Requirement of NAD and SIR2 for Life-Span Extension by Calorie Restriction in Saccharomyces cerevisiae
Abstract
Calorie restriction extends life-span in a wide variety of organisms. Although it has been suggested that calorie restriction may work by reducing the levels of reactive oxygen species produced during respiration, the mechanism by which this regimen slows aging is uncertain. Here, we mimicked calorie restriction in yeast by physiological or genetic means and showed a substantial extension in life-span. This extension was not observed in strains mutant for SIR2 (which encodes the silencing protein Sir2p) or NPT1 (a gene in a pathway in the synthesis of NAD, the oxidized form of nicotinamide adenine dinucleotide). These findings suggest that the increased longevity induced by calorie restriction requires the activation of Sir2p by NAD.
Integrity signals
Registry
Cites
Statistics
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?
SIR2, an NAD+-dependent deacetylase, was among the first genes linked to the response to caloric restriction, initially in yeast.
“The NAD+-dependent deacetylase SIR2 was one of the earliest genes to be implicated in the response to caloric restriction, initially in a yeast model (81).”
From Neural mechanisms of ageing and cognitive decline (2010) · cites this paper as [81]
Sir2 activity ties the energy status of the yeast cell to longevity.
“It has been proposed that Sir2 activity ties the energy status of the yeast cell to longevity (Blander and Guarente, 2004; Lin et al., 2000”
From DNA Repair, Genome Stability, and Aging (2005) · cites this paper as Lin et al., 2000
Caloric restriction is an intervention capable of extending life span in many different organisms from yeast to mammals.
“an intervention capable of extending life span in many different organisms from yeast to mammals (Cohen et al., 2004; Howitz et al., 2003; Lin et al., 2000; Rogina and Helfand, 2004; Wood et al., 2004”
From DNA Repair, Genome Stability, and Aging (2005) · cites this paper as Lin et al., 2000
Different situations of energy restriction, including fasting and exercise, increase NAD+ levels and trigger SIRT1/PGC-1α-dependent mitochondrial adaptation.
“Indeed, different situations of energy restriction, including fasting and exercise, increase NAD+ levels and trigger SIRT1/PGC-1α-dependent mitochondrial adaptation (Lin et al, 2000; Houtkooper et al, 2012).”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Lin et al, 2000
Cites
Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
Imai, S.-I., Armstrong, C. M., Kaeberlein, M., & Guarente, L. (2000) · Nature · doi:10.1038/35001622 · Cited by 3,510 · see citing works
Self-citationOxidative Stress, Caloric Restriction, and Aging
Sohal, R. S., & Weindruch, R. H. (1996) · Science · doi:10.1126/science.273.5271.59 · Cited by 3,133 · see citing works
Kaeberlein, M., McVey, M., & Guarente, L. (1999) · Genes & Development · doi:10.1101/gad.13.19.2570 · Cited by 2,253 · see citing works
Self-citationA new efficient gene disruption cassette for repeated use in budding yeast
Güldener, U. (1996) · Nucleic Acids Research · doi:10.1093/nar/24.13.2519 · Cited by 1,657 · see citing works
Extrachromosomal rDNA circles—a cause of aging in yeast
Sinclair, D. A., & Guarente, L. (1997) · Cell · doi:10.1016/s0092-8674(00)80493-6 · Cited by 1,500 · see citing works
Self-citationGene expression profile of aging and its retardation by caloric restriction
Lee, C.-K., Klopp, R. G., Weindruch, R., & Prolla, T. A. (1999) · Science · doi:10.1126/science.285.5432.1390 · Cited by 1,473 · see citing works
The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases
Landry, J., Sutton, A., Tafrov, S. T., Heller, R. C., Stebbins, J., Pillus, L., & Sternglanz, R. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.110148297 · Cited by 970 · see citing works
Function and Regulation of Yeast Hexose Transporters
Özcan, S., & Johnston, M. (1999) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.63.3.554-569.1999 · Cited by 729 · see citing works
Smith, J. S., Brachmann, C. B., Celic, I., Kenna, M. A., Muhammad, S., Starai, V. J., Avalos, J. L., Escalante-Semerena, J. C., Grubmeyer, C., Wolberger, C., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.12.6658 · Cited by 718 · see citing works
Thevelein, J. M., & WINDE, J. H. D. (1999) · Molecular Microbiology · doi:10.1046/j.1365-2958.1999.01538.x · Cited by 682 · see citing works
Elimination of Replication Block Protein Fob1 Extends the Life Span of Yeast Mother Cells
Defossez, P., Prusty, R., Kaeberlein, M. R., Lin, S.-J., Ferrigno, P. K., Silver, P. A., Keil, R., & Guarente, L. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80472-4 · Cited by 401 · see citing works
Self-citationSmith, A., Ward, M. P., & Garrett, S. (1998) · The EMBO Journal · doi:10.1093/emboj/17.13.3556 · Cited by 364 · see citing works
Colombo, S., Ma, P., Cauwenberg, L., Winderickx, J., Crauwels, M., Teunissen, A. W. R. H., Nauwelaers, D., de Winde, J. H., Gorwa‐Grauslund, M. F., Colavizza, D., et al. (1998) · The EMBO Journal · doi:10.1093/emboj/17.12.3326 · Cited by 306 · see citing works
Xue, Y., Batlle, M., & Hirsch, J. P. (1998) · The EMBO Journal · doi:10.1093/emboj/17.7.1996 · Cited by 306 · see citing works
Yeast Heterochromatin: Regulation of Its Assembly and Inheritance by Histones
Grunstein, M. (1998) · Cell · doi:10.1016/s0092-8674(00)81160-5 · Cited by 290 · see citing works
RAS genes in Saccharomyces cerevisiae: signal transduction in search of a pathway
Broach, J. R. (1991) · Trends in Genetics · doi:10.1016/0168-9525(91)90018-l · Cited by 209 · see citing works
Calorie Restriction in Primates: Will It Work and How Will We Know?
Roth, G. S., Ingram, D. K., & Lane, M. A. (1999) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1999.tb03851.x · Cited by 184 · see citing works
Calendar life span versus budding lifespan of Saccharomyces cerevisiae
Müller, I., Zimmermann, M., Becker, D., & Flömer, M. (1980) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(80)90028-7 · Cited by 169 · see citing works
Diverse and dynamic functions of the Sir silencing complex
Guarente, L. (1999) · Nature Genetics · doi:10.1038/15458 · Cited by 154 · see citing works
Self-citationModulation of aging processes by dietary restriction
Yu, B. P. (1994) · CRC Press eBooks · Cited by 143 · see citing works
Cloning of genes that complement yeast hexokinase and glucokinase mutants
Walsh, R. B., Kawasaki, G., & Fraenkel, D. G. (1983) · Journal of Bacteriology · doi:10.1128/jb.154.2.1002-1004.1983 · Cited by 55 · see citing works
Rajavel, M., Lalo, D., Gross, J. W., & Grubmeyer, C. T. (1998) · Biochemistry · doi:10.1021/bi9720134 · Cited by 30 · see citing works
[2] Energy coupling through molecular discrimination: Nicotinate phosphoribosyltransferase
Grubmeyer, C. T., Gross, J. W., & Rajavel, M. (1999) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(99)08004-0 · Cited by 22 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Lagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H., Lerin, C., Daussin, F., Messadeq, N., Milne, J., Lambert, P., Elliott, P., et al. (2006) · Cell · doi:10.1016/j.cell.2006.11.013 · Cited by 4,057 · see citing works
Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
Howitz, K. T., Bitterman, K. J., Cohen, H. Y., Lamming, D. W., Lavu, S., Wood, J. G., Zipkin, R. E., Chung, P., Kisielewski, A., Zhang, L.-L., et al. (2003) · Nature · doi:10.1038/nature01960 · Cited by 3,796 · see citing works
Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase
Brunet, A., Sweeney, L. B., Sturgill, J. F., Chua, K. F., Greer, P. L., Lin, Y., Tran, H., Ross, S. E., Mostoslavsky, R., Cohen, H. Y., et al. (2004) · Science · doi:10.1126/science.1094637 · Cited by 3,239 · see citing works
Extending Healthy Life Span—From Yeast to Humans
Fontana, L., Partridge, L., & Longo, V. D. (2010) · Science · doi:10.1126/science.1172539 · Cited by 3,023 · see citing works
Mammalian Sirtuins: Biological Insights and Disease Relevance
Haigis, M. C., & Sinclair, D. A. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathol.4.110807.092250 · Cited by 2,085 · see citing works
Negative Control of p53 by Sir2α Promotes Cell Survival under Stress
Luo, J., Nikolaev, A. Y., Imai, S.-I., Chen, D., Su, F., Shiloh, A., Guarente, L., & Gu, W. (2001) · Cell · doi:10.1016/s0092-8674(01)00524-4 · Cited by 2,081 · see citing works
Self-citationSirt1 promotes fat mobilization in white adipocytes by repressing PPAR-γ
Picard, F., Kurtev, M. V., Chung, N., Topark‐Ngarm, A., Senawong, T., de Oliveira, R. M., Leid, M. E., McBurney, M. W., & Guarente, L. (2004) · Nature · doi:10.1038/nature02583 · Cited by 1,943 · see citing works
Self-citationCalorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase
Cohen, H. Y., Miller, C., Bitterman, K. J., Wall, N. R., Hekking, B., Kessler, B., Howitz, K. T., Gorospe, M., de Cabo, R., & Sinclair, D. A. (2004) · Science · doi:10.1126/science.1099196 · Cited by 1,924 · 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
Self-citationSirtuin activators mimic caloric restriction and delay ageing in metazoans
Wood, J. G., Rogina, B., Lavu, S., Howitz, K., Helfand, S. L., Tatar, M., & Sinclair, D. (2004) · Nature · doi:10.1038/nature02789 · Cited by 1,868 · see citing works
Sirtuins in mammals: insights into their biological function
Michán, S., & Sinclair, D. A. (2007) · Biochemical Journal · doi:10.1042/bj20070140 · Cited by 1,719 · see citing works
Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes
Milne, J. C., Lambert, P. D., Schenk, S., Carney, D. P., Smith, J. J., Gagne, D. J., Jin, L., Boss, O., Perni, R. B., Vu, C. B., et al. (2007) · Nature · doi:10.1038/nature06261 · Cited by 1,707 · see citing works
Induction of autophagy by spermidine promotes longevity
Eisenberg, T., Knauer, H., Schauer, A., Büttner, S., Ruckenstuhl, C., Carmona-Gutierrez, D., Ring, J., Schroeder, S., Magnes, C., Antonacci, L., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1975 · Cited by 1,680 · see citing works
The Sir2 Family of Protein Deacetylases
Blander, G., & Guarente, L. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.073651 · Cited by 1,496 · see citing works
Self-citationNAD+ and sirtuins in aging and disease
Imai, S.-I., & Guarente, L. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.04.002 · Cited by 1,481 · see citing works
Self-citationA role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy
Lee, I. H., Cao, L., Mostoslavsky, R., Lombard, D. B., Liu, J., Bruns, N. E., Tsokos, M., Alt, F. W., & Finkel, T. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712145105 · Cited by 1,473 · see citing works
From discoveries in ageing research to therapeutics for healthy ageing
Campisi, J., Kapahi, P., Lithgow, G. J., Melov, S., Newman, J. C., & Verdin, E. (2019) · Nature · doi:10.1038/s41586-019-1365-2 · Cited by 1,389 · see citing works
Sir2 mediates longevity in the fly through a pathway related to calorie restriction
Rogina, B., & Helfand, S. L. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404184101 · Cited by 1,361 · see citing works
Mammalian SIRT1 Represses Forkhead Transcription Factors
Motta, M. C., Divecha, N., Lemieux, M. E., Kamel, C., Chen, D., Gu, W. J., Bultsma, Y., McBurney, M. W., & Guarente, L. (2004) · Cell · doi:10.1016/s0092-8674(04)00126-6 · Cited by 1,351 · see citing works
Self-citationNeural mechanisms of ageing and cognitive decline
Bishop, N. A., Lu, T., & Yankner, B. A. (2010) · Nature · doi:10.1038/nature08983 · Cited by 1,323 · see citing works
Resveratrol Ameliorates Aging-Related Metabolic Phenotypes by Inhibiting cAMP Phosphodiesterases
Park, S. J., Ahmad, F., Philp, A., Baar, K., Williams, T., Luo, H., Ke, H., Rehmann, H., Taussig, R., Brown, A. L., et al. (2012) · Cell · doi:10.1016/j.cell.2012.01.017 · Cited by 1,352 · see citing works
Genetic pathways that regulate ageing in model organisms
Guarente, L., & Kenyon, C. J. (2000) · Nature · doi:10.1038/35041700 · Cited by 1,337 · see citing works
Self-citationNAD <sup>+</sup> in aging, metabolism, and neurodegeneration
Verdin, E. (2015) · Science · doi:10.1126/science.aac4854 · Cited by 1,319 · see citing works
Timmers, S., Konings, E., Bilet, L., Houtkooper, R. H., van de Weijer, T., Goossens, G. H., Hoeks, J., van der Krieken, S., Ryu, D., Kersten, S., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.10.002 · Cited by 1,320 · see citing works
Regulation of Yeast Replicative Life Span by TOR and Sch9 in Response to Nutrients
Kaeberlein, M., Powers, R. W., Steffen, K. K., Westman, E. A., Hu, D., Dang, N., Kerr, E. O., Kirkland, K. T., Fields, S., & Kennedy, B. K. (2005) · Science · doi:10.1126/science.1115535 · Cited by 1,293 · 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
Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction
Haigis, M. C., & Guarente, L. P. (2006) · Genes & Development · doi:10.1101/gad.1467506 · Cited by 1,295 · see citing works
Self-citationMetabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC‐1α
Gerhart‐Hines, Z., Rodgers, J. T., Bare, O., Lerin, C., Kim, S., Mostoslavsky, R., Alt, F. W., Wu, Z., & Puigserver, P. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601633 · Cited by 1,294 · see citing works
Schulz, T. J., Zarse, K., Voigt, A., Urban, N., Birringer, M., & Ristow, M. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.08.011 · Cited by 1,209 · see citing works
Sugar Sensing and Signaling in Plants
Rolland, F., Moore, B. D., & Sheen, J. (2002) · The Plant Cell · doi:10.1105/tpc.010455 · Cited by 1,177 · see citing works
Haigis, M. C., Mostoslavsky, R., Haigis, K. M., Fahie, K., Christodoulou, D. C., Murphy, A. J., Valenzuela, D. M., Yancopoulos, G. D., Karow, M., Blander, G., et al. (2006) · Cell · doi:10.1016/j.cell.2006.06.057 · Cited by 1,162 · see citing works
Self-citationSomeya, S., Yu, W., Hallows, W. C., Xu, J., Vann, J. M., Leeuwenburgh, C., Tanokura, M., Denu, J. M., & Prolla, T. A. (2010) · Cell · doi:10.1016/j.cell.2010.10.002 · Cited by 1,150 · see citing works
Pearson, K. J., Baur, J. A., Lewis, K. N., Peshkin, L., Price, N. L., Labinskyy, N., Swindell, W. R., Kamara, D., Minor, R. K., Perez, E., et al. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.06.011 · Cited by 1,162 · see citing works
Sirt1 Regulates Aging and Resistance to Oxidative Stress in the Heart
Alcendor, R. R., Gao, S., Zhai, P., Zablocki, D., Holle, E., Yu, X., Tian, B., Wagner, T., Vatner, S. F., & Sadoshima, J. (2007) · Circulation Research · doi:10.1161/01.res.0000267723.65696.4a · Cited by 1,147 · see citing works
SIRT1 and other sirtuins in metabolism
Chang, H.-C., & Guarente, L. (2014) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2013.12.001 · Cited by 1,138 · see citing works
Self-citationDynamic FoxO transcription factors
Huang, H., & Tindall, D. J. (2007) · Journal of Cell Science · doi:10.1242/jcs.001222 · Cited by 1,106 · see citing works
Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS
Nisoli, E., Tonello, C., Cardile, A., Cozzi, V., Bracale, R., Tedesco, L., Falcone, S., Valerio, A., Cantoni, O., Clementi, E., et al. (2005) · Science · doi:10.1126/science.1117728 · Cited by 1,107 · see citing works
Kim, D., Nguyen, M. D., Dobbin, M. M., Fischer, A., Sananbenesi, F., Rodgers, J. T., Delalle, I., Baur, J. A., Sui, G., Armour, S. M., et al. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601758 · Cited by 1,074 · 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
Self-citationNAD+ metabolism: pathophysiologic mechanisms and therapeutic potential
Xie, N., Zhang, L., Gao, W. Q., Huang, C., Huber, P., Zhou, X., Li, C. L., Shen, G., & Zou, B. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00311-7 · Cited by 1,076 · see citing works
Overview of caloric restriction and ageing
Masoro, E. J. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2005.03.012 · Cited by 1,054 · see citing works
SIRT1 Functionally Interacts with the Metabolic Regulator and Transcriptional Coactivator PGC-1α
Nemoto, S., Fergusson, M. M., & Finkel, T. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501485200 · Cited by 1,047 · see citing works
Calorie restriction, SIRT1 and metabolism: understanding longevity
Bordone, L., & Guarente, L. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1616 · Cited by 1,021 · see citing works
Self-citationRevollo, J. R., Grimm, A. A., & Imai, S.-I. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m408388200 · Cited by 1,010 · see citing works
Bitterman, K. J., Anderson, R. M., Cohen, H. Y., Latorre-Esteves, M., & Sinclair, D. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205670200 · Cited by 1,002 · see citing works
Extension of Chronological Life Span in Yeast by Decreased TOR Pathway Signaling
Powers, R. W., Kaeberlein, M., Caldwell, S. D., Kennedy, B. K., & Fields, S. (2006) · Genes & Development · doi:10.1101/gad.1381406 · Cited by 982 · see citing works
NAD+ metabolism in health and disease
Belenky, P. A., Bogan, K. L., & Brenner, C. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2006.11.006 · Cited by 983 · see citing works
Modulation of cellular processes by histone and non-histone protein acetylation
Shvedunova, M., & Akhtar, A. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00441-y · Cited by 975 · see citing works
Nutrient-Sensitive Mitochondrial NAD+ Levels Dictate Cell Survival
Yang, H., Yang, T., Baur, J. A., Perez, E., Matsui, T., Carmona, J. J., Lamming, D. W., Souza-Pinto, N. C., Bohr, V. A., Rosenzweig, A., et al. (2007) · Cell · doi:10.1016/j.cell.2007.07.035 · Cited by 950 · see citing works
DNA Repair, Genome Stability, and Aging
Lombard, D. B., Chua, K. F., Mostoslavsky, R., Franco, S., Gostissa, M., & Alt, F. W. (2005) · Cell · doi:10.1016/j.cell.2005.01.028 · Cited by 944 · see citing works
AMPK and SIRT1: a long-standing partnership?
Ruderman, N. B., Julia Xu, X., Nelson, L., Cacicedo, J. M., Saha, A. K., Lan, F., & Ido, Y. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00745.2009 · Cited by 903 · see citing works
The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways
Houtkooper, R. H., Cantó, C., Wanders, R. J., & Auwerx, J. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0026 · Cited by 899 · see citing works
Butow, R. A., & Avadhani, N. G. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00179-0 · Cited by 882 · see citing works
Regulation of Longevity and Stress Resistance by Sch9 in Yeast
Fabrizio, P., Pozza, F., Pletcher, S. D., Gendron, C. M., & Longo, V. D. (2001) · Science · doi:10.1126/science.1059497 · Cited by 874 · see citing works
Human SIR2 deacetylates p53 and antagonizes PML/p53‐induced cellular senescence
Langley, E., Pearson, M., Faretta, M., Bauer, U., Frye, R. A., Minucci, S., Pelicci, P. G., & Kouzarides, T. (2002) · The EMBO Journal · doi:10.1093/emboj/21.10.2383 · Cited by 859 · see citing works
Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds
Bonkowski, M. S., & Sinclair, D. A. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.93 · Cited by 834 · see citing works
Hara, Y., Wakamori, M., Ishii, M., Maeno, E., Nishida, M., Yoshida, T., Yamada, H., Shimizu, S., Mori, E., Kudoh, J., et al. (2002) · Molecular Cell · doi:10.1016/s1097-2765(01)00438-5 · Cited by 816 · see citing works
Fulco, 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
The Critical Role of Metabolic Pathways in Aging
Barzilai, N., Huffman, D. M., Muzumdar, R. H., & Bartke, A. (2012) · Diabetes · doi:10.2337/db11-1300 · Cited by 803 · see citing works
Calorie restriction–the SIR2 connection
Guarente, L., & Picard, F. (2005) · Cell · doi:10.1016/j.cell.2005.01.029 · Cited by 793 · see citing works
Self-citationRistow, M., & Zarse, K. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.03.014 · Cited by 789 · see citing works
Calorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans
Civitarese, A. E., Carling, S., Heilbronn, L. K., Hulver, M. H., Ukropcova, B., Deutsch, W. A., Smith, S. R., & Ravussin, E. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040076 · Cited by 790 · see citing works
Bieganowski, P., & Brenner, C. (2004) · Cell · doi:10.1016/s0092-8674(04)00416-7 · Cited by 750 · see citing works
Nucleocytoplasmic Shuttling of the NAD+-dependent Histone Deacetylase SIRT1*
Tanno, M., Sakamoto, J., Miura, T., Shimamoto, K., & Horio, Y. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m609554200 · Cited by 784 · see citing works
Molecular 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
Sirtuin 1 Modulates Cellular Responses to Hypoxia by Deacetylating Hypoxia-Inducible Factor 1α
Lim, J.-H., Lee, Y.-M., Chun, Y.-S., Chen, J., Kim, J.-E., & Park, J.-W. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.023 · Cited by 758 · see citing works
Substrate-specific activation of sirtuins by resveratrol
Kaeberlein, M., McDonagh, T., Heltweg, B., Hixon, J., Westman, E. A., Caldwell, S. D., Napper, A., Curtis, R., DiStefano, P. S., Fields, S., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500655200 · Cited by 745 · see citing works
Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae
Anderson, R. M., Bitterman, K. J., Wood, J. G., Medvedik, O., & Sinclair, D. A. (2003) · Nature · doi:10.1038/nature01578 · Cited by 736 · see citing works
The Establishment, Inheritance, and Function of Silenced Chromatin in Saccharomyces cerevisiae
Rusché, L. N., Kirchmaier, A. L., & Rine, J. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161547 · Cited by 726 · 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
Sirtuin 1 and Sirtuin 3: Physiological Modulators of Metabolism
Nogueiras, R., Habegger, K. M., Chaudhary, N., Finan, B., Banks, A. S., Dietrich, M. O., Horváth, T. L., Sinclair, D. A., Pfluger, P. T., & Tschöp, M. H. (2012) · Physiological Reviews · doi:10.1152/physrev.00022.2011 · Cited by 712 · see citing works
Schwer, B., Bunkenborg, J., Verdin, R. O., Andersen, J. S., & Verdin, E. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603968103 · Cited by 705 · see citing works
Sirt1 Regulates Insulin Secretion by Repressing UCP2 in Pancreatic β Cells
Bordone, L., Motta, M. C., Picard, F., Robinson, A., Jhala, U. S., Apfeld, J., McDonagh, T., Lemieux, M., McBurney, M., Szilvasi, A., et al. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0040031 · Cited by 715 · see citing works
Self-citationShi, T., Wang, F., Stieren, E., & Tong, Q. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414670200 · Cited by 712 · see citing works
Resveratrol as an anti-inflammatory and anti-aging agent: Mechanisms and clinical implications
Alarcón‐de‐la‐Lastra, C., & Villegas, I. (2005) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200500022 · Cited by 705 · see citing works
Metabolic Regulation of Epigenetics
Lu, C., & Thompson, C. B. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.06.001 · Cited by 699 · see citing works
Stem cells, ageing and the quest for immortality
Rando, T. A. (2006) · Nature · doi:10.1038/nature04958 · Cited by 695 · see citing works
Mitochondrial retrograde signaling
Liu, Z., & Butow, R. A. (2006) · Annual Review of Genetics · doi:10.1146/annurev.genet.40.110405.090613 · Cited by 680 · see citing works
Nutrient Availability Regulates SIRT1 Through a Forkhead-Dependent Pathway
Nemoto, S., Fergusson, M. M., & Finkel, T. (2004) · Science · doi:10.1126/science.1101731 · Cited by 671 · see citing works
Onken, B., & Driscoll, M. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008758 · Cited by 671 · see citing works
SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction
Wang, F., Nguyen, M., Qin, F. X.-F., & Tong, Q. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00304.x · Cited by 652 · see citing works
The effects of aging in the hippocampus and cognitive decline
Bettio, L. E. B., Rajendran, L., & Gil‐Mohapel, J. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.04.030 · Cited by 654 · see citing works
Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome
Hebert, A. S., Dittenhafer-Reed, K. E., Yu, W., Bailey, D. J., Selen, E. S., Boersma, M. D., Carson, J. J., Tonelli, M., Balloon, A. J., Higbee, A. J., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2012.10.024 · Cited by 636 · see citing works
Regulation of SIRT1 in cellular functions: Role of polyphenols
Chung, S., Yao, H., Caito, S. W., Hwang, J., Arunachalam, G., & Rahman, I. (2010) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2010.05.003 · Cited by 651 · see citing works
Tumor Suppressor HIC1 Directly Regulates SIRT1 to Modulate p53-Dependent DNA-Damage Responses
Chen, W., Wang, D. H., Yen, R.-W. C., Luo, J., Gu, W. J., & Baylin, S. B. (2005) · Cell · doi:10.1016/j.cell.2005.08.011 · Cited by 649 · see citing works
Calorie restriction extends yeast life span by lowering the level of NADH
Lin, S.-J., Ford, E., Haigis, M., Liszt, G., & Guarente, L. (2004) · Genes & Development · doi:10.1101/gad.1164804 · Cited by 632 · see citing works
Self-citationKume, S., Uzu, T., Horiike, K., Chin-Kanasaki, M., Isshiki, K., Araki, S.-I., Sugimoto, T., Haneda, M., Kashiwagi, A., & Koya, D. (2010) · Journal of Clinical Investigation · doi:10.1172/jci41376 · Cited by 640 · see citing works
SIRT1 Deacetylates and Positively Regulates the Nuclear Receptor LXR
Li, X., Zhang, S., Blander, G., Tse, J. G., Krieger, M., & Guarente, L. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.07.032 · Cited by 631 · see citing works
Self-citationMoynihan, K. A., Grimm, A. A., Plueger, M. M., Bernal‐Mizrachi, E., Ford, E. L., CRAS-MÉNEUR, C. M. H., Permutt, M. A., & Imai, S. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.07.001 · Cited by 630 · see citing works
Schieke, S. M., Phillips, D., McCoy, J. P., Aponte, A. M., Shen, R.-F., Balaban, R. S., & Finkel, T. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603536200 · Cited by 623 · see citing works
Sirtuins in aging and age-related disease
Longo, V. D., & Kennedy, B. K. (2006) · Cell · doi:10.1016/j.cell.2006.07.002 · Cited by 628 · see citing works
Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila
Burnett, C., Valentini, S., Cabreiro, F., Goss, M., Somogyvári, M., Piper, M. D., Hoddinott, M., Sutphin, G. L., Leko, V., McElwee, J. J., et al. (2011) · Nature · doi:10.1038/nature10296 · Cited by 624 · see citing works
A PUF family portrait: 3′UTR regulation as a way of life
Wickens, M., Bernstein, D. S., Kimble, J. E., & Parker, R. (2002) · Trends in Genetics · doi:10.1016/s0168-9525(01)02616-6 · Cited by 615 · see citing works
The Mammalian SIR2α Protein Has a Role in Embryogenesis and Gametogenesis
McBurney, M. W., Yang, X., Jardine, K., Hixon, M., Boekelheide, K., Webb, J. R., Lansdorp, P. M., & Lemieux, M. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.1.38-54.2003 · Cited by 611 · see citing works
Raffaghello, L., Lee, C., Safdie, F. M., Wei, M., Madia, F., Bianchi, G., & Longo, V. D. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708100105 · Cited by 587 · see citing works
Daitoku, H., Hatta, M., Matsuzaki, H., Aratani, S., Ohshima, T., Miyagishi, M., Nakajima, T., & Fukamizu, A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400593101 · Cited by 602 · see citing works
Aging and Survival: The Genetics of Life Span Extension by Dietary Restriction
Mair, W. B., & Dillin, A. G. (2008) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.77.061206.171059 · Cited by 600 · see citing works
Schwer, B., North, B. J., Frye, R. A., Ott, M., & Verdin, E. M. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200205057 · Cited by 599 · 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
Modulation of mammalian life span by the short isoform of p53
Maier, B., Gluba, W., Bernier, B., Turner, T., Mohammad, K., Guise, T., Sutherland, A., Thorner, M., & Scrable, H. (2004) · Genes & Development · doi:10.1101/gad.1162404 · Cited by 586 · see citing works
- Authors
- Lin, S.-J., Defossez, P.-A., & Guarente, L.
- Affiliations
- Massachusetts Institute of Technology (US)
- Venue
- Science
- Published
- 2000-09-22
- Volume
- 289
- Issue
- 5487
- Pages
- 2126-2128
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1987738803
- Cited by
- 1,775
- References
- 23
- Citations by year
- 2026: 19 · 2025: 19 · 2024: 36 · 2023: 35 · 2022: 38 · 2021: 48 · 2020: 51 · 2019: 50 · 2018: 64 · 2017: 58 · 2016: 67 · 2015: 72 · 2014: 77 · 2013: 92 · 2012: 90
- FWCI
- 18.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5f32ag005857-02)
- National Institute on Aging (5-F32-AG05857-02)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- caloric restriction, lifespan extension, aging, NAD+, Sir2, Sir2p, Saccharomyces cerevisiae, reactive oxygen species, longevity
- MeSH terms
- Energy Intake, DNA, Circular, DNA, Fungal, DNA, Ribosomal, Enzyme Activation, Glucose, Histone Deacetylases, Longevity, Mutation, NAD, Pentosyltransferases, Recombination, Genetic, Saccharomyces cerevisiae, Trans-Activators, Cyclic AMP-Dependent Protein Kinases, Gene Silencing, Sirtuins, Silent Information Regulator Proteins, Saccharomyces cerevisiae, Sirtuin 2
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
