Reduced Ribose-5-Phosphate Isomerase A-1 Expression in Specific Neurons and Time Points Promotes Longevity in Caenorhabditis elegans

Wen Chi Shen, Chiou Hwa Yuh, Yu Ting Lu, Yen Hung Lin, Tsui Ting Ching, Chao Yung Wang, Horng Dar Wang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

2 Scopus citations


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 Rpi knockdown boosts the healthspan in Drosophila. However, whether the knockdown of rpia-1, the Rpi ortholog in Caenorhabditis elegans, can improve the healthspan in C. elegans remains unknown. Here, we report that spatially and temporally limited knockdown of rpia-1 prolongs lifespan and improves the healthspan in C. elegans, reflecting the evolutionarily conserved phenotypes observed in Drosophila. Ubiquitous and pan-neuronal knockdown of rpia-1 both enhance tolerance to oxidative stress, reduce polyglutamine aggregation, and improve the deteriorated body bending rate caused by polyglutamine aggregation. Additionally, rpia-1 knockdown temporally in the post-developmental stage and spatially in the neuron display enhanced lifespan. Specifically, rpia-1 knockdown in glutamatergic or cholinergic neurons is sufficient to increase lifespan. Importantly, the lifespan extension by rpia-1 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 rpia-1 knockdown-mediated longevity in C. elegans. These findings may help the understanding and improvement of longevity in humans.

Original languageEnglish
Article number124
Issue number1
StatePublished - 04 01 2023

Bibliographical note

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  • AMP activated protein kinase (AMPK)
  • C. elegans
  • autophagy
  • lifespan
  • pentose phosphate pathway (PPP)
  • ribose-5-phosphate isomerase A (RPIA)
  • target of rapamycin (TOR)


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