Biology and genetics of human longevity

Human longevity is a multifactorial trait, which includes a network of genes combined with strong environmental factors. Biological and clinical characteristics of human beings are the result of the interaction between genes and the environment. Until about 1950 centenarians were quite rare in low-mortality countries. Since then the number has more than doubled every 10 years and even the number of 105+ year old people is now increasing. This proliferation of centenarians is mainly a result of the decrease in oldest-old mortality and probably due to changes of lifestyle and health care. Although studies of Danish twin pairs seem to indicate that genetic influence on human lifespan is only moderate, several gene loci contribute to longevity. Data are evident from the Italian Centenarian Study for apoproteinB, tyrosine hydroxylase and mitochondrial DNA loci among others studied (superoxide dismutases, ie. SOD1 and SOD2, poly(ADP-ribose)polymerase and thyroid peroxidase). The data from the Danish Centenarian Study confirm the findings from the studies of French and Finnish centenarians on apolipoprotein E genotype with a higher frequency of epsilon-2 and lower frequency of epsilon-However, the apoE genotype seems not to be a key determinant of exceptional longevity: in 105+ year olds the epsilon-4 allele was found in 4 out of 19 persons. Italian centanarians have a paradoxically marked hypercoagulability as demonstrated also by genetic markers. Also the von Willebrand factor was increased independently of the blood group. Studies on such atherosclerosis risk factors as lipoprotein(a) and homocysteine revealed that these two parameters may be high in Italian centenarians, but their genetic control possibly attenuates with age, and environmental factors may play a major role in the oldest-old persons. Also interaction among genes is possible. All these studies suggest that longevity is a phoenornenon depending on multiple genetic and environmental factors. Further studies are needed for a better understanding of the complex interactions which allow people to reach a very old age.