Epigenetics of Lifestyle

The concept of epigenetics refers nowadays to the long-lasting and inheritable gene expression states that are established in the absence of a change in the DNA sequence itself. The fast progress of the field in later times has provided scientists with novel understanding on how the environment in the wide sense, including nutrition, exercise, even behavior of the organisms, participates in the regulation of gene expression. The molecular mechanisms that mediate epigenetic regulation are principally DNA methylation, the post-translational modifications of the histones and the regulation by non-coding RNAs. They are intimately related to cell differentiation and developmental plasticity and relay environmental influences to the cell nucleus, thus bridging the gap between lifestyle and the genome. In this introductory chapter we offer a general vision of the well-documented effects of lifestyle choices and environmental impact on gene expression and present the reader with a general overview of the better known epigenetic mechanisms and the techniques most often used to study them.

There is strong evidence that the epigenetic regulation of gene transcription, by way of covalent modifications of DNA and DNA-associated proteins, and through microRNAs, is an essential process underlying neuronal plasticity and memory. This chapter brings the non-specialist reader up to speed on important concepts within memory research, focusing on the role of the hippocampus, the molecular regulation of synaptic strength, and the behavioral tools used to examine learning and memory in experimental animals. Next, we describe the close association that is observed between defective epigentic processes and impaired memory in several cognitive diseases. The bulk of the chapter is then devoted to describing three broad classes of technical approaches that have been used to better understand how DNA methylation, histone post-translational modification, and microRNAs might contribute to memory. We end the chapter with a discussion on the potential relevance of epigenetic processes in sustaining memory traces in the brain over very long periods of time.

Poor stress-coping is associated with a greater chance of developing a psychiatric illness such as post-traumatic stress disorder (PTSD) or depression. Lifestyle interventions which facilitate more appropriate responses to stress are much sought after. Exercise is one such intervention and is now commonly being prescribed as a cotreatment along with drugs for treating depression. Exercised rodents display reduced anxiety and impulsivity in a variety of behavioral paradigms. Rats exposed to psychological stress show differential epigenetic and gene expression mechanisms at the dentate gyrus (DG) after long-term voluntary exercise. Alterations within ERK MAPK signalling to chromatin seem to modulate the number of epigenetically marked neurons in the DG, improving cognitive responses to a stress-related event. Other lifestyle interventions such as nutrition or better maternal care in early life have been shown to induce changes at the epigenome which impact positively on mental health.

There is increasing evidence that the environment modifies individual genotypes through epigenetic mechanisms, creating behavioral traits and leaving persistent memories of past events. In post-mitotic cells such as neurons, chromatin modifications provide not only transient but also stable (or even permanent) epigenetic marks. These could promote, maintain or block transcriptional processes that, in turn, participate in the molecular adaptations underlying behavioral changes. Accordingly, epigenetics has become a central topic in several domains of neuroscience, including neurobiological approaches to drug addiction. In this chapter we summarize current evidence for the involvement of epigenetic mechanisms in the promotion of drug consumption and addictive behavior. We also suggest how the same epigenetic mechanisms could be used to improve the clinical management of these disorders.

Epigenetic processes play a central role in regulating the tissue-specific expression of genes. Alterations in these processes can therefore lead to profound changes in phenotype and have been implicated in the pathogenesis of many human diseases. However, there is now evidence that the epigenome is susceptible to a range of environmental cues such as variations in diet, maternal behaviour or stress during specific developmental periods. The environmental sensitivity of the epigenome has been suggested to reflect an adaptive mechanism, by which the organism can adjust its metabolism and homeostatic systems to suit the environment, in order to aid survival or reproductive success in later life. Inappropriate adaptation has been linked to the development of a range of chronic diseases in later life and has been suggested to account for at least some of the rapid increases in the rates of obesity, type II diabetes and cardiovascular disease recently observed in both developed and developing countries. This chapter will therefore focus on how nutritional cues in the environment can alter the epigenome, producing different phenotypes and altered disease susceptibilities from a single genotype.

Epigenetics explores heritable changes in gene expression that occur without changes in DNA sequence. Several epigenetic mechanisms - among which DNA methylation, histone modifications and microRNA expression are the best studied - can adapt genome function to respond to environmental requirements. In this chapter, we review current evidences indicating that environmental agents are able to modify epigenetic markers. The epigenetic alterations induced by some exposures are the same as/or similar to epigenetic alterations found in patients with diseases. Several investigations have examined the relationship between exposure to environmental chemicals and epigenetics, and have identified toxicants that modify epigenetic states. Among these we will focus on exposure to particulate matter, heavy metals and organic compounds. We have also considered how the length of the exposure and the concentration of pollutants may modify the environment-epigenome interaction, and how genetic variability, prenatal exposure, and circadian rhythm may mitigate or overstate epigenetic disruptions.