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© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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.

Details

Title
Reduced Ribose-5-Phosphate Isomerase A-1 Expression in Specific Neurons and Time Points Promotes Longevity in Caenorhabditis elegans
Author
Wen-Chi, Shen 1 ; Chiou-Hwa Yuh 2   VIAFID ORCID Logo  ; Yu-Ting, Lu 1 ; Yen-Hung, Lin 1 ; Tsui-Ting, Ching 3   VIAFID ORCID Logo  ; Chao-Yung, Wang 4 ; Wang, Horng-Dar 5   VIAFID ORCID Logo 

 Institute of Biotechnology, National Tsing Hua University, HsinChu 300044, Taiwan 
 Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Mioali Country 35053, Taiwan 
 Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan 
 Department of Cardiology, Chang Gung Memory Hospital, Linkou Main Branch, Chang Gung University, Taoyuan 33305, Taiwan 
 Institute of Biotechnology, National Tsing Hua University, HsinChu 300044, Taiwan; Department of Life Science, National Tsing Hua University, HsinChu 300044, Taiwan 
First page
124
Publication year
2023
Publication date
2023
Publisher
MDPI AG
e-ISSN
20763921
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2767126050
Copyright
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.