Neurodegeneration and neuromuscular disease both seem to be correlates of aging. These pathological processes are thought to result, at least in part, from the chronic accumulation of reactive oxygen species (ROS) generated through normal cellular metabolism.
A recent report from Kishi et al. demonstrates the utility of zebrafish in the identification of genes that regulate oxidative stress and aging in vertebrates. Using both N-ethyl-N-nitrosourea (ENU) mutagenesis and retroviral insertion methods to induce genetic mutations in zebrafish embryos, they identified genes that alter the expression of a senescence-associated β-galactosidase under conditions of oxidative stress. Their study shows that biomarkers of stress response in embryos are consistent with degeneration and advanced aging phenotypes in adults since many of the genes identified in the screen also induce aging-related phenotypes in adult zebrafish. Two genes identified in this screen included homologs for Drosophila spinster, which regulates neurodegeneration and lifespan in flies, and human TERF2, which produces a telomere-nucleoprotein complex protein that is important in telomere regulation. This work demonstrates the potential for zebrafish as a tractable vertebrate model for identification of aging-related genes.
