as occurs in IPF, leads to an urgent need for more research in the field. Our own work has demonstrated an increase of susceptibility to chronic lung injury in aged mice. Additionally, we have described that bone marrow derived mesenchymal stem cells (B-MSCs) obtained from old mice are deficient in their multi-linage potential and in their capacity to respond to soluble factors. However, what are the biological consequences of an aged endogenous B-MSCs and why they exhibit a functional impairment is not well known. Our published and preliminary data supports the overarching and unique hypothesis that defective lung repair in aging is associated with dysfunctional activation, proliferation, and mobilization of B-MSCs. In the present revised project, we will focus on the effect of age on B-MSCs biology by comparing B-MSCs isolated from young and old donors and in the characteristics of B-MSCs during chronic Injury, by comparing B-MSCs isolated from IPF patients and age-matched and young controls. We are confident this will help us to understand the pathogenesis of other age-associated lung diseases and provide insights for the development of novel strategies for tissue repair.