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.
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
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?
Loss of Sir2 increases rDNA recombination and shortens life span.
“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
An extra genomic copy of Sir2 increases rDNA stability and extends life span.
“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
Increasing Sir2 level in yeast increases lifespan.
“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.
Cites
Sikorski, R. S., & Hieter, P. (1989) · Genetics · doi:10.1093/genetics/122.1.19 · Cited by 8,685 · 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-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 1,345 · see citing works
Johnson, F. B., Sinclair, D. A., & Guarente, L. (1999) · Cell · doi:10.1016/s0092-8674(00)80567-x · Cited by 840 · see citing works
Self-citationMoore, J. K., & Haber, J. E. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.5.2164 · Cited by 728 · see citing works
Rine, J., & Herskowitz, I. (1987) · Genetics · doi:10.1093/genetics/116.1.9 · Cited by 711 · see citing works
Aparicio, O. M., Billington, B. L., & Gottschling, D. E. (1991) · Cell · doi:10.1016/0092-8674(91)90049-5 · Cited by 704 · see citing works
Boulton, S. J., & Jackson, S. P. (1998) · The EMBO Journal · doi:10.1093/emboj/17.6.1819 · Cited by 641 · see citing works
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 · see citing works
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 · see citing works
A replication fork barrier at the 3′ end of yeast ribosomal RNA genes
Brewer, B. J., & Fangman, W. L. (1988) · Cell · doi:10.1016/0092-8674(88)90222-x · Cited by 552 · see citing works
Gottlieb, S., & Esposito, R. E. (1989) · Cell · doi:10.1016/0092-8674(89)90681-8 · Cited by 545 · see citing works
Boulton, S. J., & Jackson, S. P. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00890.x · Cited by 502 · see citing works
Mutation in the silencing gene S/R4 can delay aging in S. cerevisiae
Kennedy, B. K., Austriaco, N. P. G., Zhang, J., & Guarente, L. (1995) · Cell · doi:10.1016/0092-8674(95)90499-9 · Cited by 499 · see citing works
Self-citationBoulton, S. J. (1996) · Nucleic Acids Research · doi:10.1093/nar/24.23.4639 · Cited by 488 · see citing works
Relocalization of telomeric Ku and SIR proteins in response to DNA strand breaks in yeast
Martin, S. G., Laroche, T., Suka, N., Grunstein, M., & Gasser, S. M. (1999) · Cell · doi:10.1016/s0092-8674(00)80773-4 · Cited by 464 · see citing works
Yeast Ku as a Regulator of Chromosomal DNA End Structure
Gravel, S., Larrivée, M., Labrecque, P., & Wellinger, R. J. (1998) · Science · doi:10.1126/science.280.5364.741 · Cited by 444 · see citing works
Yeast DNA ligase IV mediates non-homologous DNA end joining
Wilson, T. E., Grawunder, U., & Lieber, M. R. (1997) · Nature · doi:10.1038/41365 · Cited by 418 · 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-citationSIR3 and SIR4 proteins are required for the positioning and integrity of yeast telomeres
Palladino, F., Laroche, T., Gilson, É., Axelrod, A., Pillus, L., & Gasser, S. M. (1993) · Cell · doi:10.1016/0092-8674(93)90388-7 · Cited by 397 · see citing works
Kobayashi, T., Heck, D. J., Nomura, M., & Horiuchi, T. (1998) · Genes & Development · doi:10.1101/gad.12.24.3821 · Cited by 389 · see citing works
Kennedy, B. K., Gotta, M., Sinclair, D. A., Mills, K., McNabb, D. S., Murthy, M., Pak, S. M., Laroche, T., Gasser, S. M., & Guarente, L. (1997) · Cell · doi:10.1016/s0092-8674(00)80219-6 · Cited by 375 · see citing works
Self-citationTranscriptional silencing of Ty1 elements in the RDN1 locus of yeast.Preprint
Bryk, M., Banerjee, M., Murphy, M. N., Knudsen, K. E., Garfinkel, D. J., & Curcio, M. J. (1997) · Genes & Development · doi:10.1101/gad.11.2.255 · Cited by 373 · see citing works
Shaw, P., & Jordan, E. G. (1995) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cb.11.110195.000521 · Cited by 372 · see citing works
Mills, K. D., Sinclair, D. A., & Guarente, L. (1999) · Cell · doi:10.1016/s0092-8674(00)80772-2 · Cited by 334 · see citing works
Self-citationSilencing factors participate in DNA repair and recombination in Saccharomyces cerevisiae
Tsukamoto, Y., Kato, J.-I., & Ikeda, H. (1997) · Nature · doi:10.1038/42288 · Cited by 332 · see citing works
Loss of transcriptional silencing causes sterility in old mother cells of S. cerevisiae
Smeal, T., Claus, J., Kennedy, B., Cole, F., & Guarente, L. (1996) · Cell · doi:10.1016/s0092-8674(00)81038-7 · Cited by 308 · see citing works
Self-citationDaughter cells of Saccharomyces cerevisiae from old mothers display a reduced life span.
Kennedy, B. K., Austriaco, N. P. G., & Guarente, L. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.127.6.1985 · Cited by 305 · see citing works
Self-citationCloning and characterization of four SIR genes of Saccharomyces cerevisiae.
Ivy, J. M., Klar, A. J. S., & Hicks, J. B. (1986) · Molecular and Cellular Biology · doi:10.1128/mcb.6.2.688 · Cited by 294 · see citing works
The nucleolus: an organelle formed by the act of building a ribosome
Mélèse, T., & Xue, Z. (1995) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(95)80085-9 · Cited by 288 · see citing works
Direct evidence for SIR2 modulation of chromatin structure in yeast rDNA
Fritze, C. E., Verschueren, K., Strich, R., & Esposito, R. E. (1997) · The EMBO Journal · doi:10.1093/emboj/16.21.6495 · Cited by 277 · see citing works
Functional and dynamic aspects of the mammalian nucleolus
Scheer, U., & Benavente, R. (1990) · BioEssays · doi:10.1002/bies.950120104 · Cited by 277 · see citing works
The arrest of replication forks in the rDNA of yeast occurs independently of transcription
Brewer, B. J., Lockshon, D., & Fangman, W. L. (1992) · Cell · doi:10.1016/0092-8674(92)90355-g · Cited by 274 · see citing works
Teo, S., & Jackson, S. P. (1997) · The EMBO Journal · doi:10.1093/emboj/16.15.4788 · Cited by 259 · see citing works
Kobayashi, T., & Horiuchi, T. (1996) · Genes to Cells · doi:10.1046/j.1365-2443.1996.d01-256.x · Cited by 252 · see citing works
Localization of Sir2p: the nucleolus as a compartment for silent information regulators
Gotta, M., Strahl‐Bolsinger, S., Renauld, H., Laroche, T., Kennedy, B. K., Grunstein, M. R., & Gasser, S. M. (1997) · The EMBO Journal · doi:10.1093/emboj/16.11.3243 · Cited by 232 · see citing works
Simple Mendelian inheritance of the reiterated ribosomal DNA of yeast.
Petes, T. D., & Botstein, D. (1977) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.74.11.5091 · Cited by 199 · see citing works
Schär, P., Herrmann, G., Daly, G., & Lindahl, T. L. (1997) · Genes & Development · doi:10.1101/gad.11.15.1912 · Cited by 190 · see citing works
Philippsen, P., Thomas, M., Kramer, R. A., & Davis, R. W. (1978) · Journal of Molecular Biology · doi:10.1016/0022-2836(78)90086-4 · Cited by 167 · see citing works
Balcells, F. S. (1986) · Journal of Gerontology · doi:10.1093/geronj/41.5.685b · Cited by 167 · see citing works
Smith, J. S., Brachmann, C. B., Pillus, L., & Boeke, J. D. (1998) · Genetics · doi:10.1093/genetics/149.3.1205 · Cited by 165 · see citing works
Park, P. U., Defossez, P.-A., & Guarente, L. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.5.3848 · Cited by 155 · cited 5× · see citing works
“Deletion of RAD52, a gene required for homologous recombination, results in the absence of ERCs, thereby implicating a recombinational repair process in their formation (Park et al. 1999).”
BackgroundInfluentialSelf-citationGene conversion plays the major role in controlling the stability of large tandem repeats in yeast.
Gangloff, S., Zou, H., & Rothstein, R. J. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00517.x · Cited by 134 · see citing works
Schild, D. (1995) · Genetics · doi:10.1093/genetics/140.1.115 · Cited by 131 · see citing works
Yeast cell-type regulation of DNA repair
Åström, S. U., Okamura, S. M., & Rine, J. (1999) · Nature · doi:10.1038/16833 · Cited by 119 · see citing works
Kobayashi, T., Hidaka, M., Nishizawa, M., & Horiuchi, T. (1992) · Molecular and General Genetics MGG · doi:10.1007/bf00265431 · Cited by 118 · see citing works
Barnes, G., & Rio, D. C. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.3.867 · Cited by 102 · see citing works
Cloning and Characterization of Four SIR Genes of Saccharomyces cerevisiae
Ivy, J. M., Klar, A. J. S., & Hicks, J. B. (1986) · Molecular and Cellular Biology · doi:10.1128/mcb.6.2.688-702.1986 · Cited by 90 · see citing works
Heude, M., & Fabre, F. (1993) · Genetics · doi:10.1093/genetics/133.3.489 · Cited by 89 · see citing works
HDF2, the Second Subunit of the Ku Homologue from Saccharomyces cerevisiae
Feldmann, H. M., Driller, L., Meier, B., Mages, G., Kellermann, J., & Winnacker, E. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.44.27765 · Cited by 83 · see citing works
Physical constitution of ribosomal genes in common strains of Saccharomyces cerevisiae
Rustchenko, E. P., & Sherman, F. (1994) · Yeast · doi:10.1002/yea.320100904 · Cited by 31 · see citing works
Fasullo, M., Bennett, T. M., & Dave, P. (1999) · Mutation Research/DNA Repair · doi:10.1016/s0921-8777(98)00059-7 · Cited by 26 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982 · see citing works
“cerevisiae (Kaeberlein et al., 1999), and subsequent reports indicated that enhanced expression of the worm (sir-2.”
BackgroundTherapeutic potential of resveratrol: the in vivo evidence
Baur, J. A., & Sinclair, D. A. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2060 · Cited by 3,958 · see citing works
“In yeast, worms and flies, extra copies of the genes that encode sirtuins are associated with extended lifespa”
BackgroundSmall 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
“Together, these findings add to the body of evidence that yeast ageing is caused by genomic instabilit”
BackgroundTranscriptional 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-citationStress-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
Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1
Rodgers, J. T., Lerin, C., Haas, W., Gygi, S. P., Spiegelman, B. M., & Puigserver, P. (2005) · Nature · doi:10.1038/nature03354 · Cited by 3,160 · see citing works
“We show here that the Sir2 homologue, SIRT1—which modulates ageing in several specie”
BackgroundMammalian 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
Sirtuins as regulators of metabolism and healthspan
Houtkooper, R. H., Pirinen, E., & Auwerx, J. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3293 · Cited by 2,008 · see citing works
Sirt1 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
“The regulatory gene that mediates this programme is SIR2 , which promotes survival in yeas”
BackgroundSelf-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
“In yeast, the SIR2 gene determines the lifespan of mother cells, and adding an extra copy of SIR2 extends lifespa”
BackgroundSelf-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
Lin, S.-J., Defossez, P.-A., & Guarente, L. (2000) · Science · doi:10.1126/science.289.5487.2126 · Cited by 1,775 · see citing works
Self-citationSirtuins 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
Cantó, C., Menzies, K. J., & Auwerx, J. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.023 · Cited by 1,648 · see citing works
“Different nuclear sirtuin orthologs have been shown to influence lifespan in yeast, worms, flies, and mice (Bauer et al., 2009; Boily et al., 2008; Kaeberlein et al., 1999; Kanfi et al., 2012; Rogina and Helfand, 2004; Tissenbaum and Guarente, 2001).”
BackgroundGenomic Instability and Aging-like Phenotype in the Absence of Mammalian SIRT6
Mostoslavsky, R., Chua, K. F., Lombard, D. B., Pang, W. W., Fischer, M. R., Gellon, L., Liu, P., Mostoslavsky, G., Franco, S., Murphy, M. M., et al. (2006) · Cell · doi:10.1016/j.cell.2005.11.044 · Cited by 1,637 · see citing works
“S. cerevisiae Sir2 promotes longevity in yeast mother cells (Kaeberlein et al., 1999).”
Self-citationThe intersection between aging and cardiovascular disease
North, B. J., & Sinclair, D. A. (2012) · Circulation Research · doi:10.1161/circresaha.111.246876 · Cited by 1,585 · see citing works
Kinaan, M., Ding, H., & Triggle, C. R. (2015) · Medical Principles and Practice · doi:10.1159/000381643 · Cited by 1,515 · 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-citationRecent progress in the biology and physiology of sirtuins
Finkel, T., Deng, C., & Mostoslavsky, R. (2009) · Nature · doi:10.1038/nature08197 · Cited by 1,484 · see citing works
NAD+ 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-citationFrom 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
Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins
Frye, R. A. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3000 · Cited by 1,409 · see citing works
Michishita, E., Park, J. Y., Burneskis, J. M., Barrett, J. C., & Horikawa, I. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-01-0033 · Cited by 1,364 · see citing works
“Our data present a striking contrast to the lifespan extension in lower eukaryotes by Sir2 and its homologues (Kaeberlein et al., 1999; Tissenbaum and Guarente, 2001; Rogina and Helfand, 2004) and suggest complex layers of regulation of replicative aging in human cells.”
BackgroundResultInfluentialSir2 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
“, 1997; Sinclair and Guarente, 1997), and increased dosage of the yeast SIR2 gene extends the lifespan of mother cells beyond the wild-type (Kaeberlein et al., 1999).”
BackgroundSelf-citationGenetic 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
“Subsequent experiments validated the notion that the amount of Sir2 at the rDNA was predictive of life span; sir2 -deletion strains have a short life span, and strains with an extra SIR2 copy have super-extended life span”
Self-citationRegulation 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
Self-citationFOXO transcription factors at the interface between longevity and tumor suppression
Greer, E. L., & Brunet, A. (2005) · Oncogene · doi:10.1038/sj.onc.1209086 · Cited by 1,306 · see citing works
“In yeast, worms, and flies, expression of Sir2 extends longevity (Kaeberlein et al., 1999; Tissenbaum and Guarente, 2001; Rogina and Helfand, 2004; Wood et al., 2004).”
BackgroundMetabolic 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
“Genetic evidence for a role of Sir2 in this nutrient/aging pathway has been provided in model organisms such as yeast (Kaeberlein et al, 1999), worms (Tissenbaum and Guarente, 2001) and flies (Rogina and Helfand, 2004).”
BackgroundA role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis
Ahn, B.-H., Kim, H.-S., Song, S., Lee, I. H., Liu, J., Vassilopoulos, A., Deng, C.-X., & Finkel, T. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803790105 · Cited by 1,291 · see citing works
“Remarkably, increased dosage of Sir2 extends the life span of yeast as well as several other simple organisms (3, 4).”
BackgroundCalorie 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
“An extra copy of SIR2 extends life span in yeast, flies, and worms (Kaeberlein et al., 1999; Rogina and Helfand, 2004; Tissenbaum and Guarente, 2001).”
BackgroundMammalian 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
“In yeast, an extra copy of the SIR2 gene extends replicative lifespan by 50%, while deleting Sir2 shortens lifespan (Kaeberlein et al. 1999).”
BackgroundSelf-citationRegulation of pgc-1α, a nodal regulator of mitochondrial biogenesis
Fernandez-Marcos, P. J., & Auwerx, J. (2011) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.110.001917 · Cited by 1,237 · see citing works
Calnan, D. R., & Brunet, A. (2008) · Oncogene · doi:10.1038/onc.2008.21 · Cited by 1,170 · 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
“An extra copy of the yeast SIR2 gene extends replicative life span of mother cells compared to wild-type, while a deletion of SIR2 reduces life span (Kaeberlein et al., 1999).”
BackgroundSelf-citationPearson, 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
“Extra copies of SIR2 or its homologs extend life span in yeast (Kaeberlein et al., 1999), worms (Tissenbaum and Guarente, 2001), and flies (Rogina and Helfand, 2004), and are proposed to underlie some of the physiological effects of DR in simple organisms (Anderson et al., 2003; Lin et al., 2000)…”
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
“Soon after the discovery that SIR2 extended yeast replicative lifespan [3,4], the orthologs of SIR2 were proposed to carry out same lifespan prolonging effects in Caenorhabditis elegans [5,6], and in Drosophila melanogaster [7], and to mediate beneficial effects of calorie restriction (CR) on health and longevity[7–10…”
BackgroundSelf-citationAngiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology
Forrester, S. J., Booz, G. W., Sigmund, C. D., Coffman, T. M., Kawai, T., Rizzo, V., Scalia, R. G., & Eguchi, S. (2018) · Physiological Reviews · doi:10.1152/physrev.00038.2017 · Cited by 1,106 · see citing works
Increased Nuclear NAD Biosynthesis and SIRT1 Activation Prevent Axonal Degeneration
Araki, T., Sasaki, Y., & Milbrandt, J. (2004) · Science · doi:10.1126/science.1098014 · Cited by 1,060 · 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
“Studies from yeast identified the evolutionarily conserved NADþ -dependent deacetylase Sir2 as a critical regulator of the aging process (Kaeberlein et al, 1999; Imai et al, 2000; Anderson et al, 2003a, b; Howitz et al, 2003; Cohen et al, 2004b).”
BackgroundCalorie 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
“Deletion of SIR2 shortens lifespan and overexpression of SIR2 extends lifespa”
BackgroundSelf-citationMechanism of Human SIRT1 Activation by Resveratrol
Borra, M. T., Smith, B. C., & Denu, J. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501250200 · Cited by 1,065 · 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
“Moreover, this silencing and the ageing of replicating mother cells is determined by the SIR2 gen”
BackgroundSelf-citationBitterman, 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
Epigenetic mechanisms of longevity and aging
Sen, P., Shah, P. P., Nativio, R., & Berger, S. L. (2016) · Cell · doi:10.1016/j.cell.2016.07.050 · Cited by 956 · see citing works
Revollo, 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
A novel pathway regulates memory and plasticity via SIRT1 and miR-134
Gao, J., Wang, W.-Y., Mao, Y.-W., Gräff, J., Guan, J.-S., Pan, L., Mak, G., Kim, D., Su, S. C., & Tsai, L.-H. (2010) · Nature · doi:10.1038/nature09271 · Cited by 975 · 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
“Many genetic interventions that increase RLS, including those that lead to activation of the histone deacetylase Sir2 (Kaeberlein et al. 1999), do not have a similar effect on CLS (Fabrizio et al. 2005; Kennedy 2005), and some mutations have been reported to have opposite effects in the two life span assays (Harris et…”
BackgroundSelf-citationNAD+ 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
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
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
“*Correspondence: david_sinclair@hms.harvard.edu DOI 10.1016/j.cell.2007.07.035”
BackgroundInfluentialSRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1
Pacholec, M., Bleasdale, J. E., Chrunyk, B., Cunningham, D., Flynn, D., Garofalo, R. S., Griffith, D., Griffor, M., Loulakis, P., Pabst, B., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.088682 · Cited by 915 · 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
“In a seminal paper, it was shown that extra copies of Sir2 increased life span by 30%, whereas ablation of the Sir2 gene had the opposite effects, reducing life span by 50% (59).”
BackgroundRapamycin, But Not Resveratrol or Simvastatin, Extends Life Span of Genetically Heterogeneous Mice
Miller, R. A., Harrison, D. E., Astle, C. M., Baur, J. A., Boyd, A. R., de Cabo, R., Fernandez, E., Flurkey, K., Javors, M. A., Nelson, J. F., et al. (2011) · The Journals of Gerontology: Series A · doi:10.1093/gerona/glq178 · Cited by 896 · see citing works
“Resveratrol was chosen for study because of promising data (25) from animal models of cancer, heart disease, stroke, and immunity and because of data suggesting it could activate sirtuins, a class of protein deacetylases implicated in control of life span in yeast (26), flies (27), and worms (28).”
BackgroundButow, R. A., & Avadhani, N. G. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00179-0 · Cited by 882 · see citing works
Mattagajasingh, I., Kim, C.-S., Naqvi, A., Yamamori, T., Hoffman, T. A., Jung, S.-B., DeRicco, J., Kasuno, K., & Irani, K. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0704329104 · Cited by 881 · see citing works
The sirtuin family in health and disease
Wu, Q., Zhang, T., Chen, H., Yu, X., Lv, J.-L., Liu, Y., Liu, Y., Zheng, G., Zhao, J.-Q., Wei, Y., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01257-8 · Cited by 891 · see citing works
Pal, S., & Tyler, J. K. (2016) · Science Advances · doi:10.1126/sciadv.1600584 · Cited by 860 · see citing works
“Overexpression of Sir2 extends life span (99).”
AMP-Activated Protein Kinase (AMPK) Controls the Aging Process via an Integrated Signaling Network
Salminen, A., & Kaarniranta, K. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2011.12.005 · Cited by 860 · 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
“Additionally, yeast Sir2 functions in double-stranded DNA repair, regulation of mitotic and meiotic cell cycle progression, suppression of rDNA homologous recombination, chromosome stability and modulation of lifespan (Brachmann et al., 1995; Cockell and Gasser, 1999; Guarente, 1999; Haber, 1999; Kaeberlein et al., 19…”
BackgroundSIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging
Oberdoerffer, P., Michan, S., McVay, M., Mostoslavsky, R., Vann, J., Park, S.-K., Hartlerode, A., Stegmuller, J., Hafner, A., Loerch, P., et al. (2008) · Cell · doi:10.1016/j.cell.2008.10.025 · Cited by 852 · see citing works
“An additional copy of SIR2 (2xSIR2) extends replicative life span (Kaeberlein et al., 1999), but its effect on oxidative stress resistance and loss of silencing is unknown.”
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
The Role of Sirtuins in Antioxidant and Redox Signaling
Singh, C. K., Chhabra, G., Ndiaye, M. A., Garcia‐Peterson, L. M., Mack, N. J., & Ahmad, N. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7290 · Cited by 812 · see citing works
“In 1999, Kaeberlein and McVey showed that overexpression of Sir2 extended life span in yeast (67).”
BackgroundThe world of protein acetylation
Drazic, A., Myklebust, L. M., Ree, R., & Arnesen, T. (2016) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2016.06.007 · Cited by 798 · see citing works
“Initially, yeast sir2 overexpressionwas discovered to give yeast cells increased lifespan [434].”
BackgroundSenescence and aging: the critical roles of p53
Rufini, A., Tucci, P., Celardo, I., & Melino, G. (2013) · Oncogene · doi:10.1038/onc.2012.640 · Cited by 798 · 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
“The major genetic determinant of replicative life span a tin yeast to emerge from genetic studies is SIR2; lossof-function mutations shortened life span, and in- t Rcreased gene dosage extended it (Kaeberlein et al., 1999).”
BackgroundSIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle
Nakagawa, T., Lomb, D. J., Haigis, M. C., & Guarente, L. (2009) · Cell · doi:10.1016/j.cell.2009.02.026 · Cited by 787 · see citing works
“In yeast, C. elegans, and Drosophila, SIR2 orthologs slow aging and respond to metabolic conditions (Kaeberlein et al., 1999; Lin et al., 2002; Rogina and Helfand, 2004; Tissenbaum and Guarente, 2001; Wang et al., 2006).”
Self-citationHuman iPSC-based modeling of late-onset disease via progerin-induced aging
Miller, J. D., Ganat, Y. M., Kishinevsky, S., Bowman, R. L., Liu, B., Tu, E. Y., Mandal, P. K., Vera, E., Shim, J.-W., Kriks, S., et al. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.11.006 · Cited by 777 · see citing works
Sauve, A. A., Wolberger, C., Schramm, V. L., & Boeke, J. D. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.74.082803.133500 · Cited by 763 · 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
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
Self-citationHuman Ageing Genomic Resources: new and updated databases
Tacutu, R., Thornton, D., Johnson, E., Budovsky, A., Barardo, D., Craig, T., Diana, E., Lehmann, G., Toren, D., Wang, J., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gkx1042 · Cited by 738 · 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
“Cells with an additional copy of SIR2 live 30% longer than the wild type, whereas sir2Δ strains age prematurel”
BackgroundResveratrol stimulates AMP kinase activity in neurons
Dasgupta, B., & Milbrandt, J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610068104 · Cited by 723 · see citing works
SIRT1 transgenic mice show phenotypes resembling calorie restriction
Bordone, L., Cohen, D., Robinson, A., Motta, M. C., Van Veen, E., Czopik, A., Steele, A. D., Crowe, H., Marmor, S., Luo, J., et al. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00335.x · Cited by 722 · see citing works
“…Journal compilation © Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland 2007 764 Overexpression of Sir2 extends lifespan in yeast, C. elegans and Drosophila by a mechanism overlapping moderate CR (Kaeberlein et al., 1999; Tissenbaum & Guarente, 2001; Rogina & Helfand, 2004).”
BackgroundInfluentialSelf-citationThe 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
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
“In parallel with the work on calorie restriction, a genetic screen for long-lived mutants of Saccharomyces cerevisiae led to the discovery that the silent information regulation-2 (Sir2) gene could slow aging in this species (164, 306).”
BackgroundSchwer, 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
Sir2 links chromatin silencing, metabolism, and agingPreprint
Guarente, L. (2000) · Genes & Development · doi:10.1101/gad.14.9.1021 · Cited by 718 · see citing works
“These studies have led to the general conclusion that the silencing protein Sir2 is a limiting component of longevity; deletions of SIR2 shorten life span and an extra copy of this gene increases life span (Kaeberlein et al. 1999).”
BackgroundSelf-citationSirt1 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
“This gene regulates the life span in yeast [8] and Caenorhabditis elegans [9] as a longevity determinant.”
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
“In yeast, the sirtuin (SIR)2 gene mediates the life-extending effects of calorie restriction by nutrient withdrawal [84], although the overproduction of SIR2 enzyme can prolong the life of yeast grown under normal nutrient conditions [85].”
BackgroundSIRT1 and aging related signaling pathways
Chen, C., Zhou, M., Ge, Y., & Wang, X. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111215 · Cited by 693 · see citing works
Histone H4 lysine 16 acetylation regulates cellular lifespan
Dang, W., Steffen, K. K., Perry, R., Dorsey, J. A., Johnson, F. B., Shilatifard, A., Kaeberlein, M., Kennedy, B. K., & Berger, S. L. (2009) · Nature · doi:10.1038/nature08085 · Cited by 667 · see citing works
Self-citationNutrient 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
Loss of epigenetic information as a cause of mammalian aging
Yang, J.-H., Hayano, M., Griffin, P. T., Amorim, J. A., Bonkowski, M. S., Apostolides, J. K., Salfati, E. L., Blanchette, M., Munding, E. M., Bhakta, M., et al. (2023) · Cell · doi:10.1016/j.cell.2022.12.027 · Cited by 643 · 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
“H S s s o r d f ( f a s f c L a o a e i a s w ( l IC1 Directly Regulates SIRT1 Transcription ince Sir2 expression level is critical in influencing life pan of yeast and worm (Kaeberlein et al., 1999; Tisenbaum and Guarente, 2001), homeostatic regulation f this protein would seem essential.”
BackgroundInfluentialNAD+ homeostasis in health and disease
Katsyuba, E., Romani, M., Hofer, D., & Auwerx, J. (2020) · Nature Metabolism · doi:10.1038/s42255-019-0161-5 · Cited by 627 · see citing works
Asymmetric Inheritance of Oxidatively Damaged Proteins During Cytokinesis
Aguilaniu, H., Gustafsson, L., Rigoulet, M., & Nyström, T. (2003) · Science · doi:10.1126/science.1080418 · Cited by 642 · 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-citationEpigenetic regulation of ageing: linking environmental inputs to genomic stability
Benayoun, B. A., Pollina, E. A., & Brunet, A. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm4048 · Cited by 610 · 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
“In the absence of SIR2, the rate of ERC formation is enhanced and cells are short lived (Kaeberlein et al., 1999).”
BackgroundInfluentialMoynihan, 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
Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription
Ford, E., Voit, R., Liszt, G., Magin, C., Grummt, I., & Guarente, L. (2006) · Genes & Development · doi:10.1101/gad.1399706 · Cited by 629 · see citing works
“In yeast, Sir2p promotes longevity predominantly through its silencing role at the rDNA (Sinclair and Guarente 1997; Kaeberlein et al. 1999).”
BackgroundSelf-citationAbsence 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
Self-citationThe 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
“This effect of Sir2p is thought to be due to its ability to suppress recombination between tandem copies of the ribosomal genes, as aging mother cells show loss of ribosomal DNA, presumed to be due to recombinational excision from the genome (20).”
BackgroundDaitoku, 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
- 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
- Health Sciences › Medicine › Physiology › 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