A null mutation in SERPINE1 protects against biological aging in humans

Authors: Sadiya S. Khan, Sanjiv J. Shah, Ekaterina Klyachko, Abigail S. Baldridge, Mesut Eren, Aaron T. Place, Abraham Aviv, Eli Puterman, Donald M. Lloyd‐Jones, Meadow Heiman, Toshio Miyata, Sweta Gupta, Amy D. Shapiro, Douglas E. Vaughan - Science Advances 2017 cited by 155

mutation. Heterozygosity was associated with significantly longer leukocyte telomere length, lower fasting insulin levels, and lower prevalence of diabetes mellitus. In the extended Amish kindred, carriers of the null SERPINE1 allele had a longer life span. Our study indicates a causal effect of PAI-1 on human longevity, which may be mediated by alterations in metabolism. Our findings demonstrate the utility of studying loss-of-function mutations in populations with geographic and genetic isolation and shed light on a novel therapeutic target for aging.