Abstract 2082 Understanding the Role of RNA Polymerase I in Regulating Longevity of Caenorhabditis elegans

Ribosome biogenesis is an essential process that has been shown to play a role in regulating the health and lifespan of an organism. Reduced ribosome biogenesis, in conjunction with reduced nucleolar size has been linked to an increase in lifespan. RNA Polymerase (Pol) I is responsible for the transcription of pre-ribosomal RNA (rRNA), an integral process in ribosome assembly. The demand for ribosomes means that Pol I accounts for a large fraction of all transcription activity in a cell. In this study, a genomically altered lab-grown strain of Caenorhabditis elegans with an auxin-responsive degron tag for Pol I subunit A was utilized to observe lifespan changes in C. elegans when Pol I expression is partially reduced globally and tissue specifically. Global partial reduction of Pol I expression is sufficient in extending the lifespan of C. elegans. Moreover, partial reduction in Pol I in the hypodermis, body wall muscle, pharyngeal muscle, intestine and germline are respectively sufficient to significantly extend lifespan. These results show that our system could provide insight into tissue-specific contribution in Pol I-mediated longevity and suggest the presence of a cell non-autonomous regulation.