A genetic mutation in the SERPINE1 gene has been shown to protect against a number of conditions associated with biological aging including leukocyte telomere length (LTL), metabolism, and life span. SERPINE1 encodes plasminogen activator inhibitor-1 (PAI-1) in humans, a protein known to play a role in cellular senescence in vitro. The research team studied 177 members of an Amish community in Berne, Indiana, where there is a high incidence of the frameshift mutation. The group of individuals provided a unique opportunity to understand the connection between PAI-1 on human longevity. The study findings were recently published in Science Advances.
Shortened telomeres have been shown to be associated with multiple aging-related disorders. The study demonstrated that mean LTL length in SERPINE1 null carriers was 10% longer than in non-carriers of the mutation. In addition, type 2 diabetes was significantly less prevalent in mutation carriers and fasting insulin levels were measured to be 28% lower in carriers than in non-carriers.
"For the first time we are seeing a molecular marker of aging (telomere length), a metabolic marker of aging (fasting insulin levels) and a cardiovascular marker of aging (blood pressure and blood vessel stiffness) all tracking in the same direction in that these individuals were generally protected from age-related changes," Vaughan said. "That played out in them having a longer lifespan. Not only do they live longer, they live healthier. It's a desirable form of longevity. It's their 'health span.'"
In previously published research, it was shown that a PAI-1 inhibitor given mice dramatically slowed the aging process. The mice lived four times longer than the control group. The same drug is in phase two clinical trials in Japan to see if inhibiting PAI-1 can be used to help replenish blood cells in patients whose cell counts are depleted after undergoing chemotherapy.