Guest Editorial: Genetic and Phenotypic Markers Among Centenarians

Extract

Decision Editor: John E. Morley, MB, BCh

IN 1825, Benjamin Gompertz proposed that mortality rate increased exponentially with age. Since then, most researchers have accepted that this rule indeed applies to the age range around the average life expectancies of many species, humans included. However, at extreme old age an exception to the rule exists. At very old age, mortality begins to decelerate in species such as medflies ⁽¹⁾, Caenorhabditis elegans⁽²⁾, and humans ⁽³⁾. Why does mortality decelerate? Most likely it is because frailer individuals drop out of the population, leaving behind a more robust cohort that continues to survive. Because these frail individuals drop out of the population, the distribution of certain genotypes and other survival-related attributes in a cohort changes with older and older age ⁽⁴⁾. This selecting-out process is termed demographic selection.

The effect of demographic selection is exemplified by the drop out with extreme age of the apolipoprotein E ε-4 allele ⁽⁵⁾. Rebeck and colleagues noted the frequency of the ε-4 allele to decrease markedly with advancing age, even among nonagenarians and centenarians with dementia ⁽⁶⁾. One of its counterparts, the ε-2 allele, becomes more frequent with advanced age. Consistent with these observations are the findings reported by Frisoni and colleagues in this issue ⁽⁷⁾. Presumably the drop out at earlier age of the ε-4 allele is because of its association with “premature” mortality secondary to Alzheimer's disease and heart disease.