summary: Nematodes of the Caenorhabditis elegans species exhibit an aversion to noxious odors, which may be an indicator of increased longevity of the nematodes.
New research reveals that these odor molecules from pathogens not only trigger avoidance behavior in nematodes, but also stimulate protective neural circuits in other tissues. This circuit facilitates efficient processing of toxic proteins similar to those associated with human neurodegenerative diseases.
This study suggests that sensing environmental danger through smell may be an evolutionary mechanism for extending lifespan.
Important facts:
- Exposure to the odor molecule 1-undecene was demonstrated to extend the lifespan of C. elegans and improve protein processing in the intestine.
- Activation of the endoplasmic reticulum unfolded protein response (UPRER) in the C. elegans intestine plays an important role in the processing of toxic proteins upon exposure to odorants.
- The protein DAF-7 corresponds to TGF-β in humans and is essential for aversive responses and may provide insight into human studies.
sauce: FAPESP
Aversion to unpleasant odors may be an indicator of an organism’s ability to protect itself from harmful substances and live longer.This is at least what happens with this type of nematode. Caenorhabditis elegans.
Although nematodes (roundworms or heartworms) bear little resemblance to humans, they have been used as a model for biological research for about 50 years. Their advantages include a simple nervous system, a small number of cells and genes, many of which have the same functions as us, and a short lifespan of 17 days on average, making them ideal for research on aging. I can list it.
Article published in magazine natural aging report on research showing that odor molecules secreted by pathogenic bacteria do more than just cause discomfort. C.Eleganceretreated to avoid the threat, but also triggered neural circuits and reactions in other tissues of the worm.
This response includes more efficient processing of toxic proteins and control of aggregation of these and other proteins produced by the nematode. Of relevance is that in humans, accumulation of these proteins is one of the factors associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease.
“They use smell to detect environmental dangers and heighten stress responses before they find pathogens. Smell also prevents disease-related protein aggregation and may extend the lifespan of proteins.” said Evandro Araujo de Sousa, lead author of the paper.
The study was part of postdoctoral research in the Department of Neurobiology at the Medical Research Council Laboratory of Molecular Biology (MRC-LMB) in Cambridge, UK.
Souza is one of 32 scientists selected for FAPESP’s Project Generation, which supports research based on bold ideas by young researchers with great potential. In September, he embarked on the next stage of his research at the Biological Institute of the State University of Campinas (IB-UNICAMP) in Brazil, where he carried out the project “Mechanisms of control of proteostasis in peripheral tissues by the nervous system” It is expected to be.
The danger of fragrance
In this study, worms exposed to the odor molecule 1-undecene survived longer than those that were not exposed to the odor secreted by the bacteria. Responses to stimuli were seen in the intestines, proving the existence of circuits that connect the sense of smell to other parts of the body.
“These findings suggest that manipulating chemical recognition may one day be a means to intervene in neurodegenerative and age-related diseases. However, similar cellular signaling pathways Further research is needed to establish whether the mechanism also works in humans,” said Rebecca Taylor, a researcher at MRC-LMB and final author of the paper.
According to the researchers, other studies have already shown that when mice smell certain types of food, there is a neural circuit connecting the brain and liver, and when the mammal’s nervous system is stimulated, The hypothesis that it could trigger a reaction by other organs makes sense. The same is true for nematodes.
“Discovering molecules that can mediate this circuit that links odor perception and biological responses could open a promising avenue for developing new treatments,” Souza said.
Partially exposed circuit
The study placed the worms on a separate plate from the one containing the odorant and demonstrated that the odor alone, rather than direct contact between the worm and the substance that caused the aversion, was responsible.
The odorants used were those secreted by pathogenic bacteria such as: Pseudomonas aeruginosa and Staphylococcus aureus, harmful to nematodes. Three of these compounds, including 1-undecene, were associated with aversive responses in humans. C.Elegance. The researchers decided to focus on 1-undecene in subsequent experiments because it is not toxic and induces disgust.
When we analyzed C. elegans exposed to this substance, we observed activation of the endoplasmic reticulum unfolded protein response (UPR).E.R.) in the intestine. This is a defense that organisms use to trigger repair mechanisms or eliminate defective proteins.
In the case of nematodes with mutations in two genes that control the UPRE.R. (ire-1 and xbp-1), the response was not activated by 1-undecene, indicating that this cellular signaling pathway is essential for UPR activation.E.R. By matter. Other experiments confirmed this result.
Another group of mutant worms exposed to 1-undecene specifically failed to produce neurotransmitters such as serotonin, dopamine, and glutamate, but the researchers were unable to determine the role of these molecules.
Next, they focused on DAF-7, a protein and gene that corresponds to mammalian transforming growth factor beta (TGF-β). DAF-7 plays an important role in neural circuits that control behaviors such as aversion to pathogens.
Inhibition of DAF-7 production causes odorant-induced UPRE.R. is not activated, demonstrating a role in this reaction. “We now know the path to follow, especially since this protein has a human equivalent,” Souza said.
About this longevity research news
author: Eloisa Reinert
sauce: FAPESP
contact: Eloisa Reinert – FAPESP
image: Image credited to Neuroscience News
Original research: Open access.
“Olfactory chemosensation extends lifespan through TGF-β signaling and UPR activationWritten by Evandro Araujo de Sousa et al. natural aging
abstract
Olfactory chemosensation extends lifespan through TGF-β signaling and UPR activation
Animals rely on chemosensory cues to survive in pathogen-rich environments.in Caenorhabditis elegans, pathogenic bacteria induce aversive behavior through neural perception and activate molecular defenses throughout the animal. This suggests that neurons can coordinate the activation of defense responses throughout the organism upon recognition of pathogens.
In this study, we found that exposure to volatile pathogen-associated compounds induces activation of the endoplasmic reticulum unfolded protein response (UPR).E.R.) in peripheral tissues after xbp-1 Neuron splicing.
UPR caused by this odorantE.R. Activation is dependent on DAF-7/transforming growth factor beta (TGF-β) signaling, leading to increased lifespan and enhanced clearance of toxic proteins.Notably, rescue of DAF-1 TGF-β receptors in RIM/RIC interneurons is sufficient to significantly restore the UPRE.R. Activates upon exposure to 1-undecene.
Our data suggest a cell-nonautonomous UPR.E.R. Rewiring the organism’s proteostasis in response to pathogen detection and preempting proteotoxic stress. Therefore, chemosensitivity to specific odors may provide a means to manipulate stress responses and lifespan.
