The DOI matches its Crossref record; 63 of the 64 references it cites were found in a registry or an index.
SIRT1 Acts as a Nutrient-sensitive Growth Suppressor and Its Loss Is Associated with Increased AMPK and Telomerase Activity
Open accessAbstract
SIRT1, the mammalian homolog of SIR2 in Saccharomyces cerevisiae, is an NAD-dependent deacetylase implicated in regulation of lifespan. By designing effective short hairpin RNAs and a silent shRNA-resistant mutant SIRT1 in a genetically defined system, we show that efficient inhibition of SIRT1 in telomerase-immortalized human cells enhanced cell growth under normal and nutrient limiting conditions. Hematopoietic stem cells obtained from SIRT1-deficient mice also showed increased growth capacity and decreased dependency on growth factors. Consistent with this, SIRT1 inhibition was associated with increased telomerase activity in human cells. We also observed a significant increase in AMPK levels up on SIRT1 inhibition under glucose limiting conditions. Although SIRT1 suppression cooperated with hTERT to promote cell growth, either overexpression or suppression of SIRT1 alone had no effect on life span of human diploid fibroblasts. Our findings challenge certain models and connect nutrient sensing enzymes to the immortalization process. Furthermore, they show that in certain cell lineages, SIRT1 can act as a growth suppressor gene.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Signaling pathways related to nutrient sensing and uptake, such as SIRT1, AMPK and FoxO, may represent molecular effectors of the benefits of CR on stem cell activity113,114, although a complete understanding of how CR affects stem cell function must await further studies.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [113]
Citations
Cites
The serial cultivation of human diploid cell strains
Hayflick, L., & Moorhead, P. S. (1961) · Experimental Cell Research · doi:10.1016/0014-4827(61)90192-6 · Cited by 8,508
Specific Association of Human Telomerase Activity with Immortal Cells and Cancer
Kim, N. W., Piatyszek, M. A., Prowse, K. R., Harley, C. B., West, M. D., Ho, P. L. C., Coviello, G. M., Wright, W. E., Weinrich, S. L., & Shay, J. W. (1994) · Science · doi:10.1126/science.7605428 · Cited by 7,091 · cited 1×
“Consistent with this model telomerase is reactivated in immortal human cells (Counter et al., 1992; Kim et al., 1994).”
BackgroundTelomeres shorten during ageing of human fibroblasts
Harley, C. B., Futcher, A. B., & Greider, C. W. (1990) · Nature · doi:10.1038/345458a0 · Cited by 5,750
Extension of Life-Span by Introduction of Telomerase into Normal Human Cells
Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C.-P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., & Wright, W. E. (1998) · Science · doi:10.1126/science.279.5349.349 · Cited by 4,975
Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
Imai, S.-I., Armstrong, C. M., Kaeberlein, M., & Guarente, L. (2000) · Nature · doi:10.1038/35001622 · Cited by 3,510
Identification of a specific telomere terminal transferase activity in tetrahymena extracts
Greider, C. W., & Blackburn, E. H. (1985) · Cell · doi:10.1016/0092-8674(85)90170-9 · Cited by 3,400
Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase
Brunet, A., Sweeney, L. B., Sturgill, J. F., Chua, K. F., Greer, P. L., Lin, Y., Tran, H., Ross, S. E., Mostoslavsky, R., Cohen, H. Y., et al. (2004) · Science · doi:10.1126/science.1094637 · Cited by 3,239
Kiel, M. J., Yilmaz, Ö. H., Iwashita, T., Yilmaz, O. H., Terhorst, C., & Morrison, S. J. (2005) · Cell · doi:10.1016/j.cell.2005.05.026 · Cited by 3,168
Modulation of NF‐κB‐dependent transcription and cell survival by the SIRT1 deacetylase
Yeung, F., Hoberg, J. E., Ramsey, C. S., Keller, M. D., Jones, D. R., Frye, R. A., & Mayo, M. W. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600244 · Cited by 2,750
hSIR2SIRT1 Functions as an NAD-Dependent p53 Deacetylase
Vaziri, H., Dessain, S. K., Eaton, E. N., Imai, S., Frye, R. A., Pandita, T. K., Guarente, L., & Weinberg, R. A. (2001) · Cell · doi:10.1016/s0092-8674(01)00527-x · Cited by 2,690
Self-citationTelomerase Catalytic Subunit Homologs from Fission Yeast and Human
Nakamura, T. M., Morin, G. B., Chapman, K. B., Weinrich, S. L., Andrews, W. H., Lingner, J., Harley, C. B., & Cech, T. R. (1997) · Science · doi:10.1126/science.277.5328.955 · Cited by 2,256
Kaeberlein, M., McVey, M., & Guarente, L. (1999) · Genes & Development · doi:10.1101/gad.13.19.2570 · Cited by 2,253 · cited 2×
“Increased dosage of SIR2 extends replicative lifespan in certain strains of S. cerevisiae (Kaeberlein et al., 1999) and increases longevity of Caenorhabditis elegans (Tissenbaum and Guarente, 2001).”
BackgroundThe RNA Component of Human Telomerase
Feng, J., Funk, W. D., Wang, S.-S., Weinrich, S. L., Avilion, A. A., Chiu, C.-P., Adams, R. R., Chang, E., Allsopp, R. C., Yu, J., et al. (1995) · Science · doi:10.1126/science.7544491 · Cited by 2,227
Self-citationTelomere length predicts replicative capacity of human fibroblasts.
Allsopp, R. C., Vaziri, H., Patterson, C., Goldstein, S., Younglai, E. V., Futcher, A. B., Greider, C. W., & Harley, C. B. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.21.10114 · Cited by 2,200
Self-citationTelomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA
Blasco, M. A., Lee, H.-W., Hande, M. P., Samper, E., Lansdorp, P. M., DePinho, R. A., & Greider, C. W. (1997) · Cell · doi:10.1016/s0092-8674(01)80006-4 · Cited by 2,108
Counter, C. M., Avilion, A. A., LeFeuvre, C. E., Stewart, N. G., Greider, C. W., Harley, C. B., & Bacchetti, S. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05245.x · Cited by 2,096 · cited 1×
“Consistent with this model telomerase is reactivated in immortal human cells (Counter et al., 1992; Kim et al., 1994).”
BackgroundNegative Control of p53 by Sir2α Promotes Cell Survival under Stress
Luo, J., Nikolaev, A. Y., Imai, S.-I., Chen, D., Su, F., Shiloh, A., Guarente, L., & Gu, W. (2001) · Cell · doi:10.1016/s0092-8674(01)00524-4 · Cited by 2,081
Calorie 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
Meyerson, M., Counter, C. M., Eaton, E. N., Ellisen, L. W., Steiner, P., Caddle, S. D., Ziaugra, L., Beijersbergen, R. L., Davidoff, M. J., Liu, Q., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80538-3 · Cited by 1,784
Lin, S.-J., Defossez, P.-A., & Guarente, L. (2000) · Science · doi:10.1126/science.289.5487.2126 · Cited by 1,775
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 1,603
Morin, G. B. (1989) · Cell · doi:10.1016/0092-8674(89)90035-4 · Cited by 1,495
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
Essential role of mouse telomerase in highly proliferative organs
Lee, H.-W., Blasco, M. A., Gottlieb, G. J., Horner, J. W., Greider, C. W., & DePinho, R. A. (1998) · Nature · doi:10.1038/33345 · Cited by 1,270 · cited 1×
“Inactivation of telomerase in Mus musculus has revealed roles in cell survival and maintenance of genomic integrity via telomere maintenance (Blasco et al., 1997; Lee et al., 1998).”
BackgroundControl of telomere length by the human telomeric protein TRF1
van Steensel, B., & de Lange, T. (1997) · Nature · doi:10.1038/385740a0 · Cited by 1,219
Cell intrinsic alterations underlie hematopoietic stem cell aging
Rossi, D. J., Bryder, D., Zahn, J. M., Ahlenius, H., Sonu, R., Wagers, A. J., & Weissman, I. L. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503280102 · Cited by 1,152 · cited 3×
“To extend our findings to a more physiological system, we assayed the effect of SIRT1 deficiency on the establishment of the primitive HSC compartment, by quantitating the total number of HSCs and multipotent progenitors in BM from young (3–9 wk) Sirt1 knockout (Sirt11 / ) and control mice by flow cytometry using rigo…”
BackgroundMethodSelf-citationEvidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age.
Vaziri, H., Dragowska, W., Allsopp, R. C., Thomas, T. E., Harley, C. B., & Lansdorp, P. M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.21.9857 · Cited by 1,132
Self-citationPot1, the Putative Telomere End-Binding Protein in Fission Yeast and Humans
Baumann, P., & Cech, T. R. (2001) · Science · doi:10.1126/science.1060036 · Cited by 1,028
Vaziri, H., & Benchimol, S. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70109-5 · Cited by 1,003
Self-citationHuman SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin.
Vaquero, A., Scher, M., Lee, D., Erdjument-Bromage, H., Tempst, P., & Reinberg, D. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.08.031 · Cited by 916
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
Regulation of Telomerase by Telomeric Proteins
Smogorzewska, A., & de Lange, T. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.071403.160049 · Cited by 813
Resveratrol 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
Kim, N. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.13.2595 · Cited by 688
Nutrient Availability Regulates SIRT1 Through a Forkhead-Dependent Pathway
Nemoto, S., Fergusson, M. M., & Finkel, T. (2004) · Science · doi:10.1126/science.1101731 · Cited by 671
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 663
Acetylation of the C Terminus of Ku70 by CBP and PCAF Controls Bax-Mediated Apoptosis
Cohen, H. Y., Lavu, S., Bitterman, K. J., Hekking, B., Imahiyerobo, T. A., Miller, C. M., Frye, R. A., Ploegh, H. L., Kessler, B. M., & Sinclair, D. A. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00094-2 · Cited by 594
Tanner, K. G., Landry, J. W., Sternglanz, R., & Denu, J. M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.250422697 · Cited by 557
Moretti, P. M., Freeman, K., Coodly, L. R., & Shore, D. (1994) · Genes & Development · doi:10.1101/gad.8.19.2257 · Cited by 547
Human telomerase contains evolutionarily conserved catalytic and structural subunits
Harrington, L., Zhou, W., McPhail, T., Oulton, R., Yeung, D. S. K., Mar, V., Bass, M. B., & Robinson, M. O. (1997) · Genes & Development · doi:10.1101/gad.11.23.3109 · Cited by 465
Sir2-Independent Life Span Extension by Calorie Restriction in Yeast
Kaeberlein, M., Kirkland, K. T., Fields, S., & Kennedy, B. K. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020296 · Cited by 441
Ota, H., Tokunaga, E., Chang, K., Hikasa, M., Iijima, K., Eto, M., Kozaki, K., Akishita, M., Ouchi, Y., & Kaneki, M. (2005) · Oncogene · doi:10.1038/sj.onc.1209049 · Cited by 433
Sirt1 modulates premature senescence-like phenotype in human endothelial cells
Ota, H., Akishita, M., Eto, M., Iijima, K., Kaneki, M., & Ouchi, Y. (2007) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2007.08.008 · Cited by 429
Salt, I. P., JOHNSON, G., Ashcroft, S. J. H., & Hardie, D. G. (1998) · Biochemical Journal · doi:10.1042/bj3350533 · Cited by 408
Active Regulator of SIRT1 Cooperates with SIRT1 and Facilitates Suppression of p53 Activity
Kim, E.-J., Kho, J.-H., Kang, M., & Um, S. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.08.030 · Cited by 400
Sir2 Blocks Extreme Life-Span Extension
Fabrizio, P., Gattazzo, C., Battistella, L., Wei, M., Cheng, C., McGrew, K., & Longo, V. D. (2005) · Cell · doi:10.1016/j.cell.2005.08.042 · Cited by 396
Chiu, C., Dragowska, W., Kim, N. W., Vaziri, H., Yui, J., Thomas, T. E., Harley, C. B., & Lansdorp, P. M. (1996) · STEM CELLS · doi:10.1002/stem.140239 · Cited by 388
Self-citationShamblott, M., Axelman, J., Littlefield, J., Blumenthal, P., Huggins, G., Cui, Y., Cheng, L.-Z., & Gearhart, J. (2001) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.98.1.113 · Cited by 343
Mills, K. D., Sinclair, D. A., & Guarente, L. (1999) · Cell · doi:10.1016/s0092-8674(00)80772-2 · Cited by 334
MAR1—A REGULATOR OF THE HM a AND HMα LOCI IN SACCHAROMYCES CEREVISIAE
Klar, A. J. S., Fogel, S., & Macleod, K. (1979) · Genetics · doi:10.1093/genetics/93.1.37 · Cited by 278
Rine, J., Strathern, J. N., Hicks, J. B., & Herskowitz, I. (1979) · Genetics · doi:10.1093/genetics/93.4.877 · Cited by 268
Yilmaz, Ö. H., Kiel, M. J., & Morrison, S. J. (2005) · Blood · doi:10.1182/blood-2005-05-2140 · Cited by 266
Mammalian SIRT1 limits replicative life span in response to chronic genotoxic stress
Chua, K. F., Mostoslavsky, R., Lombard, D. B., Pang, W. W., Saito, S., Franco, S., Kaushal, D., Cheng, H.-L., Fischer, M. R., Stokes, N., et al. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.06.007 · Cited by 258
Tanny, J. C., & Moazed, D. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.2.415 · Cited by 253
HST2 Mediates SIR2 -Independent Life-Span Extension by Calorie Restriction
Lamming, D. W., Latorre‐Esteves, M., Medvedik, O., Wong, S. N., Tsang, F. A., Wang, C., Lin, S.-J., & Sinclair, D. A. (2005) · Science · doi:10.1126/science.1113611 · Cited by 227
Human POT1 Facilitates Telomere Elongation by Telomerase
Colgin, L. M., Baran, K., Baumann, P., Cech, T. R., & Reddel, R. R. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00339-7 · Cited by 212
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
Haber, J. E., & George, J. P. (1979) · Genetics · doi:10.1093/genetics/93.1.13 · Cited by 137
DNA damage triggers disruption of telomeric silencing and Mec1p-dependent relocation of Sir3p
McAinsh, A. D., Scott-Drew, S., Murray, J. A. H., & Jackson, S. P. (1999) · Current Biology · doi:10.1016/s0960-9822(99)80424-2 · Cited by 115
Effect of caloric restriction on age-associated cancers
Weindruch, R. H. (1992) · Experimental Gerontology · doi:10.1016/0531-5565(92)90012-o · Cited by 103
Comment on " HST2 Mediates SIR2 -Independent Life-Span Extension by Calorie Restriction"
Kaeberlein, M. R., Steffen, K. K., Hu, D., Dang, N., Kerr, E. O., Tsuchiya, M., Fields, S., & Kennedy, B. K. (2006) · Science · doi:10.1126/science.1124608 · Cited by 70
MATING TYPE AND SPORULATION IN YEAST I. MUTATIONS WHICH ALTER MATING-TYPE CONTROL OVER SPORULATION
Hopper, A. K., & Hall, B. D. (1975) · Genetics · doi:10.1093/genetics/80.1.41 · Cited by 64
Allsopp, R., Cheshier, S. H., & Weissman, I. L. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20021003 · Cited by 37
Self-citation
Flagged first, then by citations
1 of the 64 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Mammalian Sirtuins: Biological Insights and Disease Relevance
Haigis, M. C., & Sinclair, D. A. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathol.4.110807.092250 · Cited by 2,085
Stem cell aging: mechanisms, regulators and therapeutic opportunities
Oh, J., Lee, Y. D., & Wagers, A. J. (2014) · Nature Medicine · doi:10.1038/nm.3651 · Cited by 796
AMP-activated protein kinase-deficient mice are resistant to the metabolic effects of resveratrol
Um, J.-H., Park, S.-J., Kang, H., Yang, S., Foretz, M., McBurney, M. W., Kim, M. K., Viollet, B., & Chung, J. H. (2010) · Diabetes · doi:10.2337/db09-0482 · Cited by 647
The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth.
Firestein, R., Blander, G., Michan, S., Oberdoerffer, P., Ogino, S., Campbell, J., Bhimavarapu, A., Luikenhuis, S., de Cabo, R., Fuchs, C., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002020 · Cited by 588
The molecular targets of resveratrol
Kulkarni, S. S., & Cantó, C. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.10.005 · Cited by 477
Metadata
- Authors
- Narala, S. R., Allsopp, R. C., Wells, T. B., Zhang, G., Prasad, P., Coussens, M. J., Rossi, D. J., Weissman, I. L., & Vaziri, H.
- Affiliations
- University of Toronto (CA)
- University of Hawaiʻi at Mānoa (US)
- Institute for Stem Cell Biology and Regenerative Medicine (US)
- Venue
- Molecular Biology of the Cell
- Published
- 2008-03
- Volume
- 19
- Issue
- 3
- Pages
- 1210-1219
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC2262963
- OpenAlex
- W2145650048
- Cited by
- 106
- References
- 64
- Citations by year
- 2024: 1 · 2023: 4 · 2022: 1 · 2021: 5 · 2020: 2 · 2019: 1 · 2018: 6 · 2017: 4 · 2016: 3 · 2015: 9 · 2014: 11 · 2013: 9 · 2012: 8
- FWCI
- 5.71
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Biology of the Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Canadian Institutes of Health Research
- National Center for Research Resources (P20RR16467-05, P20RR016467)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- SIRT1, NAD+-dependent deacetylase, growth inhibition, nutrient sensing, AMPK, telomerase activity, hTERT, cell immortalization, hematopoietic stem cells, glucose limitation, lifespan, NAD+ metabolism, shRNA knockdown
- MeSH terms
- Animals, Cell Line, Cell Survival, Food, Glucose, Hematopoietic Stem Cells, Humans, Multienzyme Complexes, Protein Serine-Threonine Kinases, Telomerase, Sirtuins, Cell Proliferation, Mice, AMP-Activated Protein Kinases, Sirtuin 1
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
