Plasminogen Activator Inhibitor 1, Cell Senescence, and Aging-Related Diseases

Cellular senescence, including replicative senescence (RS) and stress-induced premature senescence (SIPS), is a state of the permanent arrest of cell growth, which can occur in proliferative cells and post-mitotic cells. Cellular senescence is believed to contribute importantly to aging and aging-related diseases. Although several hypotheses, including telomere shortening, oncogene activation, oxidative stress, DNA damage, and mitochondrial dysfunction, have been proposed, the mechanisms underlying cellular senescence in either physiological or pathological conditions remain poorly understood. Plasminogen activator inhibitor 1 (PAI-1), a physiological inhibitor of tissue type and urokinase type of plasminogen activators (tPA and uPA), has multiple functions. PAI-1 expression increases with age and in many aging-related diseases. Importantly, increased PAI-1 expression is not only a marker but also a mediator of cell senescence induced by different stimuli in vitro and in vivo. This review focuses on the recent advance in the role of PAI-1 in cell senescence during aging and in aging-related diseases as well as the potential mechanisms by which PAI-1 promotes cell senescence.