Mechanisms of Dysfunction in Senescent Pulmonary Endothelium

Age-dependent changes in pulmonary endothelium contribute to worsened clinical outcomes in elderly individuals. Due to altered pulmonary endothelial responses, older participants have increased vulnerability to infection-related sequelae, higher prevalence of pulmonary hypertension, mitigated DNA repair mechanisms, and attenuated parenchymal healing. Aberrant signaling in pulmonary endothelium undergird these clinical processes. In this review, we provide an overview of the work that has elucidated age-related molecular derangements in pulmonary endothelial cells. In particular, we summarize studies describing mishandling of intracellular reactive oxygen species, pathological nitric oxide signaling, and deficient recruitment of endothelial stem cell precursors. We conclude with a summary of potential future avenues of investigation. The signaling pathways associated with pulmonary endothelial senescence reviewed herein suggest a number of putative therapeutic drug targets. Further elucidation of the cellular processes associated with aging in the pulmonary endothelium may provide critical insights into the rational design of therapies that may subvert or even reverse the effects of aging on a molecular level.