Historical demography and longevity genetics: Back to the future.

Research into the genetic component of human longevity can provide important insights in mechanisms that may protect against age-related diseases and multi-morbidity. Thus far only a limited number of robust longevity loci have been detected in either candidate or genome wide association studies. One of the issues in these genetic studies is the definition of the trait being either lifespan, including any age at death or longevity, i.e. survival above a diverse series of thresholds. Likewise heritability and segregation research have conflated lifespan with longevity. The heritability of lifespan estimated across most studies has been rather low. Environmental factors have not been sufficiently investigated and the total amount of genetic variance contributing to longevity has not been estimated in sufficiently well-defined and powered studies. Up to now, genetic longevity studies lack the required insights into the nature and size of the genetic component and the optimal strategies for meta-analysis and subject selection for Next Generation Sequencing efforts. Historical demographic data containing deep genealogical information may help in estimating the best definition and heritability for longevity, its transmission patterns in multi-generational datasets and may allow relevant additive and modifying environmental factors such as socio-economic status, geographical background, exposure to environmental effects, birth order, and number of children to be included. In this light historical demographic data may be very useful for identifying lineages in human populations that are worth investigating further by geneticists.