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Antioxidants reveal an inverted U-shaped dose-response relationship between reactive oxygen species levels and the rate of aging in Caenorhabditis elegans.

ABSTRACT: Reactive oxygen species (ROS) are potentially toxic, but they are also signaling molecules that modulate aging. Recent observations that ROS can promote longevity have to be reconciled with the numerous claims about the benefits of antioxidants on lifespan. Here, three antioxidants [N-acetylcysteine (NAC), vitamin C, and resveratrol (RSV)] were tested on Caenorhabditis elegans mutants that alter drug uptake, mitochondrial function, and ROS metabolism. We observed that like pro-oxidants, antioxidants can both lengthen and shorten lifespan, dependent on concentration, genotypes, and conditions. The effects of antioxidants thus reveal an inverted U-shaped dose-response relationship between ROS levels and lifespan. In addition, we observed that RSV can act additively to both NAC and paraquat, to dramatically increase lifespan. This suggests that the effect of compounds that modulate ROS levels can be additive when their loci of action or mechanisms of action are sufficiently distinct.

SUBMITTER: Desjardins D

PROVIDER: S-EPMC5242296 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Antioxidants reveal an inverted U-shaped dose-response relationship between reactive oxygen species levels and the rate of aging in Caenorhabditis elegans.

Desjardins David D Cacho-Valadez Briseida B Liu Ju-Ling JL Wang Ying Y Yee Callista C Bernard Kristine K Khaki Arman A Breton Lionel L Hekimi Siegfried S

Aging cell 20160928 1

Reactive oxygen species (ROS) are potentially toxic, but they are also signaling molecules that modulate aging. Recent observations that ROS can promote longevity have to be reconciled with the numerous claims about the benefits of antioxidants on lifespan. Here, three antioxidants [N-acetylcysteine (NAC), vitamin C, and resveratrol (RSV)] were tested on Caenorhabditis elegans mutants that alter drug uptake, mitochondrial function, and ROS metabolism. We observed that like pro-oxidants, antioxid ...[more]

PMID: 27683245

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Project description:Monitoring dynamic changes in oxygen consumption rates (OCR) of a living organism in real time provide an indirect method of monitoring changes in mitochondrial function during development, aging, or malfunctioning processes. In this study, we developed a microfluidic device integrated with an optical detection system to measure the OCR of a single developing Caenorhabditis elegans (C. elegans) from postembryonic development to aging stages in real time via phase-based phosphorescence lifetime measurement. The device consists of two components: an acrylic microwell deposited with an oxygen-sensitive luminescent layer for oxygen (O₂) measurement and a microfluidic module with a pneumatically driven acrylic lid to controllably seal the microwell. We successfully measured the basal respiration (basal OCR, in pmol O₂/min/worm) of a single C. elegans inside a microwell from the stages of postembryonic development (larval stages) through adulthood to aged adult. Sequentially adding metabolic inhibitors to block bioenergetic pathways allowed us to measure the metabolic profiles of a single C. elegans at key growth and aging stages, determining the following fundamental parameters: basal OCR, adenosine triphosphate (ATP)-linked OCR, maximal OCR, reserve respiratory capacity, OCR due to proton leak, and non-mitochondrial OCR. The bioenergetic health index (BHI) was calculated from these fundamental parameters to assess the bioenergetic health of a single developing C. elegans from the postembryonic development to aging stages. The changes in BHI are correlated to C. elegans development stage, with the highest BHI = 27.5 for 4-day-old adults, which possess well-developed bioenergetic functionality. Our proposed platform demonstrates for the first time the feasibility of assessing the BHI of a single C. elegans from postembryonic development to aging stages inside a microfluidic device and provides the potential for a wide variety of biomedical applications that relate mitochondrial malfunction and diseases.

Dataset Information

Antioxidants reveal an inverted U-shaped dose-response relationship between reactive oxygen species levels and the rate of aging in Caenorhabditis elegans.

Publications

Antioxidants reveal an inverted U-shaped dose-response relationship between reactive oxygen species levels and the rate of aging in Caenorhabditis elegans.

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