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microPublication / Biology / Silencing the ASI gustatory neuron...
Silencing the ASI gustatory neuron pair extends lifespan
Peter Chisnell1 and Cynthia Kenyon1
1Department of Biochemistry & Biophysics, University of California, San Francisco, San Francisco, CA 94143-2200, USA
Correspondence to: Peter Chisnell (peter.chisnell@ucsf.edu)

Description

Disrupting the function of sensory neurons of C. elegans can increase their lifespan (Apeld and Kenyon 1999). This effect is not limited to large-scale disruption, as ablation of single pairs of neurons have been shown to modify lifespan (Alcedo and Kenyon 2004; Lee and Kenyon 2009; Liu and Cai 2013). We tested whether silencing the neuron pair ASI with the tetanus toxin light chain (Tetx), as opposed to ablating it, could increase lifespan. Tetanus toxin disrupts neurotransmission by blocking the release of both small clear-core vesicles and large dense-core vesicles, but should not affect communication via gap junctions (Schiavo et al. 1992; McMahon et al. 1992). We expressed GFP::Tetx using the ASI-specific promoter pgpa-4 (Figure Panel A) and conducted lifespan assays comparing animals with high fluorescence and undetectable fluorescence. Tetx in ASI extended lifespan in otherwise wild-type animals (Figure Panel B, Table 1, 14.9% average median lifespan increase across 5 replicates).

Table 1

Experiment # Strain Median Lifespan Sample Size P (Tetx vs. Control) Automated?
1 Tetx in ASI 17 66 0.0125 no
Control 15 55
2 Tetx in ASI 16.9 118 <0.0001 yes
Control 14.4 110
3 Tetx in ASI 15.9 141 <0.0001 yes
Control 13.4 93
4 Tetx in ASI 16.3 156 0.0471 yes
Control 14.1 86
5 Tetx in ASI 23 98 0.0025 no
Control 21 68

Methods

Request a detailed protocol

Lifespan assays were conducted as previously described (Apfeld and Kenyon 1999) by hand with no FUDR, as well as utilizing automated lifespan machines (Stroustrup et al. 2013).

Reagents

Strains:
CF4126: muEx641[pPC30(pgpa-4::GFP::Tetx) + punc-122::RFP]

References

Alcedo, J., and Kenyon, C. (2004). Regulation of C. elegans Longevity by Specific Gustatory and Olfactory Neurons. Neuron 41, 45–55.
PubMed
Apfeld, J., and Kenyon, C. (1999). Regulation of lifespan by sensory perception in Caenorhabditis elegans. Nature 402, 804–809.
PubMed
Lee, S.-J., and Kenyon, C. (2009). Regulation of the Longevity Response to Temperature by Thermosensory Neurons in Caenorhabditis elegans. Curr Biol 19, 715–722.
PubMed
Liu, T., and Cai, D. (2013). Counterbalance between BAG and URX neurons via guanylate cyclases controls lifespan homeostasis in C. elegans. EMBO J 32, 1529–1542.
PubMed
McMahon, H.T., Foran, P., Dolly, J.O., Verhage, M., Wiegant, V.M., and Nicholls, D.G. (1992). Tetanus toxin and botulinum toxins type A and B inhibit glutamate, gamma-aminobutyric acid, aspartate, and met-enkephalin release from synaptosomes. Clues to the locus of action. J. Biol. Chem. 267, 21338–21343.
PubMed
Schiavo, G.G., Benfenati, F., Poulain, B., Rossetto, O., Laureto, P.P. de, DasGupta, B.R., and Montecucco, C. (1992). Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin. Nature 359, 832–835.
PubMed
Stroustrup, N., Ulmschneider, B.E., Nash, Z.M., Lopez-Moyado, I.F., Apfeld, J., and Fontana, W. (2013). The C. elegans Lifespan Machine. Nat Methods 10, 665–670.
10.1038/nmeth.2475 | PubMed

Funding

NIH R01 AG011816

Reviewed By

Joy Alcedo

History

Received: May 24, 2018
Accepted: June 1, 2018
Published: June 1, 2018

Copyright

© 2018 by the authors. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Citation

Chisnell, P; Kenyon, C (2018). Silencing the ASI gustatory neuron pair extends lifespan. microPublication Biology. 10.17912/ft9e-7e37.
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