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).
|Experiment #||Strain||Median Lifespan||Sample Size||P (Tetx vs. Control)||Automated?|
|1||Tetx in ASI||17||66||0.0125||no|
|2||Tetx in ASI||16.9||118||<0.0001||yes|
|3||Tetx in ASI||15.9||141||<0.0001||yes|
|4||Tetx in ASI||16.3||156||0.0471||yes|
|5||Tetx in ASI||23||98||0.0025||no|
MethodsRequest 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).
CF4126: muEx641[pPC30(pgpa-4::GFP::Tetx) + punc-122::RFP]
NIH R01 AG011816
Reviewed ByJoy Alcedo
HistoryReceived: May 24, 2018
Accepted: June 1, 2018
Published: June 1, 2018