The phenotype of an individual is the result of complex interactions between genome, epigenome and current, past and ancestral environment leading to a lifelong remodelling of the epigenomes. The genetic information expression contained in the genome is controlled by labile chromatin-associated epigenetic marks. Epigenetic misprogramming during development is widely thought to have a persistent effect on the health of the offspring and may even be transmitted to the next generation. The epigenome serves as an interface between the environment and the genome. Dietary factors, including folate involved in C1 metabolism, and other social and lifestyle exposures have a profound effect on many aspects of health including ageing and do so, at least partly, through interactions with the genome, which result in altered gene expression with consequences for cell function and health throughout the life course. Depending on the nature and intensity of the environmental insult, the critical spatiotemporal windows and developmental or lifelong processes involved, epigenetic alterations can lead to permanent changes in tissue and organ structure and function or to phenotypic changes that can (or cannot) be reversed using appropriate epigenetic tools. Moreover, the flexibility of epigenetic marks may make it possible for environmental, nutritional and hormonal factors or endocrine disruptors to alter, during a particular spatiotemporal window in a sex-specific manner, the sex-specific methylation or demethylation of specific CpG and/or histone modifications underlying sex-specific expression of a substantial proportion of genes. Moreover, genetic factors, the environment and stochastic events change the epigenetic landscape during the lifetime of an individual. Epigenetic alterations leading to gene expression dysregulation accumulate during ageing and are important in tumorigenesis and age-related diseases. Several encouraging trials suggest that prevention and therapy of age- and lifestyle-related diseases by individualised tailoring to optimal epigenetic diets or drugs are conceivable. However, these interventions will require intense efforts to unravel the complexity of these epigenetic, genetic and environment interactions and to evaluate their potential reversibility with minimal side effects.
