Reduced <i>Ribose-5-Phosphate Isomerase A-1</i> Expression in Specific Neurons and Time Points Promotes Longevity in <i>Caenorhabditis elegans</i>
Deregulation of redox homeostasis is often associated with an accelerated aging process. Ribose-5-phosphate isomerase A (RPIA) mediates redox homeostasis in the pentose phosphate pathway (PPP). Our previous study demonstrated that <i>Rpi</i> knockdown boosts the healthspan in <i>Dr...
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| Main Authors: | , , , , , , |
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| Format: | Book |
| Published: |
MDPI AG,
2023-01-01T00:00:00Z.
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| Online Access: | Connect to this object online. |
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| Summary: | Deregulation of redox homeostasis is often associated with an accelerated aging process. Ribose-5-phosphate isomerase A (RPIA) mediates redox homeostasis in the pentose phosphate pathway (PPP). Our previous study demonstrated that <i>Rpi</i> knockdown boosts the healthspan in <i>Drosophila</i>. However, whether the knockdown of <i>rpia-1</i>, the <i>Rpi</i> ortholog in <i>Caenorhabditis elegans</i>, can improve the healthspan in <i>C. elegans</i> remains unknown. Here, we report that spatially and temporally limited knockdown of <i>rpia-1</i> prolongs lifespan and improves the healthspan in <i>C. elegans</i>, reflecting the evolutionarily conserved phenotypes observed in <i>Drosophila</i>. Ubiquitous and pan-neuronal knockdown of <i>rpia-1</i> both enhance tolerance to oxidative stress, reduce polyglutamine aggregation, and improve the deteriorated body bending rate caused by polyglutamine aggregation. Additionally, <i>rpia-1</i> knockdown temporally in the post-developmental stage and spatially in the neuron display enhanced lifespan. Specifically, <i>rpia-1</i> knockdown in glutamatergic or cholinergic neurons is sufficient to increase lifespan. Importantly, the lifespan extension by <i>rpia-1</i> knockdown requires the activation of autophagy and AMPK pathways and reduced TOR signaling. Moreover, the RNA-seq data support our experimental findings and reveal potential novel downstream targets. Together, our data disclose the specific spatial and temporal conditions and the molecular mechanisms for <i>rpia-1</i> knockdown-mediated longevity in <i>C. elegans</i>. These findings may help the understanding and improvement of longevity in humans. |
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| Item Description: | 10.3390/antiox12010124 2076-3921 |