The PAI-1 protein is generated by the SERPINE1 gene. You might recall the discovery of a small human population with a loss of function mutation in this gene and longer lives then peers without the mutation. Here researchers map the relationships between PAI-1 and cellular senescence; PAI-1 is important in enabling onset of the senescent state. The accumulation of senescent cells with age is thought to be a meaningful contribution to degenerative aging, and the longevity of the PAI-1 loss of function population provides another piece of evidence in support of that hypothesis – to go along with all of the biochemical data, evidence of rejuvenation in aged animals following clearance of senescent cells, and promising clinical trials of senolytic drugs.
In this study, we aim to illustrate a pathway map of PAI-1, highlighting its contributions to cellular senescence and aging. PAI-1 is a critical component in the iniation of cellular senescence, and our findings underscore the pivotal role of the SERPINE1 gene in this process. Targeting PAI-1 offers a promising strategy to mitigate cellular senescence and associated age-related conditions such as emphysema, arteriosclerosis, organ fibrogenesis, and thrombosis. The publicly available PAI-1 pathway map will aid researchers in understanding the various molecules involved in modulating this pathway in pathological and physiological contexts. This resource provides insights for identifying other related molecules participating in this signaling network and may lead to innovative pharmacological means for managing cellular senescence and addressing diseases linked to PAI-1.
Accumulating evidence, including our laboratory’s research, positions PAI-1 as a molecular signature of cellular senescence and a potential inducer and mediator of maturation. Our research team is currently exploring the essential function of PAI-1 and the fibrinolytic system in age-related fibrotic lung conditions through pharmacological PAI-1 inhibitors. In our ongoing and future studies, we aim to further clarify the crucial function of PAI-1 in cellular senescence and its connections to the fibrinolytic system, particularly in age-associated mortality and morbidity.
