Our “genes” are not fixed: “Plasticity” of the genotype by epigenetic mechanisms => important for the phenotypic impact of nutrition. • Histone and DNA modifications have impact on gene transcription efficiency. Methylation (more stable) and acetylation (more flexible) have impact on chromatin structures. • Epigenetic modifications have impact on offspring, embryo development, ageing and disease development or prevention => example: Dutch Hunger Winter.  Health status of future parents are very important for the future health of children.  Early healthy nutrition & lifestyle essential for successful healthy life & “ageing”.

1. Epigenetica – de invloed van voedingsstoffen op genexpressie Michael MüllerNetherlands Nutrigenomics Centre & Nutrition, Metabolism and Genomics GroupDivision of Human Nutrition, Wageningen University

2. Nutritional science tries to define:What is healthy?

3. We have a tsunami of health problems

4. Why is more effective prevention very important now: Because we should stay healthy as long as possible 100 % Health/ “Quality of life” time

5. We are different

6. Nutrigenomics = modern nutritional science: Quantification of the nutritional genotype-phenotype Lifestyle Nutrition Environment

7. Duality of biological information:Epigenetic & Genetic

8. Epigenetics The study of reversible heritable changes in gene function that occur without a change in the sequence of nuclear DNA.

10. Received, Recorded, Remembered & Revealed

11. Environmental sensitivity of the epigenome

12. Molecular mechanisms that mediate epigenetic phenomena DNA methylation (CpGdinucleotides) Histone modifications

13. Epigenetic inheritance In somatic cells, epigenetic information is replicated during mitosis along with the DNA sequence. The mechanism for replication of DNA methylation is well understood but the mechanism for replication of histone modifications is not.

15. Longer life

16. High risk cancer, diabetes, obesity

18. Epigenetic modifications associated with very early life

19. Extensive epidemiologic studies have suggested that adult disease risk is associated with adverse environmental conditions early in development. Although the mechanisms behind these relationships are unclear, an involvement of epigenetic dysregulation has been hypothesized. Here we show that individuals who were prenatally exposed to famine during the Dutch Hunger Winter in 1944–45 had, 6 decades later, less DNA methylation of the imprinted IGF2 gene compared with their unexposed, same-sex siblings. The association was specific for periconceptional exposure, reinforcing that very early mammalian development is a crucial period for establishing and maintaining epigenetic marks. These data are the first to contribute empirical support for the hypothesis thatearly-life environmental conditions can cause epigenetic changes in humans that persist throughout life. => healthy nutrition of the mother is essential

20. Early prevention of obesity: Role of epigenetics

21. The father is also important for healthMetabolic risk can be conferred via the paternal lineage (Cell & Nature 2011)

23. Early healthy nutrition & lifestyle essential for successful healthy life & “ageing”.