Nevertheless, it must be considered that the 4G allele, which might be associated with higher PAI-1 serum levels, is not necessarily a disadvantageous marker. The activity of the fibrinolytic system is reflected in circulating levels of tissue-type plasminogen activator (t-PA) and its most important inhibitor, PAI-1. Elevated t-PA antigen levels are strongly associated with elevated PAI-1 antigen and activity [26]. Increased levels of t-PA antigen have been shown to be a marker of risk for several thromboembolic diseases [27,28]. The pathophysiological background of this finding is controversial; one possible mechanism is the increased risk of arteriosclerotic plaque rupture under conditions of enhanced fibrinolysis. Thus, individuals with the 4G/4G allele may better balance increases in t-PA levels, and this could represent a possible mechanism for reduced fibrinolytic activity to be advantageous. This hypothesis is supported by evidence that thrombosis increases the expression and circulating levels of PAI-1 [29,30].

Nevertheless, the studied groups were small both in the cited 124 centenarians and in our study of 205 elderly individuals. Therefore, it cannot be excluded that differences between the results of these two studies are due to small numbers with the resulting statistical consequences. Moreover, we chose a group of persons who were 10-20 years younger than the centenarians, and this may also have contributed to the differing results.

On the basis of the results of our study, we suspect that other genetic variables and environmental conditions may be stronger predictors of longevity than the 4G/5G PAI-1 polymorphism. However, it should be acknowledged that the method of investigating single gene polymorphisms may identify only genes with a mono-causal genetic impact on health risks. Multiple logistic functions linking numerous genotypical and phenotypical characteristicsEriksson P, Kallin B, van t Hooft FM, Bavenholm P, Hamsten A () Allele-specific increase in basal transcription of the plasminogen-activator inhibitor gene is associated with myocardial infarction. Proc Natl Acad Sci USA: 
Margaglione M, Cappucci G, d'Addedda M, Colaizzo D, Giuliani N, Vecchione G, Mascolo G, Grandone E, Di Minno G () PAI-plasma levels in a general population without clinical evidence of atherosclerosis: relation to environmental and genetic determinants. Arterioscler Thromb Vasc Biol: 
Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Miletich JP () Arterial and venous thrombosis are not associated with the GG polymorphism in the promoter of the plasminogen activator inhibitor gene in a large cohort of US men. Circulation: 
Mannucci PM, Mari D, Merati G, Peyvandi F, Tagliabue L, Sacchi E, Taioli E, Sansoni P, Bertolini S, Franceschi C () Gene polymorphisms predicting high plasma levels of coagulation and fibrinolysis proteins. Arterioscler Thromb Vasc Biol: 
Henry M, Tregouet DA, Alessi MC, Aillaud MF, Visvikis S, Siest G, Tiret L, Juhan-Vague I () Metabolic determinants are much more important than genetic polymorphisms in determining the PAI-activity and antigen plasma concentrations. Arterioscler Thromb Vasc Biol: 
Grancha S, Estelles A, Tormo G, Falco C, Gilabert J, España F, Cano A, Segui R, Aznar J () Plasminogen activator inhibitor-(PAI-) promoter GG genotype and increased PAI-circulating levels in postmenopausal women with coronary artery disease. Thromb Haemost: 
Grant PJ () Plasminogen activator inhibitor-promoter GG genotype and plasma levels in relation to a history of myocardial infarction in patients characterized by coronary angiography. Arterioscler Thromb Vasc Biol: 
Roest M, van der Schouw YT, Banga JD, Tempelman MJ, de Groot PG, Sixma JJ, Grobbee DE () Plasminogen activator inhibitor G polymorphism is associated with decreased risk of cerebrovascular mortality in older women. Circulation: 
Nicoloso G, Hauert J, Kruithof EK, Van Melle G, Bachmann F () Fibrinolysis in normal subjects - comparison between plasminogen activator inhibitor and other components of the fibrinolytic system. Thromb Haemost: 
Ridker PM, Vaughan DE, Stampfer MJ, Manson JE, Hennekens CH () Endogenous tissue-type plasminogen activator and risk of myocardial infarction. Lancet: 
Jansson JH, Olofsson BO, Nilsson TK () Predictive value of tissue plasminogen activator mass concentration on long-term mortality in patients with coronary artery disease: a 5-year follow-up. Circulation: 
Fujii S, Abendschein DR, Sobel BE () Augmentation of plasminogen activator inhibitor type activity in plasma by thrombosis and by thrombolysis. J Am Coll Cardiol: 
Fujii S, Sawa H, Saffitz JE, Lucore CL, Sobel BE () Induction of endothelial cell expression of the plasminogen activator inhibitor type gene by thrombosis in vivo. Circulation: 
Grubic N, Stegnar M, Peternel P, Kaiser A, Binder BR () A novel G/A and the GG polymorphism within the promoter of the plasminogen activator inhibitor gene in patients with deep vein thrombosis. Thromb Res: