Niels van den Berg | 22-01-2020 | Family matters: a genealogical inquiry into the familial component of longevity
Identifying genes that code for proteins associated to longevity is an important aspect of aging research. These longevity genes likely represent key mechanisms of a life-long decreased mortality and a decreased probability of age-related disease causing persons to be free of disease until old age (compression of morbidity towards the end of life). However, the identification of longevity genes has been challenging and only a handful of genetic variants have been shown to associate with longevity across multiple independent genome-wide linkage and association studies. The most compelling evidence was obtained for variants in the APOE and FOXO3A genes as they have been consistently identified with either genome[1]wide association studies or candidate gene studies. One of the main reasons for the limited success of genetic longevity studies is the uncertainty in defining the heritable longevity trait itself. The increased life expectancy of the past 200 years due to non-genetic/social factors such as improved hygiene, nutrition and medication. As a result, there are likely many phenocopies (a person who shows the characteristics of a genotype (survival into extreme ages) but where the underlying mechanism lies in non-genetic factors) among the long-lived persons selected for our genetic studies. To illustrate this, the number of centenarians (survivors to 100+ years) increased from 1 in 10,000 in 1994 to 1 in 5,000 in 2012. In this thesis I show that the solution to identifying longevity genes may lie in the familial clustering of longevity and the inclusion of persons with the heritable longevity trait (persons descending from a long-lived family) in future longevity research.