Admission free
Dr. Bas Zwaan, Associate professor, Leiden University:
‘Old genes in a new environment: The role of gene x environment interactions in determining lifespan and ageing’
co-referee Prof. Martien Groenen, Animal Breeding and Genetics Group, Wageningen University
In humans, the genes shaped during our evolutionary history in thrifty circumstances interact with the affluent conditions of present day societies. This mismatch between our ‘old’ genes and our ‘new’ environments seems to be related to the explosive increase in type-2 diabetes and obesity. Subject of this lecture is the study of natural genetic variation and the interaction between the selective and other environments, with particular emphasis on the Insulin/IGF signalling pathway and its targets
Abstract of Zodiac lecture 1 April 2008
Along with climate change, dealing with an increasingly elderly population is probably the most pressing challenge in developed and developing societies. This challenge is exacerbated by the recent dramatic shift in our environment from the thrifty one in which we evolved to one of a rich and plentiful diet, a lack of exercise and a new set of stresses. The consequence is that our genetic make-up is functioning in a highly novel environment. In other words, Genotype-by-Environment (GxE) interactions have become of paramount importance as is evident from the burgeoning issues of type-2 diabetes and obesity. To describe and understand these GxE interactions is crucial to making real progress in developing new societal and clinical strategies; we try to contribute to this by using model organisms with sufficient experimental power to yield lists of the crucial components that can then be examined for their precise roles in our society.
Summary
Ageing is in part determined by the genes (G) individuals inherit, and in part by the environment (E) in which the individuals live and their genes must function. Both contribute to the variation in lifespan, ageing and health in human populations we observe today. However, these factors interact (GxE); the effects of genes on the adult phenotype depend on the environment in which they are expressed. In humans, the genes shaped during our evolutionary history in thrifty circumstances interact with the affluent conditions of present day societies. Thus, there is a mismatch between our ‘old’ genes and our ‘new’ environments, as can be judged by the explosive increase in type-2 diabetes and obesity. Our research aims to describe the mechanisms of the interactions of genes with adult environments, and how these affect the ageing phenotype. Clear candidate genes and mechanisms for ageing and lifespan have emerged from mutant and genetically manipulated model organisms under laboratory conditions. However, these results can not be applied directly to human populations because it is unknown to what extent such genes contribute to variation in natural populations or affect the ageing phenotype in (natural) environments other than the laboratory. The study of natural genetic variation and the interaction between the selective and other environments is the subject of this lecture, with particular emphasis on the Insulin/IGF signalling pathway and its targets. I will review and discuss our recent data from two model insects, the fruit fly Drosophila melanogaster and the tropical butterfly Bicyclus anynana, in which the interactions between the genotype and the environment were studied at the level of gene expression, physiology, life history, through to behaviour.
Curriculum Vitae
Bas Zwaan received his doctorate cum laude in October 1993. During his PhD research he developed an experimental evolutionary framework in which to study the genetic and environmental aspects of ageing and longevity, in particular using artificial selection in Drosophila melanogaster. Following a postdoc abroad in the laboratory of Linda Partridge (UCL, UK), he incorporated the model organism Bicyclus anynana into ageing research in Paul Brakefield’s laboratory, while still continuing to work on Drosophila. Several years ago he established a cross-faculty initiative of Evolutionary Medicine which is founded on the mutual interest in the evolution of ageing and understanding the mechanisms of ageing and longevity. The groups of Prof. Rudi Westendorp (Gerontology) and Prof. Eline Slagboom (Molecular Epidemiology), and the Evolutionary Biology group have since then developed a strong Leiden research programme on ageing. Recently, through the initiative and under the coordination of the Leiden research groups a European Network of Excellence, LifeSpan, was funded (http://www.lifespannetwork.nl; FP6 036894) for the period 2007-2012. LifeSpan seeks to integrate research into development and ageing. This collaboration provides the necessary links to allow extrapolation of his research results to applied aspects of human ageing and age-related health problems. Bas Zwaan is an Associate Professor since December 2001.