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

David Desjardins,Lionel Breton,Arman Khaki,Kristine Bernard,Ying Wang,Ju‐Ling Liu,Callista Yee,Siegfried Hekimi,Briseida Cacho‐Valadez

doi:10.1111/acel.12528

David Desjardins, Lionel Breton + Show 7 more

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https://doi.org/10.1111/acel.12528

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Journal: Aging Cell	Publication Date: Sep 28, 2016
Citations: 68	License type: CC BY 4.0

Affiliation: McGill University, L'Oréal (France)

Abstract

SummaryReactive 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.

Highlights

Reactive oxygen species (ROS), such as superoxide and peroxide, are potentially toxic by-products of energy metabolism as well as signaling molecules (Holmstrom & Finkel, 2014)
Resveratrol is relatively insoluble in aqueous media and needs to be dissolved in DMSO for addition to standard nematode growth medium (NGM) plates
To allow for appropriate comparisons, we tested all three antioxidants (RSV, NAC, and Vitamin C (VitC)) at the same concentration of DMSO, NAC and VitC are readily soluble in NGM without DMSO

Summary

Introduction

Reactive oxygen species (ROS), such as superoxide and peroxide, are potentially toxic by-products of energy metabolism as well as signaling molecules (Holmstrom & Finkel, 2014). Both types of properties have been firmly implicated in the aging process, in particular in the nematode Caenorhabditis elegans (Van Raamsdonk & Hekimi, 2010; Yang & Hekimi, 2010a). An indirect method to overcome this difficulty is to measure ROS damage to macromolecules. Measuring ROS damage cannot reveal any causal role ROS might play in the aging process. Many studies have relied on studying the effects of exogenous compounds that increase the Accepted for publication 16 August 2016 generation of ROS (pro-oxidants) or compounds that help to neutralize ROS (antioxidants)

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