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Antioxidants
Volume 12
Issue 1
10.3390/antiox12010124
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Article

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

by
Wen-Chi Shen
1,
Chiou-Hwa Yuh
2,
Yu-Ting Lu
1,
Yen-Hung Lin
1,
Tsui-Ting Ching
3,
Chao-Yung Wang
4 and
Horng-Dar Wang
1,5,*
1
Institute of Biotechnology, National Tsing Hua University, HsinChu 300044, Taiwan
2
Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Mioali Country 35053, Taiwan
3
Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
4
Department of Cardiology, Chang Gung Memory Hospital, Linkou Main Branch, Chang Gung University, Taoyuan 33305, Taiwan
5
Department of Life Science, National Tsing Hua University, HsinChu 300044, Taiwan
*
Author to whom correspondence should be addressed.
Antioxidants 2023, 12(1), 124; https://doi.org/10.3390/antiox12010124
Submission received: 14 November 2022 / Revised: 30 December 2022 / Accepted: 31 December 2022 / Published: 4 January 2023
(This article belongs to the Special Issue Something is Rotten in the State of Redox)
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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.
Keywords: ribose-5-phosphate isomerase A (RPIA); pentose phosphate pathway (PPP); autophagy; AMP activated protein kinase (AMPK); target of rapamycin (TOR); lifespan; C. elegans ribose-5-phosphate isomerase A (RPIA); pentose phosphate pathway (PPP); autophagy; AMP activated protein kinase (AMPK); target of rapamycin (TOR); lifespan; C. elegans
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MDPI and ACS Style

Shen, W.-C.; Yuh, C.-H.; Lu, Y.-T.; Lin, Y.-H.; Ching, T.-T.; Wang, C.-Y.; Wang, H.-D. Reduced Ribose-5-Phosphate Isomerase A-1 Expression in Specific Neurons and Time Points Promotes Longevity in Caenorhabditis elegans. Antioxidants 2023, 12, 124. https://doi.org/10.3390/antiox12010124

AMA Style

Shen W-C, Yuh C-H, Lu Y-T, Lin Y-H, Ching T-T, Wang C-Y, Wang H-D. Reduced Ribose-5-Phosphate Isomerase A-1 Expression in Specific Neurons and Time Points Promotes Longevity in Caenorhabditis elegans. Antioxidants. 2023; 12(1):124. https://doi.org/10.3390/antiox12010124

Chicago/Turabian Style

Shen, Wen-Chi, Chiou-Hwa Yuh, Yu-Ting Lu, Yen-Hung Lin, Tsui-Ting Ching, Chao-Yung Wang, and Horng-Dar Wang. 2023. "Reduced Ribose-5-Phosphate Isomerase A-1 Expression in Specific Neurons and Time Points Promotes Longevity in Caenorhabditis elegans" Antioxidants 12, no. 1: 124. https://doi.org/10.3390/antiox12010124

APA Style

Shen, W.-C., Yuh, C.-H., Lu, Y.-T., Lin, Y.-H., Ching, T.-T., Wang, C.-Y., & Wang, H.-D. (2023). Reduced Ribose-5-Phosphate Isomerase A-1 Expression in Specific Neurons and Time Points Promotes Longevity in Caenorhabditis elegans. Antioxidants, 12(1), 124. https://doi.org/10.3390/antiox12010124

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