Models of genetic and non-genetic factors in human longevity

Abstract

There is little doubt today that ageing is a partially inherited characteristic with the environment playing an equally important role. In this project our aim was to elucidate the gene-gene and gene-environment interactions relevant to ageing through the use of theoretical models and the evolutionary theories of ageing. With our first model we establish for the first time the plausibility of an immunogenetic trade-off between reproduction and survival under infection pressure from the environment while making detailed predictions for the expected point of balance in two different countries, one developing and the other developed, together with predictions about the surprising speed with which an evolutionary transition between the two states can occur. In our second model we develop a detailed simulation program based on epidemiological studies to account for the action of the apolipoprotein gene in western populations, its association with lifestyle parameters, and its evolution over the last 2 million years. We suggest a two-stage history for evolution of Apo E where the establishment of the E3 allele took place during the shift of humanoids to a meat-based diet and the £2 allele started to appear slowly as a rare mutation. Later, with the spread of agriculture and the increasing longevity of humans, the alleles began to be selected more and more towards their current frequencies. Finally, we show how a combination of socioeconomic factors and the stochasticity of mortality can be the driving forces behind the heterogeneity seen in human populations today and reveal the key factors generating this heterogeneity.