Genetics: Longevity Assurance

Although the study of longevity genes in humans is still in its infancy, there is overwhelming evidence that the human life span has a significant heritable component (Caurnil and Kirkwood, 2001). Studies of twins have suggested that genetics accounts for up to 30 percent of the variance in human longevity. An even stronger relationship between genetics and longevity was observed by analyzing the genetics of centenarians and their families. In one study, the siblings of centenarians were three to four times more likely to reach age 100 than were siblings of non-centenarians. Another study showed that the immediate Table 1 SOURCE: Author ancestors of Jeanne Calment of France (who died at the age of 122, after breaking the record for human life span) were ten times more likely to reach age 80 than was the ancestral cohort (Robine and Allard, 1998).

Examination of the frequency of known gene variants in very old individuals has led to identification of five putative human longevity genes. A major problem in the identification of human longevity genes is that different studies often reach different conclusions. Scientists generally agree that the genes for apolipoprotein E (apoE), angiotensin-converting enzyme (ACE), and histocompatibility locus antigen (HLA-DR) are genuine longevity genes (see Table 1). Genes for superoxide dismutase 2 (SOD2) and tyrosine hydroxylase (TH) have also been implicated in longevity. Human genes whose association with longevity is debated include those for cytochrome P-450, certain blood coagulation factors, and homocysteine methylation (MTHFR). In 2001, Thomas Perls, Luis Kunkel, and colleagues reported the identification in one family of a region on human chromosome IV that predisposes for exceptional longevity (Puca et al., 2001). However, the individual gene or genes responsible have not yet been identified.

There are many genes in humans whose variants reduce life expectancy (e.g., the tumor suppressor gene, MSH2). However, these are not true longevity variants because they are known only to reduce the life span, not to extend it. The apoE gene, involved in lipoprotein metabolism, has been found to affect longevity most consistently. At least five studies have detected the apoE-epsilon2 variant more frequently in centenarians than in the general population. Even so, it has been suggested that the apoE is a not a longevity gene, but that the apoE-epsilon4 variant causes premature death by promoting atherosclerosis (Gerdes et al., 2000). This matter, which remains to be resolved, illustrates another difficulty in classifying human longevity genes.