A genetic mutation in SERPINE1, the gene responsible for Plasminogen Activator Inhibitor-1 (PAI-1), seems to have ties back to leading a longer, healthier life. While complete PAI-1 deficiency can lead to a life-threatening clotting disorder, individuals who were heterozygous for this mutation seem to enjoy an extended lifespan on average.
New research validates the PAI-1 knockout mouse as a preclinical genetic model of human depression, while demonstrating that this knockout also serves as a model for antidepressant resistance. Not only that, but this new research shows PAI-1 is involved in depression separately from the tPA-BDNF axis. As a result, PAI-1 could be a novel target for developing new treatments for major depressive disorder.