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Genes involved in cardiovascular diseases (CVD) play an opposite role in human longevity. The alpha1-antitrypsin (AAT) is a serine-protease inhibitor required for the prevention of proteolytic tissue damage, by neutrophil elastase. The role of AAT in CVD has not been definitively assessed and its effect on longevity has not yet fully been studied. To clarify these points, we have studied the distribution of AAT allele variants in 3 cohorts: 127 young patients affected by acute myocardial infarction (AMI), 255 young controls and 143 centenarians from Sicily. The Z allele frequency was most frequent in centenarians (13.3%), intermediate in healthy young controls (3.1%) and less frequent in AMI patients (1.2%) (P = 0.0000001). The heterozygous MZ genotype was significantly over represented in centenarians (38/143) and under represented in AMI patients (3/127) with intermediate values in young controls (16/255) (P = 0.0000001). After adjustment for well-recognized AMI risk factors, the MZ genotype still predicted a significant negative risk factor for developing AMI in the Sicilian population. Thus, our data show a positive role of MZ heterozygosity in attainment of successful ageing linked to the positive effects of this genotype versus the cardiovascular ischemic diseases.

The genetics of the interaction between host and microbes plays an essential role in the survival of the individual and attainment of longevity. The activation of toll-like receptor (TLR)4 plays a key role in natural and clonotypic immune responses. We evaluated whether TLR4 genotype is a component of genetic background protective versus rickettsiosis and whether this background influences longevity. We genotyped for +896A/G TLR4 polymorphism 78 patients affected with Boutonneuse fever, 78 age-matched controls and 78 advanced age individuals from Sicily. The +869G allele, that attenuates receptor signalling, was significantly overrepresented in patients in comparison with age-matched controls. By analyzing data according to gender, this allele was significantly higher in female patients when compared to advanced age women. Pro-inflammatory responses are programmed to resist fatal infections. So, it is not surprising that the genetic background of people that survive to an advanced age may be protective against infections. However, this seems to occur in women but not in men. In a previous study, the +896G TLR4 allele was overrepresented in advanced age men and underrepresented in men affected by myocardial infarction. Thus, previous and present results tend to agree with the suggestion that men and women may follow different trajectories to reach longevity. For men it might be more important to control atherogenesis, whereas for women it might be more important to control infectious diseases.

Background and Aims: Centenarians display a lower incidence of vascular ischemic events. A high platelet count and increased QT dispersion (QTd) represents a risk factor for cardiovascular events. The aim of this study was to evaluate platelet count and QTd in healthy centenarians and to establish correlations between these two indices., Methods: 16 healthy centenarians (4 males, 12 females, range 100-105 years) living in a municipality of Eastern Sicily, and 40 healthy control subjects, divided into two groups: group A (N=20), age range 45-65 years, 7 males, 13 females; and group B (N=20), range 65-85 years, 6 males, 14 females, were examined. Platelets were counted using a blood analyzer and QTd was measured in standard 12-lead electrocardiograms. Differences in platelet count were assessed by one-way analysis of variance (ANOVA) and the Bonferroni test. Correlation coefficients between platelet count and QTd were calculated with the Spearman rank test., Results: Centenarians showed a lower platelet count compared with controls, which was significant with respect to older controls, group B (p<0.05). QTd values did not significantly differ between centenarians and controls. A significant correlation between QTd and platelet count was evident in centenarians but not in controls. This correlation became evident in control subjects with a platelet count < or = 240,000/mm3., Conclusions: We hypothesize that a reduced number of platelets and the maintenance of normal QTd may contribute to extreme longevity and protect centenarians from cardiovascular events.