EOR-1 as mediator of life- and health-promoting EGF signaling

Abstract

Royalactin is a glycoprotein essential for the development of long-lived queen honeybees. We recently provided the first evidence for its longevity-promoting actions in a non-insect species by studying royalactin-fed C. elegans (Detienne et al., Experimental Gerontology 2015). We demonstrated that royalactin requires both Epidermal Growth Factor (EGF, LIN-3) and its receptor (LET-23) for extension of C. elegans lifespan by ~25%. Royalactin also enhanced stress tolerance and locomotion in adult nematodes, suggesting a positive effect on healthspan as well. Yet, the mechanism by which royalactin exerts these EGF-mediated effects remained largely unknown. Our work now reveals that EGF signaling is capable of SKN-1-independent transcriptional activation of glutathione S-transferase 4 (GST-4). For this it relies on the transcription factor EOR-1, which is needed for both the life- and the health-promoting effects of royalactin. While reproductive capacity remains unaltered upon royalactin treatment, additional molecular effectors emerging from differential proteomics analyses suggest that autophagy and/or translation are affected in royalactin-fed animals. These data help clarify the relations between EGF signaling, lifespan, health, stress tolerance, and reproduction in aging C. elegans.status: publishe