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
Flagged first, then by citations
1 of the 52 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 401–500 of 1,004
Shankar, S., & Srivastava, R. K. (2007) · Advances in experimental medicine and biology · doi:10.1007/978-1-4020-6554-5_13 · Cited by 160
Chu, F., Chou, P. M., Zheng, X. S., Mirkin, B. L., & Rebbaa, A. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-2002 · Cited by 162
Easlon, E. J., Tsang, F. A., Skinner, C., Wang, C., & Lin, S.-J. (2008) · Genes & Development · doi:10.1101/gad.1648308 · Cited by 161
“The pRS305-Sir2 plasmid carrying a single copy of the SIR2 gene and the promoter region has been described previously (Kaeberlein et al. 1999).”
BackgroundMethodInfluentialNovel Role of the SIRT1 in Endocrine and Metabolic Diseases
Lu, C., Zhao, H., Liu, Y., Yang, Z., Yao, H., Liu, T., Gou, T., Wang, L., Zhang, J., Tian, Y., et al. (2023) · International Journal of Biological Sciences · doi:10.7150/ijbs.78654 · Cited by 160
“Increasing the dosage or activity of Sir2 has been shown to extend the life spans of yeast, worms, and flies, while deletions or mutations of the Sir2 reverses the result [21, 23, 24].”
Li, Z., & Zhu, W. (2014) · International Journal of Biological Sciences · doi:10.7150/ijbs.9067 · Cited by 164
“cerevisiae [133].”
Mechanisms of Lifespan Regulation by Calorie Restriction and Intermittent Fasting in Model Organisms
Hwangbo, D., Lee, H., Abozaid, L. S., & Min, K. (2020) · Nutrients · doi:10.3390/nu12041194 · Cited by 173
Enzymatic activities of Sir2 and chromatin silencing
Moazed, D. (2001) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00202-7 · Cited by 160
The role of insulin and IGF-1 signaling in longevity
Katić, M., & Kahn, C. R. (2005) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-004-4297-y · Cited by 163
Resveratrol and life extension
Agarwal, B., & Baur, J. A. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05850.x · Cited by 163
Ruminations on dietary restriction and aging
Kennedy, B. K., Steffen, K. K., & Kaeberlein, M. R. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-6470-y · Cited by 161
Self-citationZhang, G., Deng, Y.-J., Xie, Q.-Q., Ren, E., Ma, Z., He, X., Gao, Y., & Kang, X. (2020) · Clinica Chimica Acta · doi:10.1016/j.cca.2020.04.016 · Cited by 158
Calorie restriction and SIR2 genes—Towards a mechanism
Guarente, L. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2005.03.013 · Cited by 160
Self-citationShen, P., Yue, Y., Zheng, J., & Park, Y. (2017) · Annual Review of Food Science and Technology · doi:10.1146/annurev-food-030117-012709 · Cited by 161
Inhibition of mammalian S6 kinase by resveratrol suppresses autophagy
Armour, S. M., Baur, J. A., Hsieh, S. N., Land-Bracha, A., Thomas, S. Μ., & Sinclair, D. A. (2009) · Aging · doi:10.18632/aging.100056 · Cited by 160
“Resveratrol has been characterized as an activator of SIRT1/Sir2, which are members of a family of enzymes that promote longevity in lower organisms [7, 8, 31-33].”
BackgroundThe controversial world of sirtuins
Dang, W. (2012) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2012.08.003 · Cited by 158
Goto, M. (2008) · PubMed · Cited by 154
Borra, M. T., O'Neill, F. J., Jackson, M. D., Marshall, B. L., Verdin, E. M., Foltz, K. R., & Denu, J. M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111830200 · Cited by 155
Morrow, G., Battistini, S., Zhang, P., & Tanguay, R. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.c400357200 · Cited by 157
Huang, J., Brito, I., Villén, J., Gygi, S. P., Amon, A., & Moazed, D. (2006) · Genes & Development · doi:10.1101/gad.1472706 · Cited by 159
“Unequal sister chromatid exchange assays Assays were performed as previously described (Kaeberlein et al. 1999).”
MethodDietary and Metabolic Control of Stem Cell Function in Physiology and Cancer
Mihaylova, M. M., Sabatini, D. M., & Yilmaz, Ö. H. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.02.008 · Cited by 158
“SIRT1 bears the greatest sequence homology to the yeast Sir2, which as been shown to increase yeast lifespan (Kaeberlein et al., 1999), and is the best-studied mammalian member in the context of stem cell biology and aging (reviewed in Rafalski et al.”
Diverse and dynamic functions of the Sir silencing complex
Guarente, L. (1999) · Nature Genetics · doi:10.1038/15458 · Cited by 154
Self-citationAcetylation of Yeast AMPK Controls Intrinsic Aging Independently of Caloric Restriction
Lu, J., Lin, Y.-Y., Sheu, J., Wu, J., Lee, F.-J. S., Chen, Y., Lin, M.-I., Chiang, F., Tai, T. Y., Berger, S. L., et al. (2011) · Cell · doi:10.1016/j.cell.2011.07.044 · Cited by 158
“Replicative Life Span Determination and Statistical Analysis Replicative life span was carried out as described (Kaeberlein et al., 1999).”
MethodLaemmle, A., Lechleiter, A., Roh, V., Schwarz, C., Portmann, S., Furer, C., Keogh, A., Tschan, M. P., Candinas, D., Vorburger, S. A., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033433 · Cited by 156
“drosophila and mammals [13,14,15,16].”
The Effect of Replication Initiation on Gene Amplification in the rDNA and Its Relationship to Aging
Ganley, A. R. D., Ide, S., Saka, K., & Kobayashi, T. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.07.012 · Cited by 152
Liu, G., Park, S., Imbesi, M., Nathan, W. J., Zou, X., Zhu, Y., Jiang, H., Parisiadou, L., & Gius, D. R. (2016) · Antioxidants and Redox Signaling · doi:10.1089/ars.2016.6662 · Cited by 158
“S irtuins have received significant attention since the discovery that the yeast sirtuin (silent information regulator 2 or Sir2) gene extends yeast lifespan (28).”
BackgroundStructural Basis for the Mechanism and Regulation of Sir2 Enzymes
Avalos, J. L., Boeke, J. D., & Wolberger, C. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00082-6 · Cited by 153
Transcriptional silencing at Saccharomyces telomeres: implications for other organisms
Tham, W., & Zakian, V. A. (2002) · Oncogene · doi:10.1038/sj.onc.1205078 · Cited by 150
“This re-localization is thought to protect ribosomal DNA from breakage and recombination (Gottlieb and Esposito, 1989; Kaeberlein et al., 1999).”
BackgroundSir2: An NAD-dependent Histone Deacetylase That Connects Chromatin Silencing, Metabolism, and AgingPreprint
Mai, S., Johnson, F. B., MARCINIAK, R. A., MCVEY, M., Park, P. U., & Guarente, L. (2000) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2000.65.297 · Cited by 155
Self-citationZhu, C.-T., Ingelmo, P., & Rand, D. M. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004354 · Cited by 153
“The up-regulation of SIR2 leads to lifespan extension in many model organisms [15,18,40,47,48,49] and there are sound reasons why this process may involve a mito-SIR2 interaction.”
BackgroundMitoenergetic failure in Alzheimer disease
Parihar, M. S., & Brewer, G. J. (2006) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00232.2006 · Cited by 153
Sirtuin 1 (SIRT1): The Misunderstood HDAC
Stünkel, W., & Campbell, R. M. (2011) · SLAS DISCOVERY · doi:10.1177/1087057111422103 · Cited by 154
Testa, G., Biasi, F., Poli, G., & Chiarpotto, E. (2014) · Current Pharmaceutical Design · doi:10.2174/13816128113196660699 · Cited by 153
“In particular, overexpression of Sir2, orthologue of the mammalian SIRT-1, has been demonstrated to increase the yeast lifespan [170], and that of Caenorhabditis elegans [171] and Drosophila [172], and Sir2 has been shown to be essential in the mechanism of lifespan extension by CR in the same species [173-175].”
BackgroundResveratrol protects against peripheral deficits in a mouse model of Huntington's disease
Ho, D. J., Calingasan, N. Y., Wille, E. J., Dumont, M., & Beal, M. F. (2010) · Experimental Neurology · doi:10.1016/j.expneurol.2010.05.006 · Cited by 148
Coenzyme Specificity of Sir2 Protein Deacetylases
Schmidt, M. T., Smith, B. C., Jackson, M. D., & Denu, J. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407484200 · Cited by 150
SIRT6 in DNA repair, metabolism and ageing
Lombard, D. B., Schwer, B., Alt, F. W., & Mostoslavsky, R. (2008) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2007.01902.x · Cited by 148
Longo, V. D., & Fabrizio, P. (2002) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-002-8477-8 · Cited by 147
Fan, H. X., Yang, H., Li, Y., Wang, Y., He, W., & Hao, C. (2013) · Kidney International · doi:10.1038/ki.2012.394 · Cited by 147
Biological and Potential Therapeutic Roles of Sirtuin Deacetylases
Taylor, D. M., Maxwell, M. M., Luthi‐Carter, R., & Kazantsev, A. G. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-8357-y · Cited by 146
Biochemical effects of SIRT1 activators
Baur, J. A. (2009) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2009.10.025 · Cited by 150
“Loss of Sir2 dramatically accelerates ERC formation and shortens lifespan, while increasing Sir2 activity reduces ERCs and extends yeast lifespan [3].”
BackgroundChemical Activation of Sir2-Dependent Silencing by Relief of Nicotinamide Inhibition
Sauve, A. A., Moir, R. D., Schramm, V. L., & Willis, I. M. (2005) · Molecular Cell · doi:10.1016/j.molcel.2004.12.032 · Cited by 144
Kaeberlein, M. R., Andalis, A. A., Fink, G. R., & Guarente, L. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.22.8056-8066.2002 · Cited by 143
“In this experiment, HMLa was deleted from sir2 strains to prevent a and coexpression, which has been demonstrated to shorten life span in haploid cells (21).”
BackgroundMethodSelf-citationYu, H., Ye, W., Wu, J., Meng, X., Liu, R., Ying, X., Zhou, Y., Wang, H., Pan, C., & Huang, W. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-2952 · Cited by 143
“Sirtuins are homologous with yeast sirtuin silent information regulator 2 (Sir2), which was originally described as a transcriptional silencing regulator of mating-type loci, telomeres, and ribosomal DNA (4, 5) and extends the yeast lifespan (6).”
BackgroundThe Diversity of Histone Versus Nonhistone Sirtuin Substrates
Martínez‐Redondo, P., & Vaquero, A. (2013) · Genes & Cancer · doi:10.1177/1947601913483767 · Cited by 145
The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae
Gartenberg, M. R., & Smith, J. S. (2016) · Genetics · doi:10.1534/genetics.112.145243 · Cited by 148
“Sir2, on the other hand, lengthens RLS by suppressing rDNA recombination and thus, reducing the production of ERCs (Figure 13B) (Kaeberlein et al. 1999).”
BackgroundGenome Organization in and around the Nucleolus
Bersaglieri, C., & Santoro, R. (2019) · Cells · doi:10.3390/cells8060579 · Cited by 151
“Finally, in Saccharomyces cerevisiae, mutations in SIR2, a factor regulating silencing, induce an increase in homologous recombination at the rRNA gene locus, which results in the formation of extrachromosomal rDNA circles in the nucleolus that have an impact in cell senescence and aging [96,97].”
BackgroundNAD – new roles in signalling and gene regulation in plants
Hunt, L., Lerner, F., & Ziegler, M. (2004) · New Phytologist · doi:10.1111/j.1469-8137.2004.01087.x · Cited by 139
“, 1993), and an additional copy of the Sir2 gene increases yeast lifespan by 30% (Kaeberlein et al., 1999).”
BackgroundThe Information Theory of Aging
Lu, Y. R., Tian, X., & Sinclair, D. A. (2023) · Nature Aging · doi:10.1038/s43587-023-00527-6 · Cited by 141
“Similar to yeast, mammalian Sir2 homologs, SIRT1, SIRT6 and SIRT7, move to sites of DNA damage to assist with DSB repair, causing the ectopic transcription of hundreds of genes, satellite repeat RNA and transposons that can increase inflammation 6,29,31 (Fig.”
Regulation of Sirtuin Function by Posttranslational Modifications
Flick, F., & Lüscher, B. (2012) · Frontiers in Pharmacology · doi:10.3389/fphar.2012.00029 · Cited by 144
“Indeed overexpression of Sir2 was shown to increase lifespan in yeast (Kaeberlein et al., 1999).”
BackgroundSIRT1 modulates MAPK pathways in ischemic–reperfused cardiomyocytes
Becatti, M., Taddei, N., Cecchi, C., Nassi, N., Nassi, P., & Fiorillo, C. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-0925-5 · Cited by 141
Epigenetic Regulation of miR-34a Expression in Alcoholic Liver Injury
Meng, F., Glaser, S. S., Francis, H., Yang, F., Han, Y., Stokes, A., Staloch, D. A., McCarra, J., Liu, J., Venter, J. K., et al. (2012) · American Journal Of Pathology · doi:10.1016/j.ajpath.2012.06.010 · Cited by 143
Zhang, H., Zhao, Y. J., & Zhou, D. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx825 · Cited by 142
Metabolic Signaling to ChromatinPreprint
Berger, S. L., & Sassone‐Corsi, P. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a019463 · Cited by 145
Essential Role of SIRT1 Signaling in the Nucleus Accumbens in Cocaine and Morphine Action
Ferguson, D., Koo, J. W., Feng, J., Heller, E. A., Rabkin, J., Heshmati, M., Renthal, W. R., Neve, R. L., Liu, X., Shao, N., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.1284-13.2013 · Cited by 139
“The most studied sirtuin is SIRT1, which through regulating the acetylation state of several histone and nonhistone proteins is implicated in diverse aspects of cellular physiology (Kaeberlein et al., 1999; Bellet and Sassone-Corsi, 2010; Sassone-Corsi, 2012).”
BackgroundAgeing in the musculoskeletal system
Roberts, S., Colombier, P., Sowman, A., Mennan, C., Rölfing, J. D., Guicheux, J., & Edwards, J. (2016) · Acta Orthopaedica · doi:10.1080/17453674.2016.1244750 · Cited by 149
“The sirtuin gene family is closely linked to the regulation of lifespan (Kaeberlein et al. 1999).”
BackgroundInfluentialSIRT2 as a Therapeutic Target for Age-Related Disorders
de Oliveira, R. M., Sarkander, J., Kazantsev, A. G., & Outeiro, T. F. (2012) · Frontiers in Pharmacology · doi:10.3389/fphar.2012.00082 · Cited by 141
“Original studies of aging in S. cerevisiae led to the discovery that extra copies of the SIR2 gene extended lifespan by 50%, whereas SIR2 deletion reduced longevity (Kaeberlein et al., 1999).”
BackgroundNF-κB Signaling in the Aging Process
Salminen, A., & Kaarniranta, K. (2009) · Journal of Clinical Immunology · doi:10.1007/s10875-009-9296-6 · Cited by 140
“Later studies elucidated that the promotion of yeast longevity was induced by Sir2 (silent information regulator 2) [50].”
BackgroundAlcaín, F. J., & Villalba, J. M. (2009) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543770902762893 · Cited by 137
“All the evidence suggests that the molecular mechanisms of CR are mediated by sirtuins in yeast, worms, flies, and mammals [31-34]; CR has induced sirtuin activity in all the species studied.”
BackgroundSirtuin and metabolic kidney disease
Wakino, S., Hasegawa, K., & Itoh, H. (2015) · Kidney International · doi:10.1038/ki.2015.157 · Cited by 136
SirT1-null mice develop tumors at normal rates but are poorly protected by resveratrol
Boily, G., He, X. H., Pearce, B., Jardine, K. E., & McBurney, M. W. (2009) · Oncogene · doi:10.1038/onc.2009.147 · Cited by 137
Chronic Inflammation in the Context of Everyday Life: Dietary Changes as Mitigating Factors
Margina, D. M., Ungurianu, A., Purdel, C. N., Tsoukalas, D., Sarandi, E., Thanasoula, M., Tekos, F., Mesnage, R., Kouretas, D., & Tsatsakis, A. M. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17114135 · Cited by 146
“SIRT1 is modulated by NAD+ level and is increased in energy depletion states (such as fasting or exercise) for which NAD+ is a sensor, which contributes to the reduction of inflammation through NF-Kβ down-regulation and related transcription factors [132,182,183].”
BackgroundNAD metabolism: Role in senescence regulation and aging
Chini, C. C. S., Cordeiro, H. S., Tran, N. L. K., & Chini, E. N. (2023) · Aging Cell · doi:10.1111/acel.13920 · Cited by 148
“SIRT3 was among the first genes identified to extend lifespan (Benigni et al., 2019; Kaeberlein et al., 1999).”
BackgroundCellular and molecular effects of sirtuins in health and disease
Horio, Y., Hayashi, T., Kuno, A., & Kunimoto, R. (2011) · Clinical Science · doi:10.1042/cs20100587 · Cited by 138
sirt1-null mice develop an autoimmune-like condition
Sequeira, J., Boily, G., Bazinet, S., Saliba, S., He, X., Jardine, K. E., Kennedy, C., Staines, W. A., Rousseaux, C. G., Mueller, R., et al. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.07.011 · Cited by 140
The Critical Role of SIRT1 in Parkinson’s Disease: Mechanism and Therapeutic Considerations
Li, X., Feng, Y., Wang, X.-X., Truong, D., & Wu, Y. (2020) · Aging and Disease · doi:10.14336/ad.2020.0216 · Cited by 134
Zhao, Y., Luo, P., Guo, Q., Li, S., Zhang, L., Zhao, M., Xu, H., Yang, Y., Poon, W. S., & Fei, Z. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2012.07.004 · Cited by 135
“Sir2 is an NAD-dependent deacetylase that connects metabolism with longevity in yeast (Kaeberlein et al., 1999).”
Saarikangas, J., & Barral, Y. (2015) · eLife · doi:10.7554/elife.06197 · Cited by 138
“Notably, Sir2 is also a key player in processes that underlie the asymmetric segregation of damaged mitochondria (Higuchi et al., 2013) and the accumulation of extrachromosomal DNA circles (Sinclair and Guarente, 1997; Kaeberlein et al., 1999) to the aging mother cell.”
BackgroundNew Insights into the Role of Histone Changes in Aging
Yi, S.-J., & Kim, K. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218241 · Cited by 134
“During replicative yeast aging, sir2 mutants exhibit a shortened lifespan [88].”
BackgroundDNA Methyltransferase Gene dDnmt2 and Longevity of Drosophila
Lin, M.-J., Tang, L.-Y., Reddy, M. N., & Shen, C. ‐. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.c400477200 · Cited by 136
Chronological Aging in Saccharomyces cerevisiae
Longo, V. D., & Fabrizio, P. (2011) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-94-007-2561-4_5 · Cited by 139
Regulation of SIRT1 protein levels by nutrient availability
Kanfi, Y., Peshti, V., Gozlan, Y. M., RATHAUS, M., Gil, R., & Cohen, H. Y. (2008) · FEBS Letters · doi:10.1016/j.febslet.2008.06.005 · Cited by 130
“Mutation in ySir2 shortens the yeast replicative life span by 40%, whereas increasing the activity of ySir2, using either genetic [1] or chemical means [2], extends yeast life span by a similar extent.”
BackgroundEpigenetic regulation of aging stem cells
Pollina, E. A., & Brunet, A. (2011) · Oncogene · doi:10.1038/onc.2011.45 · Cited by 111
“SIRT1, one of the seven mammalian Sirtuins, is the mammalian ortholog of yeast protein SIR2 (Rine et al., 1979), which extends lifespan in yeast, worms and flies (Kaeberlein et al., 1999; Tissenbaum and Guarente, 2001; Rogina and Helfand, 2004; Wood et al., 2004).”
BackgroundInfluential“Clocks” in the NAD World: NAD as a metabolic oscillator for the regulation of metabolism and aging
Imai, S. (2009) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2009.10.024 · Cited by 134
Small molecule regulation of Sir2 protein deacetylases
Grubisha, O., Smith, B. C., & Denu, J. M. (2005) · FEBS Journal · doi:10.1111/j.1742-4658.2005.04862.x · Cited by 131
“Conversely, deletion of SIR2 increases the frequency of rDNA recombination 10-fold [62] and shortens lifespan by 50% [ 7 ].”
BackgroundInfluentialSIR Proteins and the Assembly of Silent Chromatin in Budding Yeast
Kueng, S., Oppikofer, M., & Gasser, S. M. (2013) · Annual Review of Genetics · doi:10.1146/annurev-genet-021313-173730 · Cited by 132
Model Organisms as a Guide to Mammalian Aging
Tissenbaum, H. A., & Guarente, L. (2002) · Developmental Cell · doi:10.1016/s1534-5807(01)00098-3 · Cited by 128
Self-citationThe Role of SIRT6 Protein in Aging and Reprogramming of Human Induced Pluripotent Stem Cells
Sharma, A. S., Diecke, S., Zhang, W. Y., Lan, F., He, C., Mordwinkin, N. M., Chua, K. F., & Wu, J. C. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.405928 · Cited by 131
“In studies with Saccharomyces cerevisiae (6) and other organisms (7), these proteins were identified as key regulators of life span.”
BackgroundMorris, K. C., Lin, H. W., Thompson, J. W., & Pérez‐Pinzón, M. A. (2011) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2010.229 · Cited by 131
“…Metabolism (2011) 31, 1003–1019 & 2011 ISCBFM All rights reserved 0271-678X/11 $32.00 www.jcbfm.com The evidence linking sirtuins to longevity was first discovered in yeast in which overexpression of Sir2 prolonged life, whereas Sir2 mutants displayed a shortened lifespan (Kaeberlein et al, 1999).”
BackgroundInfluentialSIRT1 Promotes Differentiation of Normal Human Keratinocytes
Blander, G., Bhimavarapu, A., Mammone, T., Maes, D. H., Elliston, K. O., Reich, C., Matsui, M. S., Guarente, L., & Loureiro, J. (2008) · Journal of Investigative Dermatology · doi:10.1038/jid.2008.179 · Cited by 131
Self-citationDrugs that modulate aging: the promising yet difficult path ahead
Kennedy, B. K., & Pennypacker, J. K. (2014) · Translational research · doi:10.1016/j.trsl.2013.11.007 · Cited by 127
“M AN US CR IP T AC CE PT ED Abbreviations: FDA = Food and Drug Administration; IGF = Insulin-like Growth Factor; SIR2 = Silent Information Regulator Two; IIS = Insulin/IGF Signaling; PKA = Protein Kinase A; mTOR = Mammalian Target Of Rapamycin; TORC1 = Target of Rapamycin Complex 1; TORC2 = Target of Rapamycin Complex…”
BackgroundInfluentialIntracellular distribution of human SIRT 7 and mapping of the nuclear/nucleolar localization signal
Kiran, S., Chatterjee, N., Singh, S., Kaul, S. C., Wadhwa, R., & Ramakrishna, G. (2013) · FEBS Journal · doi:10.1111/febs.12346 · Cited by 125
Actin Dynamics Affect Mitochondrial Quality Control and Aging in Budding Yeast
Higuchi‐Sanabria, R., Vevea, J., Swayne, T. C., Chojnowski, R., Hill, V. M., Boldogh, I. R., & Pon, L. A. (2013) · Current Biology · doi:10.1016/j.cub.2013.10.022 · Cited by 129
Silent information regulator (Sir)T1 inhibits NF-κB signaling to maintain normal skeletal remodeling
Edwards, J., Perrien, D. S., Fleming, N., Nyman, J. S., Ono, K., Connelly, L., Moore, M. M., Lwin, S. T., Yull, F. E., Mundy, G. R., et al. (2012) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1824 · Cited by 127
Erjavec, N., & Nyström, T. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701634104 · Cited by 127
Chromatin structure and transposable elements in organismal aging
Wood, J. G., & Helfand, S. L. (2013) · Frontiers in Genetics · doi:10.3389/fgene.2013.00274 · Cited by 131
“This review summarizes the recent evidence linking chromatin structure and function to aging, with a particular focus on the relationship of heterochromatin structure to organismal aging.”
BackgroundAge-Associated Molecular Changes in the Kidney in Aged Mice
Lim, J. H., Kim, E. N., Kim, M. Y., Chung, S., Shin, S. J., Kim, H. W., Yang, C. W., Kim, Y., Chang, Y. S., Park, C. W., et al. (2012) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2012/171383 · Cited by 126
A Method for High-Throughput Quantitative Analysis of Yeast Chronological Life Span
Murakami, C. J., Burtner, C. R., Kennedy, B. K., & Kaeberlein, M. R. (2008) · The Journals of Gerontology Series A · doi:10.1093/gerona/63.2.113 · Cited by 124
“It was initially proposed that the increased RLS associated with DR was mediated by activation of the Sir2 histone deacetylase (5), which has been shown to promote longevity in yeast (7), worms (8), and flies (9).”
BackgroundSelf-citationDeep proteome analysis identifies age-related processes in C. elegans
Narayan, V., Ly, T., Pourkarimi, E., Murillo, A. B., Gartner, A., Lamond, A. I., & Kenyon, C. (2016) · Cell Systems · doi:10.1016/j.cels.2016.06.011 · Cited by 127
“These appear to be biological exceptions, as both proteins are positive regulators of longevity (Kaeberlein et al., 1999; Masse et al., 2005; Schmeisser et al., 2013).”
BackgroundPolarity and Differential Inheritance—Universal Attributes of Life?
Macara, I. G., & Mili, S. (2008) · Cell · doi:10.1016/j.cell.2008.11.006 · Cited by 128
“Deletion of sir2, in contrast, increases ERC formation and substantially reduces longevity (Kaeberlein et al., 1999).”
SIRT1 regulates macrophage self‐renewal
Imperatore, F., Maurizio, J., Aguilar, S. V., Busch, C. J., Favret, J., Kowenz‐Leutz, E., Cathou, W., Gentek, R., Perrin, P., Leutz, A., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201695737 · Cited by 127
“The founding member of this family, silent information regulator 2 (SIR2) from Saccharomyces cerevisia , was found to extend the replicative life span of yeast (Sinclair & Guarente, 1997; Kaeberlein et al , 1999).”
Extrachromosomal circular DNA: biogenesis, structure, functions and diseases
Yang, L., Jia, R., Ge, T., Ge, S., Zhuang, A., Chai, P., & Fan, X. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01176-8 · Cited by 136
Nicotinamide enhances mitochondria quality through autophagy activation in human cells
Kang, H. T., & Hwang, E. S. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00487.x · Cited by 128
“Yeast Sir2 and its homologues in C. elegans and Drosophila extend lifespan when over-expressed (Kaeberlein et al., 1999; Rogina, et al., 2002), and NAM treatment Correspondence Eun Seong Hwang, Department of Life Science, University of Seoul, Dongdaemungu, Jeonnongdong 90, Seoul, Republic of Korea…”
BackgroundZhao, Y., Sun, H., Lü, J., Li, X., Chen, X., Tao, D., Huang, W., & Huang, B. (2005) · Journal of Experimental Biology · doi:10.1242/jeb.01439 · Cited by 125
“In Saccharomyces cerevisiae, sir2 and rpd3, which encode two important histone deacetylases, were found to be involved in the regulation of lifespan, and deletion of sir2 shortened the lifespan (Kaeberlein et al., 1999), while the rpd3 knockout increased lifespan (Kim et al.”
BackgroundInfluentialOgura, M., Nakamura, Y., Tanaka, D., Zhuang, X., Fujita, Y., Obara, A., Hamasaki, A., Hosokawa, M., & Inagaki, N. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.01.081 · Cited by 121
Saccharomyces cerevisiae MPT5 and SSD1 Function in Parallel Pathways to Promote Cell Wall Integrity
Kaeberlein, M. R., & Guarente, L. (2002) · Genetics · doi:10.1093/genetics/160.1.83 · Cited by 124
Self-citationSirtuins in neurodegenerative diseases: an update on potential mechanisms
Min, S., Sohn, P., Cho, S.-H., Swanson, R. A., & Gan, L. (2013) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2013.00053 · Cited by 124
“Permalink https://escholarship.org/uc/item/0045385m Journal Frontiers in aging neuroscience, 5(SEP) ISSN 1663-4365 Authors Min, Sang-Won Sohn, Peter D Cho, Seo-Hyun et al. Publication Date 2013-09-25 DOI 10.3389/fnagi.2013.00053 Peer reviewed eScholarship.org Powered by the California Digital…”
BackgroundInfluentialRegulation of chronological aging in Schizosaccharomyces pombe by the protein kinases Pka1 and Sck2
Roux, A. E., Quissac, A., Chartrand, P., Ferbeyre, G., & Rokeach, L. A. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00225.x · Cited by 123
“Overexpression of the NAD + - dependent deacetylases Sir2 and Hst2 extends the replicative potential of yeast cells and reduces the accumulation of rDNA circles (Kaeberlein et al ., 1999; Lamming et al ., 2005).”
BackgroundEarly Telomerase Inactivation Accelerates Aging Independently of Telomere Length
Xie, Z., Jay, K. A., Smith, D. L., Zhang, Y., Liu, Z., Zheng, J., Tian, R., Li, H., & Blackburn, E. H. (2015) · Cell · doi:10.1016/j.cell.2015.02.002 · Cited by 126
“For example, Sir2 overexpression has been shown to increase mother cell lifespan (Kaeberlein et al., 1999).”
BackgroundMetabolic reprogramming of human CD8+ memory T cells through loss of SIRT1
Jeng, M. Y., Hull, P. A., Fei, M., Kwon, H.-S., Tsou, C.-L., Kasler, H., Ng, C.-P., Gordon, D. E., Johnson, J., Krogan, N., et al. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20161066 · Cited by 121
“Enhancing the expression of the ancestral SIR2 protein in yeast and worms promotes organismal life span extension (Kaeberlein et al., 1999; Tissenbaum and Guarente, 2001).”
BackgroundJayasena, T., Poljak, A., Smythe, G. A., Braidy, N., Münch, G. W., & Sachdev, P. S. (2013) · Ageing Research Reviews · doi:10.1016/j.arr.2013.06.003 · Cited by 122
Caloric restriction-induced life extension of rats and mice: A critique of proposed mechanisms
Masoro, E. J. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.02.011 · Cited by 120
“[89] reported that Sir2, a sirtuin protein deacetylase, enhances the replicative life span of Saccharomyces cerevisiae.”
Background
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
