A research study on nematodes shows that odor aversion activates an action that could extend their life-span and provides insights into possible treatments for human neurodegenerative diseases. Credit: SciTechDaily
In a research study involving nematode worms, scientists found that when these worms were exposed to a particular compound released by hazardous bacteria, it triggered the activation of a neural pathway. This activation caused an increase in the life-span of the worms and a reduction in protein aggregation, which is understood to be a contributing factor in the development of neurodegenerative diseases.
An organisms response to repugnant odors can be a sign of the organisms capacity to protect itself from hazardous compounds and live longer. This at least is what takes place when it comes to nematodes of the types Caenorhabditis elegans.
Although nematodes (roundworms or threadworms) do not look remotely like humans, for about 50 years they have been utilized as a design for biological studies. The benefits consist of an easy nerve system, couple of cells and genes, a lot of which have the same functions as our own, and a brief lifespan averaging 17 days, which is ideal for research study on aging.
An article published in the journal Nature Aging reports the findings of a research study showing that odorant particles secreted by pathogenic germs not only produced an aversive reaction in C. elegans, which pulled away to avoid the threat but likewise activated a neural circuit that induced a response in other tissues of the nematode.
This reaction includes more efficient processing of hazardous proteins and control of the aggregation of these and other proteins produced by the worms. The relevance of this is that in people an accumulation of these proteins is among the aspects associated with neurodegenerative diseases such as Alzheimers and Parkinsons.
The red spots in this picture of the nematode C. elegans are a pair of nerve cells with the UPRER pathway triggered in action to the odorant molecule 1-undecene. Credit: Evandro de Souza & & Max Thompson
” They can notice danger in the environment by odor, heightening their stress actions even before they locate any pathogenic bacteria. Smell also prevents aggregation of proteins involved in illness, potentially extending their lifespan,” stated Evandro Araújo de Souza, very first author of the short article. The research study belonged to his postdoctoral research at the Neurobiology Division of the Medical Research Council Laboratory of Molecular Biology (MRC-LMB) in Cambridge in the United Kingdom.
Souza is among 32 researchers selected for FAPESPs Project Generation, which supports research study based on vibrant concepts conducted by early-career researchers with exceptional capacity. In September, he embarked on the next phase of the research study at the State University of Campinass Institute of Biology (IB-UNICAMP) in Brazil, where he will conduct the task ” Mechanisms of regulation of proteostasis in peripheral tissues by the worried system”..
Scenting threat.
In the study, nematodes exposed to 1-undecene, an odorant particle, lived longer than those that had no contact with the smell secreted by germs. Actions to the stimulus could be seen in the intestine, evidencing the presence of a circuit connecting olfactory understanding to the rest of the body..
” These findings recommend that controling understandings of chemical compounds might one day be a route to intervention in neurodegenerative and age-related diseases. More research is required to develop whether comparable cell signaling pathways and mechanisms likewise operate in people,” said Rebecca Taylor, a researcher at MRC-LMB and last author of the short article.
According to the researchers, other research studies had actually already revealed that mice have a neural circuit linking the brain to the liver when these animals smell particular type of food, and it makes good sense to assume that the mammalian nerve system could trigger an action by other organs when stimulated, as is the case in nematodes. “If we find a molecule that can mediate this circuit connecting the understanding of smell to the organisms reaction, we could have a promising route to establish novel treatments,” Souza stated.
Partially revealed circuit.
In the research study, the nematodes were put on various plates from those including the odorants to show that it was not direct contact between the worms and the compounds that triggered aversion however only their smell.
The odorants used were those produced by pathogenic germs such as Pseudomonas aeruginosa and Staphylococcus aureus, which are harmful to nematodes. Three of these substances including 1-undecene were connected with aversive responses in C. elegans. The scientists chose to concentrate on 1-undecene in subsequent experiments as it induced hostility without being toxic..
When they examined the worms exposed to the substance, they observed activation of the endoplasmic reticulum unfolded protein reaction (UPRER) in the intestine. This is a defense the organism uses to trigger repair work systems or get rid of faulty proteins.
In worms with anomalies in two genes that manage the UPRER ( ire-1 and xbp-1), the response was not activated by 1-undecene, showing that this cellular signaling path was necessary to the activation of UPRER by the substance. Other experiments validated this outcome.
Another group of mutant nematodes exposed to 1-undecene failed to produce neurotransmitters such as serotonin, dopamine, and glutamate, amongst others, however the scientists were not able to recognize a role for any of these particles..
Next, they concentrated on DAF-7, a protein and gene equivalent to transforming development factor-beta (TGF-β) in mammals, where it plays an essential role in the neural circuits that govern habits such as aversion to pathogens.
When production of DAF-7 was prevented, odorant-induced UPRER was not triggered, evidencing its function in this action. “We now understand the path we need to follow, specifically due to the fact that the protein has a comparable in human beings,” Souza said.
Recommendation: “Olfactory chemosensation extends lifespan through TGF-β signaling and UPR activation” by Evandro A. De-Souza, Maximillian A. Thompson and Rebecca C. Taylor, 27 July 2023, Nature Aging.DOI: 10.1038/ s43587-023-00467-1.
The research study was funded by the São Paulo Research Foundation..
” They can notice threat in the environment by odor, heightening their stress reactions even before they locate any pathogenic germs. The research study was part of his postdoctoral research at the Neurobiology Division of the Medical Research Council Laboratory of Molecular Biology (MRC-LMB) in Cambridge in the United Kingdom.