Reduced neuronal expression of ribose-5-phosphate isomerase enhances tolerance to oxidative stress, extends lifespan, and attenuates polyglutamine toxicity in Drosophila

Ching Tzu Wang; Yi Chun Chen; Yi Yun Wang; Ming Hao Huang; Tzu Li Yen; Hsun Li; Cyong Jhih Liang; Tzu Kang Sang; Shih Ci Ciou; Chiou Hwa Yuh; Chao Yung Wang; Theodore J. Brummel; Horng Dar Wang

doi:10.1111/j.1474-9726.2011.00762.x

Reduced neuronal expression of ribose-5-phosphate isomerase enhances tolerance to oxidative stress, extends lifespan, and attenuates polyglutamine toxicity in Drosophila

Ching Tzu Wang, Yi Chun Chen, Yi Yun Wang, Ming Hao Huang, Tzu Li Yen, Hsun Li, Cyong Jhih Liang, Tzu Kang Sang, Shih Ci Ciou, Chiou Hwa Yuh, Chao Yung Wang, Theodore J. Brummel, Horng Dar Wang^*

^*Corresponding author for this work

School of Medicine

Research output: Contribution to journal › Journal Article › peer-review

28 Scopus citations

Abstract

Aging and age-related diseases can be viewed as the result of the lifelong accumulation of stress insults. The identification of mutant strains and genes that are responsive to stress and can alter longevity profiles provides new therapeutic targets for age-related diseases. Here we reported that a Drosophila strain with reduced expression of ribose-5-phosphate isomerase (rpi), EP2456, exhibits increased resistance to oxidative stress and enhanced lifespan. In addition, the strain also displays higher levels of NADPH. The knockdown of rpi in neurons by double-stranded RNA interference recapitulated the lifespan extension and oxidative stress resistance in Drosophila. This manipulation was also found to ameliorate the effects of genetic manipulations aimed at creating a model for studying Huntington's disease by overexpression of polyglutamine in the eye, suggesting that modulating rpi levels could serve as a treatment for normal aging as well as for polyglutamine neurotoxicity.

Original language	English
Pages (from-to)	93-103
Number of pages	11
Journal	Aging Cell
Volume	11
Issue number	1
DOIs	https://doi.org/10.1111/j.1474-9726.2011.00762.x
State	Published - 02 2012

Keywords

Drosophila
Longevity
Neuron
Oxidative stress
Pentose phosphate pathway
Polyglutamine toxicity
ribose-5-phosphate isomerase

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10.1111/j.1474-9726.2011.00762.x

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Wang, C. T., Chen, Y. C., Wang, Y. Y., Huang, M. H., Yen, T. L., Li, H., Liang, C. J., Sang, T. K., Ciou, S. C., Yuh, C. H., Wang, C. Y., Brummel, T. J., & Wang, H. D. (2012). Reduced neuronal expression of ribose-5-phosphate isomerase enhances tolerance to oxidative stress, extends lifespan, and attenuates polyglutamine toxicity in Drosophila. Aging Cell, 11(1), 93-103. https://doi.org/10.1111/j.1474-9726.2011.00762.x

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abstract = "Aging and age-related diseases can be viewed as the result of the lifelong accumulation of stress insults. The identification of mutant strains and genes that are responsive to stress and can alter longevity profiles provides new therapeutic targets for age-related diseases. Here we reported that a Drosophila strain with reduced expression of ribose-5-phosphate isomerase (rpi), EP2456, exhibits increased resistance to oxidative stress and enhanced lifespan. In addition, the strain also displays higher levels of NADPH. The knockdown of rpi in neurons by double-stranded RNA interference recapitulated the lifespan extension and oxidative stress resistance in Drosophila. This manipulation was also found to ameliorate the effects of genetic manipulations aimed at creating a model for studying Huntington's disease by overexpression of polyglutamine in the eye, suggesting that modulating rpi levels could serve as a treatment for normal aging as well as for polyglutamine neurotoxicity.",

keywords = "Drosophila, Longevity, Neuron, Oxidative stress, Pentose phosphate pathway, Polyglutamine toxicity, ribose-5-phosphate isomerase",

author = "Wang, {Ching Tzu} and Chen, {Yi Chun} and Wang, {Yi Yun} and Huang, {Ming Hao} and Yen, {Tzu Li} and Hsun Li and Liang, {Cyong Jhih} and Sang, {Tzu Kang} and Ciou, {Shih Ci} and Yuh, {Chiou Hwa} and Wang, {Chao Yung} and Brummel, {Theodore J.} and Wang, {Horng Dar}",

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doi = "10.1111/j.1474-9726.2011.00762.x",

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Wang, CT, Chen, YC, Wang, YY, Huang, MH, Yen, TL, Li, H, Liang, CJ, Sang, TK, Ciou, SC, Yuh, CH, Wang, CY, Brummel, TJ & Wang, HD 2012, 'Reduced neuronal expression of ribose-5-phosphate isomerase enhances tolerance to oxidative stress, extends lifespan, and attenuates polyglutamine toxicity in Drosophila', Aging Cell, vol. 11, no. 1, pp. 93-103. https://doi.org/10.1111/j.1474-9726.2011.00762.x

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AU - Wang, Ching Tzu

AU - Chen, Yi Chun

AU - Wang, Yi Yun

AU - Huang, Ming Hao

AU - Yen, Tzu Li

AU - Li, Hsun

AU - Liang, Cyong Jhih

AU - Sang, Tzu Kang

AU - Ciou, Shih Ci

AU - Yuh, Chiou Hwa

AU - Wang, Chao Yung

AU - Brummel, Theodore J.

AU - Wang, Horng Dar

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AB - Aging and age-related diseases can be viewed as the result of the lifelong accumulation of stress insults. The identification of mutant strains and genes that are responsive to stress and can alter longevity profiles provides new therapeutic targets for age-related diseases. Here we reported that a Drosophila strain with reduced expression of ribose-5-phosphate isomerase (rpi), EP2456, exhibits increased resistance to oxidative stress and enhanced lifespan. In addition, the strain also displays higher levels of NADPH. The knockdown of rpi in neurons by double-stranded RNA interference recapitulated the lifespan extension and oxidative stress resistance in Drosophila. This manipulation was also found to ameliorate the effects of genetic manipulations aimed at creating a model for studying Huntington's disease by overexpression of polyglutamine in the eye, suggesting that modulating rpi levels could serve as a treatment for normal aging as well as for polyglutamine neurotoxicity.

KW - Drosophila

KW - Longevity

KW - Neuron

KW - Oxidative stress

KW - Pentose phosphate pathway

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Reduced neuronal expression of ribose-5-phosphate isomerase enhances tolerance to oxidative stress, extends lifespan, and attenuates polyglutamine toxicity in Drosophila

Abstract

Keywords

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