Aging and epigenetics in Public Health

Aging is a multifactorial process involving a complex network of genetic and epigenetic regulations. The genetic component of aging received the most attention initially, and genome instability caused by telomere attrition and accumulation of mutations remains a leading cause of aging, accompanied by deteriorations in the repair of DNA damage. However, epigenetic mechanisms have now emerged as key contributors to aging. The pillars of epigenetic regulation include, but are not limited to, DNA methylation, histone modifications, chromatin structures, and non-coding RNAs. Alterations of these epigenetic mechanisms affect the vast majority of gene regulations in transcription and silencing, DNA replication and repair, cell-cycle progression, telomere metabolism, and centromere organization. In addition to genetic susceptibility, several lines of evidence indicate that epigenetic perturbations might represent a major factor in the pathophysiology of aging and age-associated diseases, including cancer. The pathological processes such disorders are thought to result, at least in part, from the chronic accumulation of reactive oxygen species (ROS) generated through normal cellular metabolism as well as caused from environments. Thus, both genetic background and epigenetic modulations are important determinants of the aging process and subsequently impact the process of chronic disease via a complex interplay of ‘gene-environment interactions'. Our recent study demonstrates the utility of zebrafish (Danio rerio) in the identification of genes that regulate oxidative stress and aging. Using large-scale mutagenesis approaches to induce genetic mutations in zebrafish, we identified a number of genes that alter the marker of “embryonic and/or larval senescence” under conditions of intrinsic and extrinsic stress challenges. The genes identified in the screen were also associated with actual aging phenotypes of animals, suggesting that adaptive stress responses in embryos are consistent with advanced aging symptoms in adults. Our works have demonstrated the potential of zebrafish as a tractable vertebrate model for identification of aging-related genes and epigenetic modifiers through their early developmental process in an unbiased fashion and high-throughput manner.