Sadie Katzenstein
Research Mentor(s): Scott Leiser
Mentor Department: Molecular and integrative Physiology
Authors: Sadie Katzenstein, Faith Carranza, Scott Leiser
Session: Session 4 (1:00pm – 1:50pm)
Presentation Type: Poster 71
Abstract
Aging is a decline in tissue function and integrity overtime, which is accompanied by an increased risk of developing chronic disease and morbidity. The population 65 years and older is rapidly growing, with a 38.6% increase in ten years—one of the fastest rates compared to any other decade. This growth underscores the importance of aging research and the identification of interventions that improve healthspan and lifespan. The field of geroscience has identified many ways to increase lifespan and healthspan in model organisms, raising the question of whether therapies can be designed to promote healthy aging in humans and decrease disease burden in the elderly population. C. elegans are valuable model organisms for studying aging due to their short life spans and extensive genetic malleability. fmo-2 is a pro-longevity gene that is sufficient to extend lifespan and healthspan when overexpressed (OE) in C. elegans. To better understand the molecular mechanisms by which FMO-2 OE promotes health benefits, we performed motif enrichment analysis of the promoters of differentially expressed genes in FMO-2 OE worms to identify novel transcription programs that may be driving longevity. We found enrichment of nuclear hormone receptor (NHR-6) binding sites among the promoters of differentially expressed genes. Therefore, we hypothesized that NHR-6 drives the longevity, stress resistance, and metabolic changes in FMO-2 OE worms. We found that nhr-6 mRNA levels are upregulated in FMO-2 OE worms. By knocking down nhr-6 in wild type (WT) and FMO-2 OE worms using RNAi and assessing lifespan, we found that nhr-6 is necessary to extend lifespan and decreasing fat storage in FMO-2 OE worms. Unexpectedly, we found that RNAi knockdown of nhr-6 is beneficial for stress resistance in WT worms. Our data suggest NHR-6 is active in FMO-2 OE worms and is a potential pro-longevity transcription factor. In future studies, we will assess if overexpression of nhr-6 is sufficient to promote longevity and increase healthspan, and test which genes are affected by increased NHR-6 activity in FMO-2 overexpressing worms.
