Gene polymorphisms associated with the plasma levels of fibrinogen, factor VII, 
and plasminogen activator inhibitor 1 (PAI-1)-hemostasis proteins that help to 
predict the risk of atherothrombotic disease-were compared in 124 healthy 
individuals > or = 100 years old and 130 young, healthy individuals to identify 
genetic influences on extreme longevity. We investigated the restriction 
fragment length polymorphism G/A-455 located in the promoter of the 
beta-fibrinogen gene, the guanine insertion/deletion polymorphism 4G/5G in the 
promoter of the PAI-1 gene, and the R353Q substitution polymorphism in exon 8 of 
the factor VII gene. Alleles and genotypes associated with elevated plasma 
levels of fibrinogen and factor VII were found with similar frequencies in 
centenarians and in the comparison group. However, in centenarians there was a 
significantly higher frequency of the 4G allele and of the homozygous 4G4G 
genotype associated with high PAI-1 levels. Since high PAI-1 is considered a 
predictor of recurrent myocardial infarction in young men, it is intriguing that 
the corresponding genetic marker is more frequent in centenarians who have 
escaped major age-related atherothrombotic disease and reached the extreme 
limits of human life. Homozygosity for the 4G allele, despite its association 
with impaired fibrinolysis, is compatible with successful aging.