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Abstract Mitochondrial stress within the nervous system can trigger non-cell autonomous responses in peripheral tissues. However, the specific neurons involved and their impact on organismal aging and health have remained incompletely understood. Here, we demonstrate that mitochondrial stress in γ-aminobutyric acid-producing (GABAergic) neurons inCaenorhabditis elegans(C. elegans) is sufficient to significantly alter organismal lifespan, stress tolerance, and reproductive capabilities. This mitochondrial stress also leads to significant changes in mitochondrial mass, energy production, and levels of reactive oxygen species (ROS). DAF-16/FoxO activity is enhanced by GABAergic neuronal mitochondrial stress and mediates the induction of these non-cell-autonomous effects. Moreover, our findings indicate that GABA signaling operates within the same pathway as mitochondrial stress in GABAergic neurons, resulting in non-cell-autonomous alterations in organismal stress tolerance and longevity. In summary, these data suggest the crucial role of GABAergic neurons in detecting mitochondrial stress and orchestrating non-cell-autonomous changes throughout the organism.
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This content will become publicly available on April 24, 2026
Amyloid β induces hormetic-like effects through major stress pathways in a C. elegans model of Alzheimer’s Disease
Amyloid β (Aβ) is a peptide known for its characteristic aggregates in Alzheimer’s Disease and its ability to induce a wide range of detrimental effects in various model systems. However, Aβ has also been shown to induce some beneficial effects, such as antimicrobial properties against pathogens. In this work, we explore the influence of Aβ in stress resistance in aC. elegansmodel of Alzheimer’s Disease. We found thatC. elegansthat express human Aβ exhibit increased resistance to heat and anoxia, but not to oxidative stress. This beneficial effect of Aβ was driven from Aβ in neurons, where the level of induction of Aβ expression correlated with stress resistance levels. Transcriptomic analysis revealed that this selective stress resistance was mediated by the Heat Shock Protein (HSPs) family of genes. Furthermore, neuropeptide signaling was necessary for Aβ to induce stress resistance, suggesting neuroendocrine signaling plays a major role in activating organismal stress response pathways. These results highlight the potential beneficial role of Aβ in cellular function, as well as its complex effects on cellular and organismal physiology that must be considered when usingC. elegansas a model for Alzheimer’s Disease.
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- Award ID(s):
- 2039226
- PAR ID:
- 10631037
- Editor(s):
- Tavernarakis, Nektarios
- Publisher / Repository:
- PLOS One
- Date Published:
- Journal Name:
- PLOS One
- Volume:
- 20
- Issue:
- 4
- ISSN:
- 1932-6203
- Page Range / eLocation ID:
- e0315810
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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