Opposite effects of interleukin 10 common gene polymorphisms in cardiovascular diseases and in successful ageing: genetic background of male centenarians is protective against coronary heart disease

Centenarians escape, or at least delay, age associated diseases that normally cause mortality at earlier ages. Considerable evidence supports involvement of genetic components to longevity. Accordingly, siblings of centenarians have a marked increased probability of living to 100 years of age. The major trait of the offspring of centenarians is a significantly reduced prevalence of cardiovascular diseases. Patients with atherosclerosis have a proinflammatory genotype, and tight control of inflammatory reactions might decrease the incidence of atherosclerosis. Gene polymorphisms for proinflammatory cytokines seem to contribute considerably to the risk of coronary heart disease, including acute myocardial infarction, so alleles associated with susceptibility to acute myocardial infarction are expected to be less represented in genetic backgrounds that favour longevity. On the other hand, in Italian centenarian men, the frequency of the genotype associated with interleukin 10 (-1082GG) is associated with significantly increased production of the antiinflammatory cytokine interleukin 10. In two different populations from north and south Italy, analysis of genotype distributions showed a significantly higher frequency of the -1082GG genotype among oldest old participants than in controls and patients with acute myocardial infarction. Conversely, the frequency of the -1082AA genotype, associated with low production of interleukin 10, was significantly higher in patients with acute myocardial infarction than in controls and oldest old participants. High production of interleukin 10 thus is protective for acute myocardial infarction and a determinative parameter for longevity. People with exceptional longevity possess genetic factors that modulate ageing processes and, in particular, factors protective for cardiovascular disease. This supports the opinion that a genetic background protective against cardiovascular diseases is a component of longevity. Our immune system has evolved to control pathogens, so proinflammatory responses are likely to be programmed by evolution to resist fatal infections, and low production of interleukin 10 is associated with an increased resistance to pathogens. Increased concentrations of interleukin 10, however, might better control inflammatory responses induced by chronic vessel damage and reduce the risk of atherogenetic complications. These conditions might results in an increased chance of long life in an environment with a reduced load of antigens ( that is, pathogens).