The DOI matches its Crossref record; 51 of the 52 references it cites were found in a registry or an index.
The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms
Open accessAbstract
The SIR genes are determinants of life span in yeast mother cells. Here we show that life span regulation by the Sir proteins is independent of their role in nonhomologous end joining. The short life span of a sir3 or sir4 mutant is due to the simultaneous expression of a and alpha mating-type information, which indirectly causes an increase in rDNA recombination and likely increases the production of extrachromosomal rDNA circles. The short life span of a sir2 mutant also reveals a direct failure to repress recombination generated by the Fob1p-mediated replication block in the rDNA. Sir2p is a limiting component in promoting yeast longevity, and increasing the gene dosage extends the life span in wild-type cells. A possible role of the conserved SIR2 in mammalian aging is discussed.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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
“Loss of Sir2 increases rDNA recombination and shortens life span; whereas an extra genomic copy of Sir2, which increases rDNA stability, extends life span (Kaeberlein et al., 1999”
From DNA Repair, Genome Stability, and Aging (2005) · cites this paper as Kaeberlein et al., 1999
In the citing paper
“Loss of Sir2 increases rDNA recombination and shortens life span; whereas an extra genomic copy of Sir2, which increases rDNA stability, extends life span (Kaeberlein et al., 1999”
From DNA Repair, Genome Stability, and Aging (2005) · cites this paper as Kaeberlein et al., 1999
In the citing paper
“Furthermore, increasing the level of Sir2 in yeast increases lifespan (Kaeberlein et al., 1999).”
From The Aging Epigenome (2016) · cites this paper as Kaeberlein et al., 1999
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Sikorski, R. S., & Hieter, P. (1989) · Genetics · doi:10.1093/genetics/122.1.19 · Cited by 8,590
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
Self-citationPosition effect at S. cerevisiae telomeres: Reversible repression of Pol II transcription
Gottschling, D. E., Aparicio, O. M., Billington, B. L., & Zakian, V. A. (1990) · Cell · doi:10.1016/0092-8674(90)90141-z · Cited by 1,325
Johnson, F. B., Sinclair, D. A., & Guarente, L. (1999) · Cell · doi:10.1016/s0092-8674(00)80567-x · Cited by 844
Self-citationRine, J., & Herskowitz, I. (1987) · Genetics · doi:10.1093/genetics/116.1.9 · Cited by 704
Aparicio, O. M., Billington, B. L., & Gottschling, D. E. (1991) · Cell · doi:10.1016/0092-8674(91)90049-5 · Cited by 697
Boulton, S. J., & Jackson, S. P. (1998) · The EMBO Journal · doi:10.1093/emboj/17.6.1819 · Cited by 641
Moore, J. K., & Haber, J. E. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.5.2164 · Cited by 623
An unusual form of transcriptional silencing in yeast ribosomal DNA.Preprint
Smith, J. S., & Boeke, J. D. (1997) · Genes & Development · doi:10.1101/gad.11.2.241 · Cited by 588
DNA end-joining: from yeast to man
Critchlow, S. E., & Jackson, S. P. (1998) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(98)01284-5 · Cited by 584
Cited by
Sorted by citations
Items 901–1,000 of 1,004
Banerjee, K. K., Ayyub, C., Sengupta, S., & Kolthur‐Seetharam, U. (2012) · Aging · doi:10.18632/aging.100435 · Cited by 54
“and its dependence on NAD+ for its activity is crucial for its ability to link calorie/dietary restriction (CR/DR) with lifespan extension [18, 19].”
BackgroundSIRT1 and caloric restriction: an insight into possible trade-offs between robustness and frailty
Imai, S. (2009) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e32832c932d · Cited by 55
Opposing roles of Ubp3‐dependent deubiquitination regulate replicative life span and heat resistance
Öling, D., Eisele, F., Kvint, K., & Nyström, T. (2014) · The EMBO Journal · doi:10.1002/embj.201386822 · Cited by 54
“A micromanipulator (Singer instruments) was used to remove daughters from mother cells (Kaeberlein et al , 1999).”
Amyloids and Yeast Prion Biology
Wickner, R. B., Edskes, H. K., Bateman, D. A., Kelly, A. C., Gorkovskiy, A., Dayani, Y., & Zhou, A. E. (2013) · Biochemistry · doi:10.1021/bi301686a · Cited by 55
A New Splice Variant of the Mouse SIRT3 Gene Encodes the Mitochondrial Precursor Protein
Cooper, H. M., Huang, J.-Y., Verdin, E. M., & Spelbrink, J. N. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004986 · Cited by 55
“The yeast ‘silent information regulator’ Sir2 is an NADdependant deacetylase with a role in regulating longevity in response to nutrient availability [1].”
BackgroundRole of Sirtuin 1 in metabolic regulation
Silva, J. P., & Wahlestedt, C. (2010) · Drug Discovery Today · doi:10.1016/j.drudis.2010.07.001 · Cited by 55
Li, N., Zhou, H., Ma, Z., Zhu, J., Liu, C., Song, P. K., Kong, C., Wu, H., Deng, W., & Tang, Q. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00854 · Cited by 55
“Sirtuin 1 deacetylase (SIRT1), the closest mammalian homolog of the yeast silent information regulator 2 protein, is a nicotinamide adenine dinucleotide NAD(+)-dependent deacetylase (Brachmann et al., 1995; Kaeberlein et al., 1999; Suzuki and Bartlett, 2014).”
BackgroundA Molecular Perspective on Sirtuin Activity
Teixeira, C. S. S., Cerqueira, N. M. F. S. A., Gomes, P., & Sousa, S. F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228609 · Cited by 57
“Efficient and correct deacetylation activity is of major importance for the correct functioning of several vital biological processes, including DNA recombination [71] and repair [72], transcriptional silencing [73], axonal protection [74], fat mobilization [75], apoptosis [76,77] and aging [78,79].”
BackgroundBioenergetics of aging and calorie restriction
Hunt, N. D., Hyun, D., Allard, J. S., Minor, R. K., Mattson, M. P., Ingram, D. K., & de Cabo, R. (2006) · Ageing Research Reviews · doi:10.1016/j.arr.2006.03.006 · Cited by 55
Armstrong, C. M., Kaeberlein, M. R., Imai, S., & Guarente, L. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.01-10-0482 · Cited by 55
“Deletions of SIR2 decrease yeast life span, whereas overexpressing SIR2 leads to an extension (Kaeberlein et al., 1999).”
BackgroundMethodInfluentialSelf-citationJiang, N., Du, G., Tobias, E., Wood, J. G., Whitaker, R., Neretti, N., & Helfand, S. L. (2013) · Aging · doi:10.18632/aging.100614 · Cited by 54
“mating type locus expression and sterility) [3, 18, 20].”
Growth factor, energy and nutrient sensing signalling pathways in metabolic ageing
Bettedi, L., & Foukas, L. C. (2017) · Biogerontology · doi:10.1007/s10522-017-9724-6 · Cited by 55
“Their implication in lifespan regulation emerged when increasing the dosage of the sirtuin Sir2 was found to extend replicative lifespan in yeast (Kaeberlein et al. 1999).”
BackgroundDeacetylation of metabolic enzymes by Sirt2 modulates pyruvate homeostasis to extend insect lifespan
Wang, T., Geng, S., Guan, Y.-M., & Xu, W. (2018) · Aging · doi:10.18632/aging.101447 · Cited by 54
“melanogaster as anti-aging proteins [19].”
BackgroundInfluentialGenome-wide analysis of functional sirtuin chromatin targets in yeast
Li, M., Valsakumar, V., Poorey, K., Bekiranov, S., & Smith, J. S. (2013) · Genome biology · doi:10.1186/gb-2013-14-5-r48 · Cited by 54
“Deletion of SIR2 shortens replicative life span, while increased SIR2 gene dosage extends both mean and maximum replicative life span [11].”
BackgroundInfluentialRecent aging research in Caenorhabditis elegans
Schaffitzel, E., & Hertweck, M. (2006) · Experimental Gerontology · doi:10.1016/j.exger.2006.02.008 · Cited by 58
Mitochondrial–nuclear epistasis: Implications for human aging and longevity
Tranah, G. J. (2010) · Ageing Research Reviews · doi:10.1016/j.arr.2010.06.003 · Cited by 55
Hot topics in aging research: protein translation, 2009
Kennedy, B. K., & Kaeberlein, M. R. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00522.x · Cited by 54
“Both enhanced Sir2 and Pnc1 function are known to result in lifespan extension (Kaeberlein et al., 1999; Anderson et al., 2003).”
BackgroundSelf-citationSaccharomyces cerevisiae SSD1-V Confers Longevity by a Sir2p-Independent Mechanism
Kaeberlein, M. R., Andalis, A. A., Liszt, G. B., Fink, G. R., & Guarente, L. (2004) · Genetics · doi:10.1534/genetics.166.4.1661 · Cited by 57
Self-citationThe Caenorhabditis elegans nicotinamidase PNC-1 enhances survival
van der Horst, A., Schavemaker, J. M., Berkel, W. P.-V., & Burgering, B. M. T. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2007.01.004 · Cited by 53
The role of protein arginine methylation in the formation of silent chromatinPreprint
Yu, M. C., Lamming, D. W., Eskin, J. A., Sinclair, D. A., & Silver, P. A. (2006) · Genes & Development · doi:10.1101/gad.1495206 · Cited by 57
“For example, the Sir1/2/3/4 complex functions to silence transcription at the mating-type loci, whereas a Sir2/3/4 complex mediates silencing at the telomeres (Kaeberlein et al. 1999).”
BackgroundSirtuins and the circadian clock interplay in cardioprotection: focus on sirtuin 1
Soni, S. K., Basu, P., Singaravel, M., Sharma, R., Pandi-Perumal, S. R., Cardinali, D. P., & Reiter, R. J. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03713-6 · Cited by 56
Chen, Y., Jiang, Y., Yang, Y., Huang, X., & Sun, C. (2021) · Neurotoxicity Research · doi:10.1007/s12640-021-00392-4 · Cited by 53
Resveratrol, sirtuins, and viruses
Yang, T., Li, S., Zhang, X., Pang, X., Lin, Q., & Cao, J. (2015) · Reviews in Medical Virology · doi:10.1002/rmv.1858 · Cited by 53
“The yeast Sir2 was found to mediate the effect of life span extension of caloric restriction [19].”
BackgroundDuarte, D. A., Rosales, M. A. B., Papadimitriou, A., Silva, K. C., Amancio, V. H. O., Mendonça, J. N., Lopes, N. P., de Faria, J. B. L., & de Faria, J. M. L. (2014) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2014.09.003 · Cited by 53
Loss of SIRT 4 decreases GLT ‐1‐dependent glutamate uptake and increases sensitivity to kainic acid
Shih, J., Liu, L., Mason, A., Higashimori, H., & Dönmez, G. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12942 · Cited by 54
“Physiologically, SIRTs were first discovered to increase lifespan by mediating the effects of calorie restriction (Kennedy et al. 1995; Kaeberlein et al. 1999).”
BackgroundMejía-Ramírez, E., Sánchez-Gorostiaga, A., Krimer, D. B., Schvartzman, J. B., & Hernández, P. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.19.8755-8761.2005 · Cited by 53
“In this budding yeast, Fob1p-dependent RFBs are also required for HOT1 recombination, the expansion and contraction of rRNA gene repeats, and the formation of extrachromosomal rRNA gene circles (11, 13, 14), indicating that fork arrest at RFBs promotes homologous recombination within the rRNA gene locus (4).”
BackgroundTrichostatin A Extends the Lifespan of Drosophila melanogaster by Elevating hsp22 Expression
Tao, D., Lü, J., Sun, H., Zhao, Y., Yuan, Z.-G., Li, X., & Huang, B. (2004) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/36.9.618 · Cited by 53
Insights into Lysine Deacetylation of Natively Folded Substrate Proteins by Sirtuins
Knyphausen, P., de Boor, S., Kuhlmann, N., Scislowski, L., Extra, A., Baldus, L., Schacherl, M., Baumann, U., Neundorf, I., & Lammers, M. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.726307 · Cited by 52
“Later, it was found that Sir2 regulates aging and life span in yeast and that it has KDAC activity (39, 40).”
BackgroundSIRT1‐SIRT3 Axis Regulates Cellular Response to Oxidative Stress and Etoposide
Carnevale, I., Pellegrini, L., D’Aquila, P., Saladini, S., Lococo, E., Polletta, L., Vernucci, E., Foglio, E., Coppola, S., Sansone, L., et al. (2016) · Journal of Cellular Physiology · doi:10.1002/jcp.25711 · Cited by 51
“The Silent Information Regulator 2 (SIR2) gene was shown to extend the life span of budding yeast by repressing genome instability (Sinclair and Guarente, 1997; Kaeberlein et al., 1999).”
BackgroundDoes eating less make you live longer and better? An update on calorie restriction
Picca, A., Pesce, V., & Lezza, A. M. S. (2017) · Clinical Interventions in Aging · doi:10.2147/cia.s126458 · Cited by 57
“The role of sirtuins pathway in regulating lifespan was discovered in yeast, 101 but the family of these NAD + -dependent protein deacetylases is present in all organisms where inter-venes favoring longevity 102 and, by removing acetyl residues, it regulates the activity of many enzymes.”
Easlon, E. J., Tsang, F. A., Dilova, I., Wang, C., Lu, S.-P., Skinner, C., & Lin, S.-J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m607661200 · Cited by 55
The sirtuin class of histone deacetylases: Regulation and roles in lipid metabolism
Fiorino, E., Giudici, M., Ferrari, A., Mitro, N., Caruso, D., Fabiani, E. D., & Crestani, M. (2014) · IUBMB Life · doi:10.1002/iub.1246 · Cited by 54
“Since the discovery of Sir2 involvement in increasing yeast longevity (8) and that calorie restriction activates Sir2 leading to lifespan extension (9), a growing number of studies on sirtuins have been published, revealing their important role in calorie restriction, agingrelated diseases and metabolic homeostasis (1…”
BackgrounddSir2 and longevity in Drosophila
Frankel, S. A., Ziafazeli, T., & Rogina, B. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.08.007 · Cited by 53
“The role of Sir2 in yeast longevity was discovered when it was found that having an extra copy of the sir2 gene extended replicative life span while sir2 mutants have a shorter life span (Kaeberlein et al., 1999).”
A global requirement for the HIR complex in the assembly of chromatin
Amin, A. D., Vishnoi, N., & Prochasson, P. (2011) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2011.07.008 · Cited by 52
Inactivation of the Sas2 histone acetyltransferase delays senescence driven by telomere dysfunction
Kozak, M., Chavez, A., Dang, W., Berger, S. L., Ashok, A., Guo, X., & Johnson, F. B. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.314 · Cited by 52
“This regulation ranges from lifespan inhibition to extension, for example limiting lifespan during the chronological ageing of yeast, but extending the replicative lifespan of yeast mother cells (Kaeberlein et al, 1999; Fabrizio et al, 2005).”
BackgroundKaeberlein, M. R. (2015) · Veterinary Pathology · doi:10.1177/0300985815591082 · Cited by 56
“Sirtuins first became implicated in aging based on studies in budding yeast demonstrating that overexpression of the yeast Sir2 gene was sufficient to extend lifespan.(43) Mammals have seven sirtuin genes, SIRT1–SIRT7.”
BackgroundSelf-citationLi, L., Lu, Y. C., Qin, L., Bar‐Joseph, Z., Werner‐Washburne, M., & Breeden, L. L. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e09-04-0347 · Cited by 51
“The SIR2 (Kaeberlein et al., 1999), MPT5 (Kennedy et al., 1997) and LAG1 (Jiang et al., 2004) gene products promote longevity, and their mRNA levels are higher in SSD1-V cells.”
BackgroundSIRT1 Polymorphism, Long-Term Survival and Glucose Tolerance in the General Population
Figarska, S. M., Vonk, J. M., & Boezen, H. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058636 · Cited by 49
“Initially, overexpression of the silent information regulator Sir2, nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase, has shown a beneficial effect on lifespan in budding yeast (Saccharomyces cerevisae) [2].”
BackgroundSIRT6 Is Required for Normal Retinal Function
Silberman, D. M., Ross, K. N., Sande, P. H., Kubota, S., Ramaswamy, S., Apte, R. S., & Mostoslavsky, R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0098831 · Cited by 52
“Sirtuins are an evolutionarily conserved family of NADdependent deacylases that have been involved in many cellular responses to stress, including chromatin modifications, genomic stability, metabolism, inflammation, cellular senescence and organismal lifespan [16,17,18].”
BackgroundKobayashi, T., & Sasaki, M. (2017) · FEMS Yeast Research · doi:10.1093/femsyr/fox001 · Cited by 54
Sirtuins Expression and Their Role in Retinal Diseases
Balaiya, S., Abu‐Amero, K. K., Kondkar, A. A., & Chalam, K. V. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/3187594 · Cited by 52
NAD+ Deficits in Age-Related Diseases and Cancer
Garrido, A., & Djouder, N. (2017) · Trends in cancer · doi:10.1016/j.trecan.2017.06.001 · Cited by 53
Targeting Sirtuins: Substrate Specificity and Inhibitor Design
Rajabi, N., Galleano, I., Madsen, A. S., & Olsen, C. A. (2018) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2017.11.003 · Cited by 52
Sirtuins, nuclear hormone receptor acetylation and transcriptional regulation
Whittle, J. R., Powell, M. J., Popov, V. M., Shirley, L. A., Wang, C., & Pestell, R. G. (2007) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2007.07.007 · Cited by 51
SIRT1 in metabolic syndrome: Where to target matters
Wang, Y., Xu, C., Liang, Y., & Vanhoutte, P. M. (2012) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.08.009 · Cited by 51
Advances in mouse models of prostate cancer
Ahmad, I., Sansom, O. J., & Leung, H. Y. (2008) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399408000689 · Cited by 50
The place of genetics in ageing research
Barzilai, N., Guarente, L., Kirkwood, T. B. L., Partridge, L., Rando, T. A., & Slagboom, P. E. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3290 · Cited by 53
Self-citationQuantitation of NAD+ biosynthesis from the salvage pathway in Saccharomyces cerevisiae
Sporty, J. L., Lin, S.-J., Kato, M., Ognibene, T. J., Stewart, B. J., Turteltaub, K. W., & Bench, G. (2009) · Yeast · doi:10.1002/yea.1671 · Cited by 51
“Studies of ageing in S. cerevisiae have also led to the finding that the SIR2 gene regulates the lifespan in yeast mother cells (Kaeberlein et al., 1999).”
BackgroundHuberts, D. H. E. W., González, J., Lee, S. S., Litsios, A., Hubmann, G., Wit, E. C., & Heinemann, M. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1410024111 · Cited by 60
Epigenetic regulation in heart failure
Kim, S. Y., Morales, C. R., Gillette, T. G., & Hill, J. A. (2016) · Current Opinion in Cardiology · doi:10.1097/hco.0000000000000276 · Cited by 49
Molina‐Serrano, D., Schiza, V., Demosthenous, C., Stavrou, E., Oppelt, J., Kyriakou, D., Liu, W., Zisser, G., Bergler, H., Dang, W., et al. (2016) · EMBO Reports · doi:10.15252/embr.201642540 · Cited by 48
Dosis Facit Sanitatem—Concentration-Dependent Effects of Resveratrol on Mitochondria
Madreiter‐Sokolowski, C. T., Sokolowski, A., & Graier, W. F. (2017) · Nutrients · doi:10.3390/nu9101117 · Cited by 52
“This deacetylase has been shown to enhance mitochondrial biogenesis [114] and metabolism [115] as well as to extend lifespan in yeast [116], worms [117] and flies [118].”
BackgroundSasaki, Y., Ikeda, Y., Uchikado, Y., Akasaki, Y., Sadoshima, J., & Ohishi, M. (2021) · Journal of the American Heart Association · doi:10.1161/jaha.120.019310 · Cited by 52
Sirtuins of parasitic protozoa: In search of function(s)
Religa, A. A., & Waters, A. P. (2012) · Molecular and Biochemical Parasitology · doi:10.1016/j.molbiopara.2012.08.003 · Cited by 51
The eye as a model of ageing in translational research – Molecular, epigenetic and clinical aspects
Pathai, S., Shiels, P. G., Lawn, S. D., Cook, C., & Gilbert, C. E. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2012.11.002 · Cited by 50
The NAD + -Dependent Family of Sirtuins in Cerebral Ischemia and Preconditioning
Khoury, N., Koronowski, K. B., Young, J. I., & Pérez‐Pinzón, M. A. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7258 · Cited by 51
“Cells carrying a mutant form of Sir2 had a significantly reduced lifespan compared to wild types, whereas strains overexpressing Sir2 exhibited a noticeably increased lifespan (71).”
BackgroundThe Role of Ghrelin and Ghrelin Signaling in Aging
Amitani, M. S., Amitani, H., Cheng, K., Kairupan, T. S., Sameshima, N., Shimoshikiryo, I., Mizuma, K., Rokot, N. T., Nerome, Y., Owaki, T., et al. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18071511 · Cited by 53
“In experimental models, a variant with inactivated Sir2 is short-lived, and a variant that overexpresses Sir2 has a longer life span than the wild type [34].”
BackgroundBrain aging: A Ianus‐faced player between health and neurodegeneration
Vanni, S., Baldeschi, A. C., Zattoni, M., & Legname, G. (2019) · Journal of Neuroscience Research · doi:10.1002/jnr.24379 · Cited by 54
A fln-2 mutation affects lethal pathology and lifespan in C. elegans
Zhao, Y., Wang, H., Poole, R. J., & Gems, D. (2019) · Nature Communications · doi:10.1038/s41467-019-13062-z · Cited by 48
Zhou, D., Ran, Y., Yu, R., Liu, Z., Ran, D., & Liu, Z. (2023) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2023.110632 · Cited by 53
The sirtuins: Markers of metabolic health
Covington, J. D., & Bajpeyi, S. (2015) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201500340 · Cited by 51
Quantitative evidence for early life fitness defects from 32 longevity-associated alleles in yeast
Delaney, J. R., Murakami, C. J., Olsen, B., Kennedy, B. K., & Kaeberlein, M. R. (2011) · Cell Cycle · doi:10.4161/cc.10.1.14457 · Cited by 52
Self-citationA mathematical model of ageing in yeast
Gillespie, C. S., Proctor, C. J., Boys, R. J., Shanley, D. P., Wilkinson, D. J., & Kirkwood, T. B. L. (2004) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2004.03.015 · Cited by 49
Sirtuin regulation in calorie restriction
Qiu, X., Brown, K. V., Moran, Y., & Chen, D. (2009) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2009.09.015 · Cited by 50
Transcription factor NFκB regulates the expression of the histone deacetylase SIRT1
Katto, J., Engel, N., Abbas, W., Herbein, G., & Mahlknecht, U. (2013) · Clinical Epigenetics · doi:10.1186/1868-7083-5-11 · Cited by 49
“It also suppresses the recombination of rDNA and thereby lowers the formation of toxic extrachromosomal rDNA rings, which extends lifespan in yeast cells dramatically [5].”
BackgroundDerous, D., Mitchell, S. E., Wang, L., Green, C. L., Wang, Y., Chen, L., Han, J. J., Promislow, D., Lusseau, D., Douglas, A., et al. (2017) · Aging · doi:10.18632/aging.101269 · Cited by 49
Ribosomal DNA and the nucleolus at the heart of aging
Kasselimi, E., Pefani, D., Taraviras, S. L., & Lygerou, Z. (2022) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2021.12.007 · Cited by 53
Energy, quiescence and the cellular basis of animal life spans
Stuart, J. A., & Brown, M. F. (2005) · Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · doi:10.1016/j.cbpa.2005.11.002 · Cited by 52
SIR2 and aging – the exception that proves the rule
Guarente, L. (2001) · Trends in Genetics · doi:10.1016/s0168-9525(01)02339-3 · Cited by 49
Self-citationTargeting PGC-1α to control energy homeostasis
Wu, Z., & Boss, O. (2007) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.11.10.1329 · Cited by 50
“In yeast and flies, Sir2 is an NAD + -dependent histone deacetylase that, when overexpressed, extends the lifespan of the organism [85,86] .”
BackgroundExpression of SIRT1 and SIRT3 varies according to age in mice
Kwon, Y.-H., Kim, J., Lee, C.-Y., & Kim, H. (2015) · Anatomy & Cell Biology · doi:10.5115/acb.2015.48.1.54 · Cited by 48
“First described as a silencing factor in yeast (silencing information regulator, SIR), Sirt2 has been recognized as a modulator of the yeast life span [2].”
BackgroundPerico, N., Remuzzi, G., & Benigni, A. (2011) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0b013e328344c327 · Cited by 48
Sirtuin 5 is Anti-apoptotic and Anti-oxidative in Cultured SH-EP Neuroblastoma Cells
Liang, F., Wang, X., Ow, S.-H., Chen, W., & Ong, W. C. (2016) · Neurotoxicity Research · doi:10.1007/s12640-016-9664-y · Cited by 49
Genetic architecture of natural variation in visual senescence in Drosophila
Carbone, M. A., Ah, Y., Huang, W., Lyman, R. A., Meadors, T. B., Yamamoto, R., Anholt, R. R. H., & Mackay, T. F. C. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1613833113 · Cited by 48
“Genes involved in insulin signaling and oxidative stress have been implicated as evolutionarily conserved mechanisms affecting life span in Mus musculus (53, 54), Drosophila (55–57), Caenorhabditis elegans (58, 59), and yeast (60, 61).”
BackgroundMoreno, C. L., & Mobbs, C. V. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.11.013 · Cited by 50
Research progress on sirtuins family members and cell senescence
Wang, T., Wang, Y., Liu, L., Jiang, Z., Li, X., Tong, R., He, J., & Shi, J. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112207 · Cited by 48
Fu, W., Li, H., Fu, H., Zhao, S., Shi, W., Sun, M., & Li, Y. (2020) · Journal of Immunology Research · doi:10.1155/2020/8820355 · Cited by 49
Hisahara, S., Chiba, S., Matsumoto, H., & Horio, Y. (2005) · Journal of Pharmacological Sciences · doi:10.1254/jphs.fmj05001x2 · Cited by 48
Wang, W., Li, Y., Zhang, Y., Ye, T., Wang, K., Li, S., & Zhang, Y. (2023) · Cardiovascular Diabetology · doi:10.1186/s12933-023-02040-x · Cited by 50
“SIRT1 is a class III histone deacetylase that relies on nicotinamide adenine dinucleotide as a cofactor [11–13].”
BackgroundR-loops highlight the nucleus in ALS
Salvi, J. S., & Mekhail, K. (2015) · Nucleus · doi:10.1080/19491034.2015.1004952 · Cited by 48
Targeting sirtuins for the treatment of diabetes
Huynh, F. K., Hershberger, K. A., & Hirschey, M. D. (2013) · Diabetes Management · doi:10.2217/dmt.13.6 · Cited by 48
Gis1 and Rph1 Regulate Glycerol and Acetate Metabolism in Glucose Depleted Yeast Cells
Westholm, J. O., Tronnersjö, S., Nordberg, N., Olsson, I., Komorowski, J., & Ronne, H. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031577 · Cited by 46
“Replicative aging has been linked to the accumulation of extrachromosomal rDNA circles (ERCs) in yeast [43].”
BackgroundSirtuins, Bioageing, and Cancer
McGuinness, D. H., McGuinness, D. H., McCaul, J. A., & Shiels, P. G. (2011) · Journal of Aging Research · doi:10.4061/2011/235754 · Cited by 48
“Typically, Sirtuins have been implicated in the preservation of genomic stability and in the prolongation of lifespan though many of their target interactions remain unknown.”
BackgroundThe Sgs1 Helicase of Saccharomyces cerevisiae Inhibits Retrotransposition of Ty1 Multimeric Arrays
Bryk, M., Banerjee, M., Conte, D., & Curcio, M. J. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.16.5374-5388.2001 · Cited by 46
“Furthermore, both SIR2 and ZDS2 forestall aging (31, 52).”
BackgroundMitochondrial sirtuins in the heart
Bugger, H., Witt, C. N., & Bode, C. (2016) · Heart Failure Reviews · doi:10.1007/s10741-016-9570-7 · Cited by 47
The role of autophagy in the regulation of yeast life span
Tyler, J. K., & Johnson, J. E. (2018) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13549 · Cited by 49
Dabke, P., & Das, A. M. (2020) · Nutrients · doi:10.3390/nu12082379 · Cited by 47
“Sirtuins: The term “Sirtuin” is derived from Sir2 protein (belonging to the silent information regulator family), a group of proteins described in Saccharomyces cerevisiae (yeast), particularly pertaining to its function in longevity [18].”
BackgroundHistone deacetylase 2: A potential therapeutic target for cancer and neurodegenerative disorders
Gediya, P., Parikh, P. K., Vyas, V. K., & Ghate, M. D. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113332 · Cited by 48
Histone deficiency and accelerated replication stress in T cell aging
Kim, C., Jin, J., Ye, Z., Jadhav, R. R., Gustafson, C. E., Hu, B., Cao, W., Tian, L., Weyand, C. M., & Goronzy, J. J. (2021) · Journal of Clinical Investigation · doi:10.1172/jci143632 · Cited by 44
“In yeast and worms, Sir2, the nonmammalian homolog of SIRT1, promotes organismal life span extension (46, 47).”
BackgroundProspective Pharmacological Potential of Resveratrol in Delaying Kidney Aging
Uddin, M. J., Farjana, M., Moni, A., Hossain, K. S., Hannan, M. A., & Ha, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22158258 · Cited by 49
“SIRT2 overexpression may extend longevity in the yeast Saccharomyces cerevisiae by 30%, while suppression of the SIRT2 gene causes a reduction of its lifespan by almost half [160].”
BackgroundrDNA array length is a major determinant of replicative lifespan in budding yeast
Hotz, M., Thayer, N. H., Hendrickson, D. G., Schinski, E. L., Xu, J., & Gottschling, D. E. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2119593119 · Cited by 46
“However, having an abundance of ERCs in young cells becomes a burden later in life.”
BackgroundInfluentialThe Enigmatic Role of Sir2 in Aging
Kennedy, B. K. (2005) · Cell · doi:10.1016/j.cell.2005.11.002 · Cited by 49
Regulation of Gene Expression through Food—Curcumin as a Sirtuin Activity Modulator
Ungurianu, A., Zanfirescu, A., & Margina, D. M. (2022) · Plants · doi:10.3390/plants11131741 · Cited by 50
Yao, Y., Tsuchiyama, S. K., Yang, C., Bulteau, A., He, C. Z., Robison, B., Tsuchiya, M., Miller, D. M., Briones, V., Tar, K., et al. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1004968 · Cited by 46
“Overexpression of SIR2 confers increased longevity [56].”
BackgroundKahyo, T., Ichikawa, S., Hatanaka, T., Yamada, M. K., & Setou, M. (2008) · Journal of Pharmacological Sciences · doi:10.1254/jphs.08203fp · Cited by 47
Exploring the power of yeast to model aging and age-related neurodegenerative disorders
Oliveira, A. V., Vilaça, R., dos Santos, C. N., Costa, V., & Menezes, R. (2016) · Biogerontology · doi:10.1007/s10522-016-9666-4 · Cited by 50
“Consistently, the levels of Sir2 decrease during aging with a concomitant increase of ERCs (Dang et al. 2009) and sir2D mutants exhibit a shortened RLS (Kaeberlein et al. 1999).”
BackgroundMarti, N., Bouchoucha, N., Sauter, K., & Flück, C. E. (2017) · PLoS ONE · doi:10.1371/journal.pone.0174224 · Cited by 46
Candida albicans, a distinctive fungal model for cellular aging study
Fu, X., Meng, F., Hu, Y., & Zhou, J. (2008) · Aging Cell · doi:10.1111/j.1474-9726.2008.00424.x · Cited by 49
“Therefore, it is suggested that ERCs are a cause of yeast aging (Sinclair & Guarente, 1997), and Sir2 plays a specific role in promoting longevity.”
InfluentialCalorie restriction reduces rDNA recombination independently of rDNA silencing
Riesen, M., & Morgan, A. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00514.x · Cited by 46
“While this remains a plausible mechanism, it is interesting to note that in fob1 ⁄ sir2 double mutants, which have extremely low ERC levels, CR increases lifespan and reduces rDNA recombination (Kaeberlein et al., 1999, 2004; Lamming et al., 2005).”
BackgroundPathogen evolution in a vaccinated world
Read, A. F., & Mackinnon, M. J. (2007) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780199207466.003.0011 · Cited by 45
Metadata
- Authors
- Kaeberlein, M., McVey, M., & Guarente, L.
- Affiliations
- Massachusetts Institute of Technology (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1999-10-01
- Volume
- 13
- Issue
- 19
- Pages
- 2570-2580
- ISSN
- 0890-9369 (ISSN-L)
- PMC
- PMC317077
- OpenAlex
- W2157649587
- Cited by
- 2,253
- References
- 52
- Citations by year
- 2026: 27 · 2025: 64 · 2024: 50 · 2023: 80 · 2022: 76 · 2021: 91 · 2020: 93 · 2019: 101 · 2018: 126 · 2017: 73 · 2016: 123 · 2015: 104 · 2014: 111 · 2013: 127 · 2012: 123
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (T32GM07287, T32GM007287)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- Sir2p, Sir3p, longevity, lifespan regulation, Saccharomyces cerevisiae, non-homologous end joining, replication block, gene dosage, aging
- MeSH terms
- Mating Factor, DNA-Binding Proteins, DNA, Fungal, DNA, Ribosomal, Fungal Proteins, Histone Deacetylases, Peptides, Phenotype, Saccharomyces cerevisiae, Trans-Activators, Mutagenesis, Saccharomyces cerevisiae Proteins, 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
