An Understudied Dimension: Why Age Needs to Be Considered When Studying Epigenetic-Environment Interactions

Abstract

We live in a complex chemical environment where there are an estimated 350 000 chemical compounds or mixtures commercially produced. A strong body of literature shows that there are time points during early development when an organism's epigenome is particularly sensitive to chemicals in its environment. What is less understood is how gene-environment and epigenetic-environment interactions change with age. This question is bidirectional: (1) how do chemicals in the environment affect the aging process and (2) how does aging affect an organism's response to its chemical environment? The study of gene-environment interactions with age is especially important because, in many parts of the world, older individuals are a large and rapidly growing proportion of the population and because aging is a process universal to most of the animal kingdom. Epigenetics has emerged as a crucial framework for studying aging as epigenetic pathways, often triggered by environmental stimuli, have been shown to be essential regulators of the aging process. In this perspective article, we delineate the connection between aging, epigenetics, and environmental exposures. We discuss why it is essential to consider age when researching how an organism interacts with its environment. We describe recent advances in understanding how the chemical environment affects aging and the gap in research on how age affects an organism's response to the environment. Finally, we highlight how model organisms and network approaches can help fill this crucial gap. Taken together, systemic changes that occur in the epigenome with age indicate that adult organisms cannot be treated as a homogeneous population and that there are discrete mechanisms modulating the aging epigenome that we do not yet understand.

Keywords: Biology of aging; environmental toxicology; epigenetics.

Figure 1.

The relationship between epigenetics and aging. Aging can be defined as an imbalance between stress and stress-buffering capacity. The chemical environment influences aging principally by increasing or decreasing the rate of epigenetic aging and/or by increasing the variation in epigenetic marks. What is largely unknown, however, is how aging affects an organism’s response to its chemical environment and what role the epigenome plays in that response. To understand how aging impacts epigenetic-environment interactions at the mechanistic level, network analysis and model organisms, such as Caenorhabditis elegans, should be leveraged.