Neuronal expression of bromodomain proteins alter neuronal health and peripheral protein homeostasis to promote longevity
Longevity and stress resilience require coordinated gene expression across tissues. We found that neuronal overexpression of the chromatin reader BET-1 in C. elegans extends lifespan and enhances stress resistance through cell non-autonomous signaling. Neuronal BET-1 triggers a neurotransmitter-dependent activation of the conserved transcription factor HSF-1 in the intestine, promoting proteostasis, oxidative stress resistance, and immune defense. To uncover the molecular mechanisms underlying this systemic response, we performed bulk RNA sequencing, which revealed coordinated activation of gene networks involved in heat-shock response, proteostasis, and pathogen resistance. These transcriptomic signatures define the downstream effectors of neuronal BET-1 and highlight distinct regulatory mechanisms mediated by hsf-1 and daf-16. Together, these findings establish BET-1 as a key regulator of inter-tissue communication and demonstrate the critical role of RNA-seq in identifying the transcriptional programs that couple neuronal signaling to organismal longevity and resilience.
Longevity and stress resilience require coordinated gene expression across tissues. We found that neuronal overexpression of the chromatin reader BET-1 in C. elegans extends lifespan and enhances stress resistance through cell non-autonomous signaling. Neuronal BET-1 triggers a neurotransmitter-dependent activation of the conserved transcription factor HSF-1 in the intestine, promoting proteostasis, oxidative stress resistance, and immune defense. To uncover the molecular mechanisms underlying this systemic response, we performed bulk RNA sequencing, which revealed coordinated activation of gene networks involved in heat-shock response, proteostasis, and pathogen resistance. These transcriptomic signatures define the downstream effectors of neuronal BET-1 and highlight distinct regulatory mechanisms mediated by hsf-1 and daf-16. Together, these findings establish BET-1 as a key regulator of inter-tissue communication and demonstrate the critical role of RNA-seq in identifying the transcriptional programs that couple neuronal signaling to organismal longevity and resilience.