Language
English
Publication Date
8-26-2026
Journal
Genes & Development
DOI
10.1101/gad.353559.125
PMID
42562575
PMCID
PMC13532663
PubMedCentral® Posted Date
9-1-2026
PubMedCentral® Full Text Version
Post-print
Abstract
Longevity and stress resilience require precise coordination of gene expression programs across tissues. Here, we demonstrate that overexpression of the chromatin reader bet-1 specifically in neurons of Caenorhabditis elegans promotes organismal longevity and stress resistance via cell-nonautonomous signaling. Neuronal bet-1 elicits a neurotransmitter-dependent signal that activates the conserved stress-responsive transcription factor HSF-1 in the intestine, enhancing proteostasis, oxidative stress resistance, metabolic remodeling, and immune defense. Life span extension by neuronal bet-1 requires both hsf-1 and daf-16 in neurons but only requires hsf-1 in peripheral tissues. Using bulk RNA sequencing, we reveal distinct prolongevity pathways that include enhanced heat-shock response, proteostasis, increased actin stability, and resistance to pathogens, which likely together coordinate the prolongevity effects of neuronal bet-1. Our findings establish BET-1 as a potent nonautonomous regulator of aging and stress response, highlighting chromatin readers as upstream modulators of intertissue signaling and systemic resilience.
Keywords
Animals, Caenorhabditis elegans, Longevity, Caenorhabditis elegans Proteins, Neurons, Proteostasis, Signal Transduction, Transcription Factors, Gene Expression Regulation, Homeostasis, Bromodomain Containing Proteins, Forkhead Transcription Factors, Stress, Physiological
Published Open-Access
yes
Recommended Citation
Dutta, Naibedya; Hicks, Daniel; Esparza, Edgar; et al., "Neuronal Expression of Bromodomain Proteins Alters Neuronal Health and Peripheral Protein Homeostasis to Promote Longevity" (2026). Faculty, Staff and Students Publications. 7969.
https://digitalcommons.library.tmc.edu/baylor_docs/7969