Age‐dependent heat shock hormesis to HSF‐1 deficiency suggests a compensatory mechanism mediated by the unfolded protein response and innate immunity in young Caenorhabditis elegans

Aging Cell, Journal Year: 2024, Volume and Issue: 23(10)

Published: June 19, 2024

Abstract The transcription factor HSF‐1 (heat shock 1) acts as a master regulator of heat response in eukaryotic cells to maintain cellular proteostasis. protein has protective role preventing from undergoing ageing, and neurodegeneration, also mediates tumorigenesis. Thus, modulating activity humans promising therapeutic potential for treating these pathologies. Loss function is usually associated with impaired stress tolerance. Contrary this conventional knowledge, we show here that inactivation the nematode Caenorhabditis elegans results increased thermotolerance at young adult stages, whereas deficiency animals passing early stages indeed leads decreased thermotolerance, compared wild‐type. Furthermore, gene expression analysis supports adults, distinct immunity‐related signaling pathways become induced upon deficiency. We demonstrate tolerance proteotoxic HSF‐1‐depleted worms requires unfolded endoplasmic reticulum SKN‐1/Nrf2‐mediated oxidative pathway, well an innate suggesting mutual compensatory interaction between conserved systems. A similar molecular network likely operate higher animal taxa, raising possibility unexpected outcome when manipulated humans.

Language: Английский

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The neurohormone tyramine stimulates the secretion of an insulin-like peptide from the Caenorhabditis elegans intestine to modulate the systemic stress response

PLoS Biology, Journal Year: 2025, Volume and Issue: 23(1), P. e3002997 - e3002997

Published: Jan. 28, 2025

The DAF-2/insulin/insulin-like growth factor signaling (IIS) pathway plays an evolutionarily conserved role in regulating reproductive development, life span, and stress resistance. In Caenorhabditis elegans , DAF-2/IIS is modulated by extensive array of insulin-like peptides (ILPs) with diverse spatial temporal expression patterns. However, the release dynamics specific functions these ILPs adapting to different environmental conditions remain poorly understood. Here, we show that ILP, insulin-3 (INS-3), a crucial modulating response various stressors C. . ins-3 mutants display increased resistance heat, oxidative stress, starvation; however, this advantage countered slower development under favorable conditions. We find downregulated stressors, whereas, neurohormone tyramine, which released during acute flight response, increases expression. tyramine induces intestinal calcium (Ca 2+ ) transients through activation TYRA-3 receptor. Our data support model negatively impacts stimulating INS-3 from intestine via TYRA-3-G α q -IP3 pathway. systemically activates DAF-2 pathway, resulting inhibition cytoprotective mechanisms mediated DAF-16/FOXO. These studies offer mechanistic insights into brain–gut communication weighs adaptive strategies respond long-term stressors.

Language: Английский

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Transcriptomic and chromatin accessibility profiling unveils new regulators of heat hormesis inCaenorhabditis elegans

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 14, 2025

Heat hormesis describes the beneficial adaptations from transient exposure to mild heat stress, which enhances stress resilience and promotes healthy aging. It is thought be underlying basis of popular wellness practices like sauna therapy. Despite extensive documentation across species, molecular long-term protective effects remain poorly understood. This study bridges that critical gap through a comprehensive multiomic analysis, providing key insights into transcriptomic chromatin accessibility landscapes throughout regimen adapted in C. elegans . We uncover highly dynamic dose-dependent responses reveal while most initial stress-induced changes revert baseline, differences response subsequent shock challenge are directly linked physiological benefits. identify new regulators hormesis, including MARS-1/MARS1, SNPC-4/SNAPc, ELT-2/GATA4, FOS-1/c-Fos, DPY-27/SMC4, likely orchestrate gene expression programs enhance distinct biological pathways. advances our understanding mechanisms, points multiple avenues future investigations, suggests potential strategies for promoting aging mid-life management.

Language: Английский

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A Ginsenoside Composition Ameliorated Aβ and Tau Aggregation via Autophagy Lysosome Pathway

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: May 6, 2025

Language: Английский

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Antiaging Effect of 2-O-β-D-Glucopyranosyl Ascorbic Acid Derived from Lycium barbarum L. Through Modulating the IIS Pathway and Gut Microbiota in Caenorhabditis elegans

Foods, Journal Year: 2025, Volume and Issue: 14(11), P. 1875 - 1875

Published: May 25, 2025

2-O-β-D-Glucopyranosyl ascorbic acid (AA-2βG), a bioactive derivative isolated from the fruits of Lycium barbarum L., exhibited significant antiaging effects in Caenorhabditis elegans. It significantly extended their lifespan, enhanced stress resistance, reduced lipofuscin accumulation, and improved healthspan, while strengthening antioxidant defenses. Transcriptomic analysis identified insulin/insulin-like growth factor (IGF)-1 signaling pathway as key regulator, with quantitative real-time polymerase chain reaction confirming upregulation longevity-associated genes. Functional studies showed that transcription factors DAF-16, HSF-1, SIR-2.1 were essential for lifespan-extending AA-2βG, mutations these genes abolished lifespan extension. Moreover, 16S rRNA sequencing revealed AA-2βG modulated gut microbiota by increasing taxa reducing pro-aging species, alterations linked to metabolic pathways. These findings suggest exerts through coordinated regulation IIS composition, highlighting its potential natural geroprotective compound.

Language: Английский

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