Idiopathic pulmonary fibrosis (IPF) appears to be significantly driven by the presence of senescent cells in the lungs. Other forms of fibrosis in other organs have been similarly linked to senescent cells. Increased cellular senescence is a feature of aging, and indeed is one of the root causes of aging. These cells secrete a potent mix of signals that induce inflammation, damage tissue structures, and change the behavior of nearby cells for the worse. In this context the results presented here are intriguing; the authors of this open access paper find that IPF patients have more senescent bone marrow stem cells.
There are a few ways to think about this. The first is that aging is a global phenomenon of accumulating molecular damage throughout the body, and people with enough damage to be predisposed to clinical levels of lung fibrosis are going to exhibit more pronounced measures of aging everywhere else as well. The second is that stem cells are negatively affected by high levels of inflammation, inflammatory signaling can spread widely by following the circulatory system, and the inflammatory conditions of IPF in lung tissues may thus be harming stem cell populations throughout the body. Lastly, one could argue causation in the other direction, as the researchers do here, suggesting that senescence of stem cells in bone marrow is a contributing factor to the development of IPF.
Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease characterized by a progressive and irreversible loss of lung function though accumulation of scar tissue. Aging is considered the main risk factor for IPF. Along with others, we have demonstrated that there is an increase in markers of cell senescence in lung fibroblasts from IPF patients. Additionally, we have shown that, in animal models of lung injury, aged bone marrow-derived mesenchymal stem cells (B-MSCs) have decreased protective activity. This is in contrast to what we had previously described in young animal models of pulmonary fibrosis, where infusion of B-MSCs isolated from normal young donors in the initial stages of the injury results in a decrease in collagen deposition in the lung.
Therefore, we aimed to determine the differences in the biological and functional characteristics of B-MSCs from healthy individuals and IPF patients within the same age range. Characterization of IPF B-MSCs shows an increase in cell senescence linked to an upsurge of senescence-associated secretory phenotypes (SASPs) promoting a proinflammatory milieu and increasing deposition of components from the extracellular matrix. Our data suggest that extrapulmonary alterations in B-MSCs from IPF patients might contribute to the pathogenesis of the disease.
The consequences of having senescent B-MSCs are not completely understood, but the decrease in their ability to respond to normal activation and the risk of having a negative impact on the local niche by inducing inflammation and senescence in the neighboring cells suggests a new link between B-MSC and the onset of the disease.