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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302
THE GENETICS OF CAENORHABDITIS ELEGANS
Brenner, S. (1974) · Genetics · doi:10.1093/genetics/77.1.71 · Cited by 15,220
Free Radicals in the Physiological Control of Cell Function
Dröge, W. (2002) · Physiological Reviews · doi:10.1152/physrev.00018.2001 · Cited by 9,855
Aging: a theory based on free radical and radiation chemistry
Harman, D. (1956) · Journal of Gerontology · doi:10.1093/geronj/11.3.298 · Cited by 8,567
Systematic functional analysis of the Caenorhabditis elegans genome using RNAi
Kamath, R. S., Fraser, A. G., Yan, D., Poulin, G. B., Durbin, R. M., Gotta, M., Kanapin, A. A., Bot, N. L., Moreno, S., Sohrmann, M., et al. (2003) · Nature · doi:10.1038/nature01278 · Cited by 3,629
A C. elegans mutant that lives twice as long as wild type
Kenyon, C., Chang, J., Gensch, E., Rudner, A., & Tabtiang, R. (1993) · Nature · doi:10.1038/366461a0 · Cited by 3,387
Kahn, B. B., Alquier, T., Carling, D., & Hardie, D. G. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2004.12.003 · Cited by 2,799
Bjelakovic, G., Nikolova, D., Gluud, L. L., Simonetti, R. G., & Gluud, C. (2007) · JAMA · doi:10.1001/jama.297.8.842 · Cited by 2,275
Intake of sugar-sweetened beverages and weight gain: a systematic review
Malik, V. S., Schulze, M. B., & Hu, F. B. (2006) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/84.2.274 · Cited by 2,100
Lin, S.-J., Defossez, P.-A., & Guarente, L. (2000) · Science · doi:10.1126/science.289.5487.2126 · Cited by 1,775
Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans
Tissenbaum, H. A., & Guarente, L. (2001) · Nature · doi:10.1038/35065638 · Cited by 1,603
Genome-wide RNAi screening in Caenorhabditis elegans
Kamath, R. S. (2003) · Methods · doi:10.1016/s1046-2023(03)00050-1 · Cited by 1,547
The retardation of aging and disease by dietary restriction
(1989) · Choice Reviews Online · doi:10.5860/choice.26-5101 · Cited by 1,477
Extended Longevity in Mice Lacking the Insulin Receptor in Adipose Tissue
Blüher, M., Kahn, B. B., & Kahn, C. R. (2003) · Science · doi:10.1126/science.1078223 · Cited by 1,155
Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration
Lin, S.-J., Kaeberlein, M., Andalis, A. A., Sturtz, L. A., Defossez, P.-A., Culotta, V. C., Fink, G. R., & Guarente, L. (2002) · Nature · doi:10.1038/nature00829 · Cited by 1,057
The genetics of caloric restriction in Caenorhabditis elegans
Lakowski, B., & Hekimi, S. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.22.13091 · Cited by 971
Heilbronn, L. K., de Jonge, L., Frisard, M. I., DeLany, J. P., Larson-Meyer, D. E., Rood, J., Nguyen, T., Martin, C. K., Volaufova, J., Most, M. M., et al. (2006) · JAMA · doi:10.1001/jama.295.13.1539 · Cited by 969
A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity
Lee, S. S., Lee, R. Y. N., Fraser, A. G., Kamath, R. S., Ahringer, J., & Ruvkun, G. (2003) · Nature Genetics · doi:10.1038/ng1056 · Cited by 969
Body size, energy metabolism and lifespan
Speakman, J. R. (2005) · Journal of Experimental Biology · doi:10.1242/jeb.01556 · Cited by 914
Adiposity as Compared with Physical Activity in Predicting Mortality among Women
Hu, F. B., Willett, W. C., Li, T., Stampfer, M. J., Colditz, G. A., & Manson, J. E. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa042135 · Cited by 820
Klass, M. R. (1977) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(77)90043-4 · Cited by 806
Garigan, D., Hsu, A.-L., Fraser, A. G., Kamath, R. S., Ahringer, J., & Kenyon, C. (2002) · Genetics · doi:10.1093/genetics/161.3.1101 · Cited by 803
Speakman, J. R., Talbot, D. A., Selman, C., Snart, S., McLaren, J. S., Redman, P., Krol, E., Jackson, D. M., Johnson, M. S., & Brand, M. D. (2004) · Aging Cell · doi:10.1111/j.1474-9728.2004.00097.x · Cited by 761
DAF-16 Target Genes That Control C. elegans Life-Span and Metabolism
Lee, S. S., Kennedy, S., Tolonen, A. C., & Ruvkun, G. (2003) · Science · doi:10.1126/science.1083614 · Cited by 669
Two neurons mediate diet-restriction-induced longevity in C. elegans
Bishop, N. A., & Guarente, L. (2007) · Nature · doi:10.1038/nature05904 · Cited by 643
Apfeld, J., O'Connor, G., McDonagh, T., DiStefano, P. S., & Curtis, R. (2004) · Genes & Development · doi:10.1101/gad.1255404 · Cited by 643
Active sugar transport in health and disease
Wright, E. M., Hirayama, B. A., & Loo, D. F. (2007) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2006.01746.x · Cited by 627
SUBSTRATE SPECIFICITY OF BRAIN HEXOKINASE
Sols, A., & Crane, R. K. (1954) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)65384-0 · Cited by 599
Daily activity energy expenditure and mortality among older adults
Manini, T. M., Everhart, J. E., Patel, K. V., Schoeller, D. A., Colbert, L. H., Visser, M., Tylavsky, F., Bauer, D. C., Goodpaster, B. H., & Harris, T. B. (2006) · JAMA · doi:10.1001/jama.296.2.171 · Cited by 598
Toward a unified theory of caloric restriction and longevity regulation
Sinclair, D. A. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2005.03.019 · Cited by 568
Hansen, M., Hsu, A., Dillin, A. G., & Kenyon, C. J. (2005) · PLoS Genetics · doi:10.1371/journal.pgen.0010017 · Cited by 543
PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegans
Panowski, S. H., Wolff, S., Aguilaniu, H., Durieux, J., & Dillin, A. G. (2007) · Nature · doi:10.1038/nature05837 · Cited by 538
Brain IRS2 Signaling Coordinates Life Span and Nutrient Homeostasis
Taguchi, A., Wartschow, L. M., & White, M. F. (2007) · Science · doi:10.1126/science.1142179 · Cited by 523
A systematic RNAi screen for longevity genes in C. elegansPreprint
Hamilton, B., Dong, Y., Shindo, M., Liu, W., Odell, I., Ruvkun, G., & Lee, S. S. (2005) · Genes & Development · doi:10.1101/gad.1308205 · Cited by 513
The Sweetening of the World's Diet
Popkin, B. M., & Nielsen, S. J. (2003) · Obesity Research · doi:10.1038/oby.2003.179 · Cited by 466
Calorie restriction mimetics: an emerging research field
Ingram, D. K., Zhu, M., Mamczarz, J., Zou, S., Lane, M. A., Roth, G. S., & de Cabo, R. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00202.x · Cited by 424
Oxidative stress and ageing in Caenorhabditis elegans
Vanfleteren, J. R. (1993) · Biochemical Journal · doi:10.1042/bj2920605 · Cited by 383
Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis elegans
Wilson, M. A., Shukitt‐Hale, B., Kalt, W., Ingram, D. K., Joseph, J. A., & Wolkow, C. A. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00192.x · Cited by 380
Oh, S. W., Mukhopadhyay, A., Dixit, B. L., Raha, T., Green, M. R., & Tissenbaum, H. A. (2005) · Nature Genetics · doi:10.1038/ng1723 · Cited by 374
Effects of extract of western red-cedar heartwood on certain wood-decaying fungi in culture
Southam, C. M., & Ehrlich, J. (1943) · Phytopathology · Cited by 367
Lifespan extension in Caenorhabditis elegans by complete removal of food
Kaeberlein, T. L., Smith, E. D., Tsuchiya, M., Welton, K. L., Thomas, J. H., Fields, S., Kennedy, B. K., & Kaeberlein, M. R. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00238.x · Cited by 350
Multiple Stressors in Caenorhabditis elegans Induce Stress Hormesis and Extended Longevity
Cypser, J. R., & Johnson, T. E. (2002) · The Journals of Gerontology Series A · doi:10.1093/gerona/57.3.b109 · Cited by 336
Plasma antioxidant status and cell injury after severe physical exercise
Chevion, S., Moran, D. S., Heled, Y., Shani, Y., Regev, G. J., Abbou, B., Berenshtein, E., Stadtman, E. R., & Epstein, Y. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0831097100 · Cited by 282
Genome-Wide Prediction of C. elegans Genetic Interactions
Zhong, W., & Sternberg, P. W. (2006) · Science · doi:10.1126/science.1123287 · Cited by 270
Houthoofd, K. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(03)00161-x · Cited by 245
Frataxin activates mitochondrial energy conversion and oxidative phosphorylation
Ristow, M., Pfister, M. F., Yee, A. J., Schubert, M., Michael, L., Zhang, C., Ueki, K., Michael, M. D., Lowell, B. B., & Kahn, C. R. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.220403797 · Cited by 221
Self-citationCurtis, R., O'Connor, G., & DiStefano, P. S. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00205.x · Cited by 220
Houthoofd, K., Braeckman, B. P., Lenaerts, I., Brys, K., Vreese, A. D., Eygen, S. V., & Vanfleteren, J. R. (2002) · Experimental Gerontology · doi:10.1016/s0531-5565(02)00173-0 · Cited by 211
Induction of Oxidative Metabolism by Mitochondrial Frataxin Inhibits Cancer Growth
Schulz, T. J., Thierbach, R., Voigt, A., Drewes, G., Mietzner, B., Steinberg, P., Pfeiffer, A. F. H., & Ristow, M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m511064200 · Cited by 198
Self-citationIncreased Life Span due to Calorie Restriction in Respiratory-Deficient Yeast
Kaeberlein, M. R., Hu, D., Kerr, E. O., Tsuchiya, M., Westman, E. A., Dang, N., Fields, S., & Kennedy, B. K. (2005) · PLoS Genetics · doi:10.1371/journal.pgen.0010069 · Cited by 193
Kampkötter, A., Nkwonkam, C. G., Zurawski, R. F., Timpel, C., Chovolou, Y., Wätjen, W., & Kahl, R. (2007) · Archives of Toxicology · doi:10.1007/s00204-007-0215-4 · Cited by 190
Johnson, T. E., Henderson, S. T., Murakami, S., de Castro, E., de Castro, S. H., Cypser, J. R., Rikke, B. A., Tedesco, P., & Link, C. D. (2002) · Journal of Inherited Metabolic Disease · doi:10.1023/a:1015677828407 · Cited by 174
Self-report of physical activity and patterns of mortality in seventh-day adventist men
Lindsted, K. D., Tonstad, S., & Kuzma, J. W. (1991) · Journal of Clinical Epidemiology · doi:10.1016/0895-4356(91)90074-j · Cited by 156
The rate of living : being an account of some experimental studies on the biology of life duration
Pearl, R. (1928) · A.A. Knopf eBooks · Cited by 131
No reduction of metabolic rate in food restricted Caenorhabditis elegans
Houthoofd, K., Braeckman, B. P., Lenaerts, I., Brys, K., Vreese, A. D., Eygen, S. V., & Vanfleteren, J. R. (2002) · Experimental Gerontology · doi:10.1016/s0531-5565(02)00172-9 · Cited by 129
Thierbach, R., Schulz, T. J., Isken, F., Voigt, A., Mietzner, B., Drewes, G., von Kleist-Retzow, J.-C., Wiesner, R. J., Magnuson, M. A., Puccio, H., et al. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi410 · Cited by 127
Self-citationBrys, K., Vanfleteren, J. R., & Braeckman, B. P. (2007) · Experimental Gerontology · doi:10.1016/j.exger.2007.02.004 · Cited by 112
A Metabolic Model for Life Span Determination in Caenorhabditis elegans
Rea, S. L., & Johnson, T. E. (2003) · Developmental Cell · doi:10.1016/s1534-5807(03)00242-9 · Cited by 111
Sodium-glucose cotransporter inhibitors for diabetes.
Isaji, M. (2007) · PubMed · Cited by 86
Dietary restriction-induced life extension: a broadly based biological phenomenon
Masoro, E. J. (2006) · Biogerontology · doi:10.1007/s10522-006-9015-0 · Cited by 85
Applying hormesis in aging research and therapy
Rattan, S. (2001) · Human & Experimental Toxicology · doi:10.1191/096032701701548034 · Cited by 84
Zarse, K., Schulz, T. J., Birringer, M., & Ristow, M. (2007) · The FASEB Journal · doi:10.1096/fj.06-6994com · Cited by 58
Self-citationMrg19 depletion increases S. cerevisiae lifespan by augmenting ROS defence
Kharade, S. V., Mittal, N., Das, S. P., Sinha, P., & Roy, N. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.11.017 · Cited by 40
Sinclair, D. A., Lin, S.-J., & Guarente, L. (2006) · Science · doi:10.1126/science.312.5771.195d · Cited by 36
Cited by
Sorted by citations
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
Finkel, T. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201102095 · Cited by 2,322
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
