The DOI matches its Crossref record; 64 of the 65 references it cites were found in a registry or an index.
Glucose Restriction Extends Caenorhabditis elegans Life Span by Inducing Mitochondrial Respiration and Increasing Oxidative Stress
Open accessAbstract
Increasing cellular glucose uptake is a fundamental concept in treatment of type 2 diabetes, whereas nutritive calorie restriction increases life expectancy. We show here that increased glucose availability decreases Caenorhabditis elegans life span, while impaired glucose metabolism extends life expectancy by inducing mitochondrial respiration. The histone deacetylase Sir2.1 is found here to be dispensable for this phenotype, whereas disruption of aak-2, a homolog of AMP-dependent kinase (AMPK), abolishes extension of life span due to impaired glycolysis. Reduced glucose availability promotes formation of reactive oxygen species (ROS), induces catalase activity, and increases oxidative stress resistance and survival rates, altogether providing direct evidence for a hitherto hypothetical concept named mitochondrial hormesis or "mitohormesis." Accordingly, treatment of nematodes with different antioxidants and vitamins prevents extension of life span. In summary, these data indicate that glucose restriction promotes mitochondrial metabolism, causing increased ROS formation and cumulating in hormetic extension of life span, questioning current treatments of type 2 diabetes as well as the widespread use of antioxidant supplements.
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In the citing paper
“Although the mechanisms behind calorie restriction-driven longevity extension are still poorly understood, mitochondrial physiology is involved in the beneficial effects of calorie restriction in budding yeast11 and Caenorhabditis elegans12, as well as in mammals13.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [12]
In the citing paper
“Treatment of worms with antioxidants abolished this life extension 97.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [97]
In the citing paper
“Furthermore, in C. elegans, lifespan extension mediated by glucose restriction is associated with increased mitochondrial metabolism and ROS production.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [97]
In the citing paper
“This theory can be applied to mitochondrial ROS 97”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [97]
Citations
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Cited by
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ROS function in redox signaling and oxidative stress
Schieber, M., & Chandel, N. S. (2014) · Current Biology · doi:10.1016/j.cub.2014.03.034 · Cited by 6,931
AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint
Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.003 · Cited by 3,849
Kenyon, C. J. (2010) · Nature · doi:10.1038/nature08980 · Cited by 2,739
Physiological Roles of Mitochondrial Reactive Oxygen Species
Sena, L. A., & Chandel, N. S. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.09.025 · Cited by 2,632
Signal transduction by reactive oxygen species
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Metadata
- Authors
- Schulz, T. J., Zarse, K., Voigt, A., Urban, N., Birringer, M., & Ristow, M.
- Affiliations
- German Institute of Human Nutrition (DE)
- Friedrich Schiller University Jena (DE)
- Corresponding author
- Ristow, Michael
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 6
- Issue
- 4
- Pages
- 280-293
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2056673369
- Cited by
- 1,209
- References
- 65
- Citations by year
- 2026: 21 · 2025: 43 · 2024: 44 · 2023: 63 · 2022: 61 · 2021: 66 · 2020: 68 · 2019: 67 · 2018: 75 · 2017: 68 · 2016: 90 · 2015: 82 · 2014: 92 · 2013: 77 · 2012: 70
- FWCI
- 14.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- glucose restriction, lifespan extension, Caenorhabditis elegans, mitochondrial respiration, oxidative stress, reactive oxygen species, aak-2, AMPK, glycolysis, catalase, antioxidants, type 2 diabetes, caloric restriction
- MeSH terms
- Animals, Glucose, Glycolysis, Longevity, Mitochondria, Multienzyme Complexes, Caenorhabditis elegans, Protein Serine-Threonine Kinases, Reactive Oxygen Species, Oxidative Stress, Cell Respiration, Caenorhabditis elegans Proteins, Sirtuins, AMP-Activated Protein Kinases
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