The mitochondria are inextricably linked to the process of aging. Whether through the release of reactive oxygen species (ROS), peptidergic signals or otherwise, mitochondrial signaling can potently enhance lifespan and health in a multitude of species. Despite the mitochondria’s apparent and central role in modulating aging, many open questions remain on the subject of how this signaling exactly occurs. For example, many nodes in the mitochondrial ROS signaling network remain unidentified. Even more notable is the lack of knowledge concerning mitochondrial peptidergic signaling, as the peptides involved are encoded in small non-canonical coding sequences, thus originally excluded from gene searches. However, recent
findings have shown that these small mitochondrial peptides represent an almost wholly unexplored source of potential aging mediators. Here, we will employ the small nematode Caenorhabditis elegans, one of the most popular model organisms for aging research, to build a functional framework for mitochondrial regulation of healthy aging, with a focus on signaling through peroxiredoxins and small peptides. To accomplish this, we will employ a variety of molecular, bioinformatics and functional phenotyping techniques to assay various aspects of this framework. Together, this will improve our fundamental knowledge of how mitochondrial signaling affects aging, while simultaneously exploring the burgeoning field of small mitochondrial peptides.