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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Mitochondrial physiology is involved in the beneficial effects of calorie restriction in budding yeast, C. elegans, and mammals.
“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]
Treatment of worms with antioxidants abolished the life extension mediated by glucose restriction.
“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 C. elegans, lifespan extension mediated by glucose restriction is associated with increased mitochondrial metabolism and ROS production.
“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]
The theory of hormesis can be applied to mitochondrial ROS.
“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]
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302 · see citing works
THE GENETICS OF CAENORHABDITIS ELEGANS
Brenner, S. (1974) · Genetics · doi:10.1093/genetics/77.1.71 · Cited by 14,984 · see citing works
Free Radicals in the Physiological Control of Cell Function
Dröge, W. (2002) · Physiological Reviews · doi:10.1152/physrev.00018.2001 · Cited by 9,855 · see citing works
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 · see citing works
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 3,542 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 1,918 · see citing works
Lin, S.-J., Defossez, P.-A., & Guarente, L. (2000) · Science · doi:10.1126/science.289.5487.2126 · Cited by 1,775 · see citing works
Genome-wide RNAi screening in Caenorhabditis elegans
Kamath, R. S. (2003) · Methods · doi:10.1016/s1046-2023(03)00050-1 · Cited by 1,562 · see citing works
The retardation of aging and disease by dietary restriction
(1989) · Choice Reviews Online · doi:10.5860/choice.26-5101 · Cited by 1,477 · see citing works
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 1,348 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 967 · see citing works
Body size, energy metabolism and lifespan
Speakman, J. R. (2005) · Journal of Experimental Biology · doi:10.1242/jeb.01556 · Cited by 914 · see citing works
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 · see citing works
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 798 · see citing works
Klass, M. R. (1977) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(77)90043-4 · Cited by 793 · see citing works
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 · see citing works
DAF-16 Target Genes That Control <i>C. elegans</i> Life-Span and Metabolism
Lee, S. S., Kennedy, S., Tolonen, A. C., & Ruvkun, G. (2003) · Science · doi:10.1126/science.1083614 · Cited by 669 · see citing works
Two neurons mediate diet-restriction-induced longevity in C. elegans
Bishop, N. A., & Guarente, L. (2007) · Nature · doi:10.1038/nature05904 · Cited by 643 · see citing works
Apfeld, J., O'Connor, G., McDonagh, T., DiStefano, P. S., & Curtis, R. (2004) · Genes & Development · doi:10.1101/gad.1255404 · Cited by 643 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 561 · see citing works
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 · see citing works
Hansen, M., Hsu, A., Dillin, A. G., & Kenyon, C. J. (2005) · PLoS Genetics · doi:10.1371/journal.pgen.0010017 · Cited by 533 · see citing works
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 · see citing works
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 · see citing works
The Sweetening of the World's Diet
Popkin, B. M., & Nielsen, S. J. (2003) · Obesity Research · doi:10.1038/oby.2003.179 · Cited by 453 · see citing works
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 415 · see citing works
Oxidative stress and ageing in Caenorhabditis elegans
Vanfleteren, J. R. (1993) · Biochemical Journal · doi:10.1042/bj2920605 · Cited by 383 · see citing works
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 · see citing works
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 374 · see citing works
Effects of extract of western red-cedar heartwood on certain wood-decaying fungi in culture
Southam, C. M., & Ehrlich, J. (1943) · Phytopathology · Cited by 370 · see citing works
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 · see citing works
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 336 · see citing works
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 · see citing works
Genome-Wide Prediction of C. elegans Genetic Interactions
Zhong, W., & Sternberg, P. W. (2006) · Science · doi:10.1126/science.1123287 · Cited by 270 · see citing works
Houthoofd, K. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(03)00161-x · Cited by 245 · see citing works
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 · see citing works
Self-citationCurtis, R., O'Connor, G., & DiStefano, P. S. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00205.x · Cited by 215 · see citing works
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 · see citing works
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 · see citing works
Self-citationKampkötter, 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 · see citing works
Increased 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 190 · see citing works
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 · see citing works
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 · see citing works
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 133 · see citing works
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 · see citing works
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 · see citing works
Self-citationA 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 · see citing works
Brys, K., Vanfleteren, J. R., & Braeckman, B. P. (2007) · Experimental Gerontology · doi:10.1016/j.exger.2007.02.004 · Cited by 107 · see citing works
Sodium-glucose cotransporter inhibitors for diabetes.
Isaji, M. (2007) · PubMed · Cited by 86 · see citing works
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 · see citing works
Applying hormesis in aging research and therapy
Rattan, S. (2001) · Human & Experimental Toxicology · doi:10.1191/096032701701548034 · Cited by 84 · see citing works
Zarse, K., Schulz, T. J., Birringer, M., & Ristow, M. (2007) · The FASEB Journal · doi:10.1096/fj.06-6994com · Cited by 58 · see citing works
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 · see citing works
Sinclair, D. A., Lin, S.-J., & Guarente, L. (2006) · Science · doi:10.1126/science.312.5771.195d · Cited by 36 · see citing works
Flagged first, then by citations
1 of the 65 references couldn’t be matched to a known paper.
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 · see citing works
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 · see citing works
Kenyon, C. J. (2010) · Nature · doi:10.1038/nature08980 · Cited by 2,739 · see citing works
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 · see citing works
Signal transduction by reactive oxygen species
Finkel, T. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201102095 · Cited by 2,322 · see citing works
Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling
Wang, Y., Branicky, R. S., Noë, A., & Hekimi, S. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201708007 · Cited by 2,199 · see citing works
Cellular mechanisms and physiological consequences of redox-dependent signalling
Holmström, K. M., & Finkel, T. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3801 · Cited by 2,093 · see citing works
Steinberg, G. R., & Kemp, B. E. (2009) · Physiological Reviews · doi:10.1152/physrev.00011.2008 · Cited by 1,633 · see citing works
Antioxidants prevent health-promoting effects of physical exercise in humans
Ristow, M., Zarse, K., Oberbach, A., Klöting, N., Birringer, M., Kiehntopf, M., Stumvoll, M., Kahn, C. R., & Blüher, M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903485106 · Cited by 1,582 · see citing works
Self-citationMitochondrial ROS Signaling in Organismal Homeostasis
Shadel, G. S., & Horvath, T. L. (2015) · Cell · doi:10.1016/j.cell.2015.10.001 · Cited by 1,353 · see citing works
Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation
Qiu, X., Brown, K., Hirschey, M. D., Verdin, E., & Chen, D. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.11.015 · Cited by 1,310 · see citing works
Achieving the Balance between ROS and Antioxidants: When to Use the Synthetic Antioxidants
Poljsak, B., Šuput, D., & Milisav, I. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/956792 · Cited by 1,301 · see citing works
Lubos, E., Loscalzo, J., & Handy, D. E. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2010.3586 · Cited by 1,280 · see citing works
Cellular Adaptation to Hypoxia through Hypoxia Inducible Factors and beyond
Lee, P., Chandel, N. S., & Simon, M. C. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0227-y · Cited by 1,272 · see citing works
Radical-free biology of oxidative stress
Jones, D. P. (2008) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00283.2008 · Cited by 1,213 · see citing works
Mouchiroud, L., Houtkooper, R. H., Moullan, N., Katsyuba, E., Ryu, D., Cantó, C., Mottis, A., Jo, Y.-S., Viswanathan, M., Schoonjans, K., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.016 · Cited by 1,210 · see citing works
Oxidative Stress as a Major Culprit in Kidney Disease in Diabetes
Forbes, J. M., Coughlan, M. T., & Cooper, M. E. (2008) · Diabetes · doi:10.2337/db08-0057 · Cited by 1,203 · see citing works
Spermidine in health and disease
Madeo, F., Eisenberg, T., Pietrocola, F., & Kroemer, G. (2018) · Science · doi:10.1126/science.aan2788 · Cited by 1,154 · see citing works
The role of mitochondria in aging
Bratic, A., & Larsson, N.-G. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64125 · Cited by 1,087 · see citing works
Mitonuclear protein imbalance as a conserved longevity mechanism
Houtkooper, R. H., Mouchiroud, L., Ryu, D., Moullan, N., Katsyuba, E., Knott, G., Williams, R. W., & Auwerx, J. (2013) · Nature · doi:10.1038/nature12188 · Cited by 1,035 · see citing works
Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes
Hamanaka, R. B., & Chandel, N. S. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.04.002 · Cited by 1,011 · see citing works
Mitochondrial and metabolic dysfunction in ageing and age-related diseases
Amorim, J. A., Coppotelli, G., Rolo, A. P., Palmeira, C. M., Ross, J. M., & Sinclair, D. A. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00626-7 · Cited by 990 · see citing works
Oxidation events and skin aging
Kammeyer, A., & Luiten, R. M. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.01.001 · Cited by 980 · see citing works
Bjelakovic, G., Nikolova, D., Gluud, L. L., Simonetti, R. G., & Gluud, C. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007176.pub2 · Cited by 924 · see citing works
Cantó, C., Jiang, L. Q., Deshmukh, A. S., Mataki, C., Coste, A., Lagouge, M., Zierath, J. R., & Auwerx, J. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.02.006 · Cited by 921 · see citing works
Animal models of obesity and diabetes mellitus
Kleinert, M., Clemmensen, C., Hofmann, S. M., Moore, M. C., Renner, S., Woods, S. C., Huypens, P., Beckers, J., de Angelis, M. H., Schürmann, A., et al. (2018) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.161 · Cited by 853 · see citing works
Self-citationFulco, M., Cen, Y., Zhao, P., Hoffman, E. P., McBurney, M. W., Sauve, A. A., & Sartorelli, V. (2008) · Developmental Cell · doi:10.1016/j.devcel.2008.02.004 · Cited by 821 · see citing works
Stem cell aging: mechanisms, regulators and therapeutic opportunities
Oh, J., Lee, Y. D., & Wagers, A. J. (2014) · Nature Medicine · doi:10.1038/nm.3651 · Cited by 796 · see citing works
Ristow, M., & Zarse, K. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.03.014 · Cited by 789 · see citing works
Self-citationCoordination of mitophagy and mitochondrial biogenesis during ageing in C. elegans
Palikaras, K., Lionaki, E., & Tavernarakis, N. (2015) · Nature · doi:10.1038/nature14300 · Cited by 770 · see citing works
Speakman, J. R., & Mitchell, S. E. (2011) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2011.07.001 · Cited by 769 · see citing works
Translational Regulation of Gene Expression during Conditions of Cell Stress
Spriggs, K. A., Bushell, M., & Willis, A. E. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.028 · Cited by 721 · see citing works
Extending life span by increasing oxidative stress
Ristow, M., & Schmeisser, S. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.05.010 · Cited by 718 · see citing works
Self-citationMolecular mechanisms of dietary restriction promoting health and longevity
Green, C. L., Lamming, D. W., & Fontana, L. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00411-4 · Cited by 714 · see citing works
Mitochondrial dysfunction in Parkinson's disease
Winklhofer, K. F., & Haass, C. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.08.013 · Cited by 688 · see citing works
Acute exercise and oxidative stress: a 30 year history
Fisher‐Wellman, K. H., & Bloomer, R. J. (2009) · Dynamic Medicine · doi:10.1186/1476-5918-8-1 · Cited by 684 · see citing works
Onken, B., & Driscoll, M. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008758 · Cited by 671 · see citing works
LKB1 and AMP-activated protein kinase control of mTOR signalling and growth
Shaw, R. J. (2009) · Acta Physiologica · doi:10.1111/j.1748-1716.2009.01972.x · Cited by 644 · see citing works
A Mitochondrial Superoxide Signal Triggers Increased Longevity in Caenorhabditis elegans
Yang, W., & Hekimi, S. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000556 · Cited by 630 · see citing works
Yun, J., & Finkel, T. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.01.011 · Cited by 626 · see citing works
Taking a good look at free radicals in the aging process
Hekimi, S., Lapointe, J., & Wen, Y. (2011) · Trends in Cell Biology · doi:10.1016/j.tcb.2011.06.008 · Cited by 606 · see citing works
Replicative and chronological aging in Saccharomyces cerevisiae
Longo, V. D., Shadel, G. S., Kaeberlein, M., & Kennedy, B. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.06.002 · Cited by 595 · see citing works
Mitochondria as signaling organelles
Chandel, N. S. (2014) · BMC Biology · doi:10.1186/1741-7007-12-34 · Cited by 576 · see citing works
Greer, E. L., & Brunet, A. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00459.x · Cited by 574 · see citing works
Mitochondrial dysfunction and oxidative stress in aging and cancer
Kudryavtseva, A. V., Krasnov, G. S., Dmitriev, A. A., Alekseev, B. Y., Kardymon, O. L., Садритдинова, А. Ф., Fedorova, M., Pokrovsky, A. V., Melnikova, N. V., Каприн, А. Д., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.9821 · Cited by 551 · see citing works
Metabolic Regulation of T Cell Longevity and Function in Tumor Immunotherapy
Kishton, R. J., Sukumar, M., & Restifo, N. P. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.06.016 · Cited by 548 · see citing works
Genetics of Longevity in Model Organisms: Debates and Paradigm Shifts
Gems, D., & Partridge, L. (2012) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183712 · Cited by 545 · see citing works
Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS)
Ristow, M., & Schmeisser, K. (2014) · Dose-Response · doi:10.2203/dose-response.13-035.ristow · Cited by 534 · see citing works
Self-citationMitochondrial peroxiredoxin involvement in antioxidant defence and redox signalling
Cox, A. G., Winterbourn, C. C., & Hampton, M. B. (2009) · Biochemical Journal · doi:10.1042/bj20091541 · Cited by 530 · see citing works
Haigis, M. C., & Yankner, B. A. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.10.002 · Cited by 525 · see citing works
Mitochondrial Dysfunction in Cancer
Boland, M. L., Chourasia, A. H., & Macleod, K. F. (2013) · Frontiers in Oncology · doi:10.3389/fonc.2013.00292 · Cited by 502 · see citing works
Stress-Response Hormesis and Aging: “That which Does Not Kill Us Makes Us Stronger”
Gems, D., & Partridge, L. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.01.001 · Cited by 496 · see citing works
Lee, S., Hwang, A. B., & Kenyon, C. J. (2010) · Current Biology · doi:10.1016/j.cub.2010.10.057 · Cited by 495 · see citing works
AMPK at the Nexus of Energetics and Aging
Burkewitz, K., Zhang, Y., & Mair, W. B. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.03.002 · Cited by 483 · see citing works
Mitochondrial oxidative stress in aging and healthspan
Dai, D., Chiao, Y. A., Marcinek, D. J., Szeto, H. H., & Rabinovitch, P. S. (2014) · Longevity & Healthspan · doi:10.1186/2046-2395-3-6 · Cited by 481 · see citing works
Doonan, R., McElwee, J., Matthijssens, F., Walker, G. A., Houthoofd, K., Back, P., Matscheski, A., Vanfleteren, J. R., & Gems, D. (2008) · Genes & Development · doi:10.1101/gad.504808 · Cited by 480 · see citing works
Shields, H. J., Traa, A., & Van Raamsdonk, J. M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.628157 · Cited by 478 · see citing works
Exposure to hydrogen peroxide induces oxidation and activation of AMP-activated protein kinase
Zmijewski, J. W., Banerjee, S., Bae, H., Friggeri, A., Lazarowski, E. R., & Abraham, E. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.143685 · Cited by 441 · see citing works
Zarse, K., Schmeisser, S., Groth, M., Priebe, S., Beuster, G., Kuhlow, D., Guthke, R., Platzer, M., Kahn, C. R., & Ristow, M. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.02.013 · Cited by 430 · see citing works
Self-citationAging, inflammation and the environment
Bektas, A., Schurman, S. H., Sen, R., & Ferrucci, L. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.12.015 · Cited by 431 · see citing works
Unraveling the Truth About Antioxidants: Mitohormesis explains ROS-induced health benefits
Ristow, M. (2014) · Nature Medicine · doi:10.1038/nm.3624 · Cited by 417 · see citing works
Self-citationMuscle Mitohormesis Promotes Longevity via Systemic Repression of Insulin Signaling
Owusu-Ansah, E., Song, W., & Perrimon, N. (2013) · Cell · doi:10.1016/j.cell.2013.09.021 · Cited by 395 · see citing works
Lee, S., Murphy, C. T., & Kenyon, C. J. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.10.003 · Cited by 391 · see citing works
Redox-optimized ROS balance: A unifying hypothesis
Aon, M. A., Cortassa, S. C., & O'Rourke, B. P. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.02.016 · Cited by 376 · see citing works
Mitochondrial dysfunction as a cause of ageing
Trifunović, A., & Larsson, N. (2008) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2007.01905.x · Cited by 375 · see citing works
Mitochondrial ROS produced via reverse electron transport extend animal lifespan
Scialò, F., Sriram, A., Fernández-Ayala, D., Gubina, N., Lõhmus, M., Nelson, G., Logan, A., Cooper, H. M., Navas, P., Enríquez, J. A., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.03.009 · Cited by 371 · see citing works
Interrelation between ROS and Ca2+ in aging and age-related diseases
Madreiter‐Sokolowski, C. T., Thomas, C., & Ristow, M. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101678 · Cited by 365 · see citing works
Self-citationThe role of mitochondrial <scp>ROS</scp> in the aging brain
Stefanatos, R., & Sanz, A. (2018) · FEBS Letters · doi:10.1002/1873-3468.12902 · Cited by 358 · see citing works
Yee, C., Yang, W., & Hekimi, S. (2014) · Cell · doi:10.1016/j.cell.2014.02.055 · Cited by 356 · see citing works
Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2
De Haes, W., Frooninckx, L., Van Assche, R., Smolders, A., Depuydt, G., Billen, J., Braeckman, B. P., Schoofs, L., & Temmerman, L. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1321776111 · Cited by 355 · see citing works
Cardiac Aging: From Molecular Mechanisms to Significance in Human Health and Disease
Dai, D.-F., Chen, T., Johnson, S. C., Szeto, H., & Rabinovitch, P. S. (2012) · Antioxidants & Redox Signaling · doi:10.1089/ars.2011.4179 · Cited by 334 · see citing works
Lessons from C. elegans: signaling pathways for longevity
Lapierre, L. R., & Hansen, M. (2012) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2012.07.007 · Cited by 331 · see citing works
Animal models of aging research: implications for human aging and age-related diseases
Mitchell, S. J., Scheibye-Knudsen, M., Longo, D. L., & de Cabo, R. (2015) · Annual Review of Animal Biosciences · doi:10.1146/annurev-animal-022114-110829 · Cited by 328 · see citing works
The metabolic regulation of aging
Finkel, T. (2015) · Nature Medicine · doi:10.1038/nm.3998 · Cited by 325 · see citing works
ROS signaling and ER stress in cardiovascular disease
Ochoa, C. D., Wu, R. F., & Terada, L. S. (2018) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2018.03.002 · Cited by 324 · see citing works
Caenorhabditis elegans dauers need LKB1/AMPK to ration lipid reserves and ensure long-term survival
Narbonne, P., & Roy, R. (2008) · Nature · doi:10.1038/nature07536 · Cited by 315 · see citing works
Regulation of Yeast Chronological Life Span by TORC1 via Adaptive Mitochondrial ROS Signaling
Pan, Y., Schroeder, E. A., Ocampo, A., Barrientos, A., & Shadel, G. S. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.03.018 · Cited by 313 · see citing works
Egea, J., Fabregat, I., Frapart, Y., Ghezzi, P., Görlach, A., Kietzmann, T., Kubaichuk, K. I., Knaus, U. G., López, M. G., González, G. O., et al. (2017) · Redox Biology · doi:10.1016/j.redox.2017.05.007 · Cited by 311 · see citing works
Kim, K. H., Son, J. M., Benayoun, B. A., & Lee, C. D. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.06.008 · Cited by 311 · see citing works
Bjelaković, G., Nikolova, D., Gluud, L. L., Simonetti, R. G., & Gluud, C. N. (2008) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007176 · Cited by 307 · see citing works
Effect of Antioxidants Supplementation on Aging and Longevity
Sadowska‐Bartosz, I., & Bartosz, G. (2014) · BioMed Research International · doi:10.1155/2014/404680 · Cited by 298 · see citing works
Antioxidant Supplementation in the Treatment of Aging-Associated Diseases
Conti, V., Izzo, V., Corbi, G., Russomanno, G., Manzo, V., Lise, F. D., Donato, A. D., & Filippelli, A. (2016) · Frontiers in Pharmacology · doi:10.3389/fphar.2016.00024 · Cited by 296 · see citing works
ROS homeostasis and metabolism: a critical liaison for cancer therapy
Kim, J., Kim, J., & Bae, J. (2016) · Experimental & Molecular Medicine · doi:10.1038/emm.2016.119 · Cited by 295 · see citing works
Calorie restriction as an intervention in ageing
López‐Lluch, G., & Navas, P. (2015) · The Journal of Physiology · doi:10.1113/jp270543 · Cited by 290 · see citing works
C. elegans as Model for the Study of High Glucose– Mediated Life Span Reduction
Schlotterer, A., Kukudov, G., Bozorgmehr, F., Hutter, H., Du, X., Oikonomou, D., Ibrahim, Y., Pfisterer, F., Rabbani, N., Thornalley, P. J., et al. (2009) · Diabetes · doi:10.2337/db09-0567 · Cited by 289 · see citing works
Strategies for Reducing or Preventing the Generation of Oxidative Stress
Poljšak, B. (2011) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2011/194586 · Cited by 287 · see citing works
Calorie Restriction: Is AMPK a Key Sensor and Effector
Cantó, C., & Auwerx, J. (2011) · Physiology · doi:10.1152/physiol.00010.2011 · Cited by 282 · see citing works
The sirtuins, oxidative stress and aging: an emerging link
Merksamer, P. I., Liu, Y., He, W., Hirschey, M. D., Chen, D., & Verdin, E. (2013) · Aging · doi:10.18632/aging.100544 · Cited by 275 · see citing works
The role of mitochondrial DNA mutations and free radicals in disease and ageing
Lagouge, M., & Larsson, N. (2013) · Journal of Internal Medicine · doi:10.1111/joim.12055 · Cited by 270 · see citing works
Mitochondrial energy metabolism and ageing
Bratic, I., & Trifunović, A. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.01.004 · Cited by 268 · see citing works
Mesquita, A., Weinberger, M., Silva, A., Sampaio‐Marques, B., Almeida, B., Leão, C., Costa, V., Rodrigues, F. J. S., Burhans, W. C., & Ludovico, P. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1004432107 · Cited by 268 · see citing works
FoxO proteins restrain osteoclastogenesis and bone resorption by attenuating H2O2 accumulation
Bartell, S. M., Kim, H., Ambrogini, E., Li, H., Iyer, S. V., Ucer, S., Rabinovitch, P. S., Jilka, R. L., Weinstein, R. S., Zhao, H., et al. (2014) · Nature Communications · doi:10.1038/ncomms4773 · Cited by 267 · see citing works
Lipid and Carbohydrate Metabolism in Caenorhabditis elegans
Watts, J. L., & Ristow, M. (2017) · Genetics · doi:10.1534/genetics.117.300106 · Cited by 263 · see citing works
Self-citationWhen a theory of aging ages badly
Lapointe, J., & Hekimi, S. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0138-8 · Cited by 261 · see citing works
Mitochondrial Dysfunction in Alzheimer’s Disease and the Rationale for Bioenergetics Based Therapies
Onyango, I. G., Dennis, J., & Khan, S. M. (2016) · Aging and Disease · doi:10.14336/ad.2015.1007 · Cited by 260 · see citing works
Bouitbir, J., Charles, A.-L., Echaniz-Laguna, A., Kindo, M., Daussin, F., Auwerx, J., Piquard, F., Geny, B., & Zoll, J. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehr224 · Cited by 256 · see citing works
Mitochondrial redox signalling at a glance
Collins, Y., Chouchani, E. T., James, A. M., Menger, K. E., Cochemé, H. M., & Murphy, M. P. (2012) · Journal of Cell Science · doi:10.1242/jcs.098475 · Cited by 255 · see citing works
Inflammageing and metaflammation: The yin and yang of type 2 diabetes
Prattichizzo, F., Nigris, V. D., Spiga, R., Mancuso, E., Sala, L. L., Antonicelli, R., Testa, R., Procopio, A. D., Olivieri, F., & Ceriello, A. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.10.003 · Cited by 249 · see citing works
Mitochondrial dysfunction and longevity in animals: Untangling the knot
Wang, Y., & Hekimi, S. (2015) · Science · doi:10.1126/science.aac4357 · Cited by 248 · see citing works
Merry, T. L., & Ristow, M. (2016) · The Journal of Physiology · doi:10.1113/jp271957 · Cited by 246 · see citing works
Self-citation
- 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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