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Updated: Oct 21, 2026
Quantifying Levels of Dopaminergic Neuron Morphological Alteration and Degeneration in Caenorhabditis elegans
Published on: November 20, 2021
Cell-intrinsic mTOR/LET-363 influences morphological aging of the ALM touch receptor neuron in Caenorhabditis elegans
Sophia C Whitley1, Ruiling Zhong1, Sophie Baumberger1
1Department of Genetics, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Abstract:
The mechanistic target of rapamycin (mTOR) promotes neuronal aging, but it remains unclear whether these effects arise from mTOR activity within neurons, other brain cell types, or peripheral tissues. Here, we tested the hypothesis that Caenorhabditis elegans mTOR/let-363 functions cell-intrinsically in neurons during adulthood to promote age-related neuron morphological aging. We used a floxed let-363 allele in combination with heat-shock-induced, pan-somatic Cre recombinase expression to generate pan-somatic, adult knockdown, and with a Cre-driver that expresses in a small subset of neurons, the Touch Receptor Neurons, to generate neuron-intrinsic knockdown. Adult-onset, pan-somatic knockdown of let-363 did not robustly alter lifespan or neuron morphological aging. In contrast, neuron-specific let-363 knockdown resulted in a reduction in one aspect of neuron morphological aging - ectopic neurite sprouting from the soma - without extending lifespan. Together, these findings suggest that mTOR/let-363 can act cell-intrinsically within neurons to promote or potentiate an aspect of morphological aging. These results help clarify the potential cell-type specificity of mTOR's roles in neuronal aging and provide a foundation for defining the mechanisms through which mTOR intersects with neuron-intrinsic aging pathways.
Insights
Mechanistic target of rapamycin (mTOR) promotes neuronal aging. Neuron-specific knockdown of mTOR/let-363 in adult worms reduced ectopic neurite sprouting, clarifying its cell-intrinsic role in neuron aging.
Area of Science:
- Neuroscience
- Aging Research
- Molecular Biology
Background:
- The mechanistic target of rapamycin (mTOR) pathway is implicated in aging processes.
- Its specific role and cell-type dependency in neuronal aging remain largely undefined.
- Understanding mTOR's cell-intrinsic functions is crucial for targeting age-related neurological decline.
Purpose of the Study:
- To investigate whether Caenorhabditis elegans mTOR/let-363 functions cell-intrinsically within neurons to drive age-related morphological aging.
- To determine the cell-type specificity of mTOR's contribution to neuronal aging.
Main Methods:
- Utilized a floxed let-363 allele with heat-shock-induced Cre recombinase for inducible knockdown.
- Generated pan-somatic and neuron-specific (Touch Receptor Neurons) let-363 knockdown models in adult C. elegans.
- Assessed lifespan and neuron morphological aging, including ectopic neurite sprouting.
Main Results:
- Adult-onset, pan-somatic knockdown of let-363 did not significantly affect lifespan or overall neuron morphological aging.
- Neuron-specific knockdown of let-363 reduced ectopic neurite sprouting from the neuronal soma.
- Lifespan was not extended by neuron-specific let-363 knockdown.
Conclusions:
- mTOR/let-363 signaling can act cell-intrinsically within neurons to promote specific aspects of morphological aging.
- These findings highlight the cell-type specificity of mTOR's roles in neuronal aging.
- Provides a basis for further research into mTOR's interaction with neuron-intrinsic aging pathways.
