Editor's Choice: A study in nematodes suggests that odor aversion triggers a response that may prolong the lifespan of nematodes and provide insight into the potential for neurodegenerative diseases in humans.In a study involving nematodes, scientists found that when these nematodes were exposed to specific compounds released by harmful bacteria, it triggered the activation of neural pathways. This activation leads to an increase in the lifespan of nematodes and a decrease in protein aggregation, which is a contributing factor in the development of known neurodegenerative diseases.
An organism's response to unpleasant odors can serve as an indicator of the organism's ability to protect itself from harmful substances and the increase in its lifespan. This is at least the case of Caenorhabditis elegans.
Although nematodes don't look like humans at all, they have been used as a model for biological research for about 50 years. Its advantages include a simple nervous system, few cells and genes, many of which function the same as our own, and a very short average lifespan of only 17 days, which is ideal for studying aging.
An article published in the journal Nature Aging reports the results of a study that showed that odor molecules secreted by pathogenic bacteria not only create an aversion response in Caenorhabditis elegans, causing it to flinch to avoid threats, but also trigger neural circuits that induce other tissues in C. elegans to react.
This reaction involves more efficient processing of toxic proteins and controlling the aggregation of these proteins and other proteins produced by nematodes. Related to this, in humans, the accumulation of these proteins is one of the factors associated with neurodegenerative diseases such as Alzheimer's and Parkinson's.
They can sense danger in their environment through their sense of smell and enhance their stress response even before they find any pathogenic bacteria. Odor also prevents the aggregation of disease-related proteins, potentially extending their lifespan. Evandro Araújo de Souza, the first author of the article, said the study was part of his postdoctoral research in the neurobiology unit of the Laboratory of Molecular Biology (MRC-LMB) of the Medical Research Council in Cambridge, UK.
Souza is one of 32 scientists selected for the Fapesp Generation Project, which supports research based on bold ideas by early-career researchers with outstanding potential. In September, he began the next phase of his research at the Institute of Biology of the State University of Campinas (IB-UNICAMP) in Brazil, where he will lead the project "Mechanisms of Nervous System Regulation of Protein Arrest in Peripheral Tissues".
In this study, nematodes exposed to 1-undecyne (an odor molecule) lived longer than those who were not exposed to odors secreted by bacteria. The response to stimuli can be seen in the gut, proving the existence of a circuit that connects olfactory perception with the rest of the body.
These findings suggest that manipulating the perception of chemicals could one day be a pathway to intervene in neurodegenerative and age-related diseases. However, more research is needed to determine whether similar cell signaling pathways and mechanisms also play a role in humans. Rebecca Taylor, an MRC-LMB researcher and the final author of the article, said.
According to the researchers, other studies have shown that when mice smell a certain food, there is a neural circuit between their brain and liver, so it makes sense to assume that the mammalian nervous system can trigger a response from other organs when stimulated, as is the case with nematodes. "If we find a molecule that can modulate this loop that connects odor perception and the response of organisms, we have the potential to develop a new approach," Souza said. ”
In this study, nematodes were placed on different plates, rather than on plates containing odorants, to demonstrate that there was not direct contact between nematodes and the substances that cause disgust, but rather direct contact with their odor.
The odorants used are secreted by pathogenic bacteria that are harmful to nematodes, such as Pseudomonas aeruginosa and Staphylococcus aureus. Three of these compounds, including 1-undecyne, have been implicated in the aversive response of Caenorhabditis elegans. The researchers decided to focus on 1-undecane in subsequent experiments because it caused disgust in the absence of toxicity.
When they analyzed nematodes exposed to the substance, they observed the activation of the intestinal endoplasmic reticulum unfolded protein response (UPRER). This is a defense that the body uses to trigger repair mechanisms or eliminate defective proteins.
In nematodes with mutations in two genes that regulate uprer (ire-1 and xbp-1), this response was not activated by 1-undecadene, suggesting that this cell signaling pathway is critical for this substance to activate uprer. Other experiments have confirmed this result.
Another group of mutant nematodes exposed to 1-undecyne were unable to produce neurotransmitters such as serotonin, dopamine, and glutamate, among others, but the researchers were unable to determine the role of these molecules.
Next, they focused on DAF-7, a protein and gene equivalent to transforming growth factor (TGF-) in mammals, which plays an important role in neural circuits that control behaviors such as pathogen aversion.
When DAF-7 production is inhibited, odor-induced uprer is not activated, demonstrating its role in this response. "We now know the route we need to follow, especially since this protein is in equal amounts in humans," Souza said. ”
*：nature aging
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