Antioxidants reveal an inverted U-shaped dose-response relationship between reactive oxygen species levels and the rate of aging in Caenorhabditis elegans.
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.
Department of Biology, McGill University, Montreal, QC, Canada, H3A 1B1.
David
D
Desjardins
Department of Biology, McGill University, Montreal, QC, Canada, H3A 1B1.
Briseida
B
Cacho-Valadez
Department of Biology, McGill University, Montreal, QC, Canada, H3A 1B1.
Ju-Ling
JL
Liu
Department of Biology, McGill University, Montreal, QC, Canada, H3A 1B1.
Ying
Y
Wang
Department of Biology, McGill University, Montreal, QC, Canada, H3A 1B1.
Callista
C
Yee
Department of Biology, McGill University, Montreal, QC, Canada, H3A 1B1.
Kristine
K
Bernard
Department of Biology, McGill University, Montreal, QC, Canada, H3A 1B1.
Arman
A
Khaki
L'Oréal Research and Innovation, Aulnay sous bois, 93600, France.
Lionel
L
Breton
Department of Biology, McGill University, Montreal, QC, Canada, H3A 1B1.
Siegfried
S
Hekimi
D000111:Acetylcysteine / Q000494:pharmacology; D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000502:physiology*; D008136:Longevity / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D010269:Paraquat / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D017382:Reactive Oxygen Species; D013267:Stilbenes; D013482:Superoxide Dismutase; D010269:Paraquat; D001205:Ascorbic Acid; D000077185:Resveratrol; D000111:Acetylcysteine

C. elegans
; aging; antioxidants; prooxidants; reactive oxygen species
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