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SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin
Open accessAbstract
The Sir2 deacetylase regulates chromatin silencing and lifespan in Saccharomyces cerevisiae. In mice, deficiency for the Sir2 family member SIRT6 leads to a shortened lifespan and a premature ageing-like phenotype. However, the molecular mechanisms of SIRT6 function are unclear. SIRT6 is a chromatin-associated protein, but no enzymatic activity of SIRT6 at chromatin has yet been detected, and the identity of physiological SIRT6 substrates is unknown. Here we show that the human SIRT6 protein is an NAD+-dependent, histone H3 lysine 9 (H3K9) deacetylase that modulates telomeric chromatin. SIRT6 associates specifically with telomeres, and SIRT6 depletion leads to telomere dysfunction with end-to-end chromosomal fusions and premature cellular senescence. Moreover, SIRT6-depleted cells exhibit abnormal telomere structures that resemble defects observed in Werner syndrome, a premature ageing disorder. At telomeric chromatin, SIRT6 deacetylates H3K9 and is required for the stable association of WRN, the factor that is mutated in Werner syndrome. We propose that SIRT6 contributes to the propagation of a specialized chromatin state at mammalian telomeres, which in turn is required for proper telomere metabolism and function. Our findings constitute the first identification of a physiological enzymatic activity of SIRT6, and link chromatin regulation by SIRT6 to telomere maintenance and a human premature ageing syndrome.
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TL;DR
Human SIRT6 is an NAD+-dependent histone H3 lysine 9 (H3K9) deacetylase that associates with telomeres in S phase and maintains low H3K9 acetylation there. SIRT6 depletion causes telomere dysfunction, chromosomal end-to-end fusions, and premature cellular senescence, and impairs WRN association at telomeric chromatin, linking SIRT6 to telomere maintenance and Werner syndrome-like defects.
Key findings
- SIRT6 knockdown in WI-38 human fibroblasts shortened replicative lifespan, causing premature senescence about ten population doublings before controls, with increased senescence-associated β-galactosidase staining; two independent SIRT6 shRNAs reproduced this, while irrelevant shRNAs did not.
- SIRT6-depleted cells showed elevated telomere dysfunction-induced foci, non-recurrent chromosomal end-to-end fusions that were more pronounced at later population doublings, and Werner syndrome-like telomere abnormalities including sister telomere loss, telomere doublets, and weak or absent telomere signals at fusion sites; mean telomere length was not significantly reduced.
- SIRT6 deacetylated H3K9Ac specifically among tested acetylated histone peptides, with no deacetylation detected for 12 other acetylated histone peptides; the catalytic mutant H133Y markedly decreased activity. SIRT6 knockdown caused H3K9 hyperacetylation at telomeric chromatin in S phase, and S6KO mouse cells also showed telomeric H3K9 hyperacetylation.
- SIRT6 was required for stable WRN association at telomeric chromatin; SIRT6 knockdown significantly inhibited WRN association in U2OS and IMR90 cells. Telomerase expression reversed premature senescence, whereas augmenting base excision repair did not, and low oxygen culture did not prevent senescence.
Methods
- Retrovirus-mediated shRNA knockdown of SIRT6 in WI-38, IMR90, U2OS, and HeLa cells, with replicative senescence assays, SA-β-gal staining, immuno-FISH TIF assays, metaphase cytogenetics/SKY/telomere FISH, and cell-cycle flow cytometry.
- Telomere chromatin immunoprecipitation (T-ChIP) after thymidine synchronization and release, using antibodies against SIRT6, Flag, WRN, and H3K9Ac, with telomeric DNA detected by slot blot.
- In vitro histone deacetylation assays with recombinant SIRT6 and acetylated histone tail peptides or full-length histones, including mass spectrometry; 293T cells were transfected with wild-type or H133Y SIRT6 and analyzed by Western blotting.
Limitations
- Stated: SIRT6 showed only modest in vitro deacetylation activity on H3K9Ac peptides, and no direct SIRT6-WRN interaction at chromatin was observed, although additional functional or physical interactions might exist.
- Stated: S6KO mouse cells showed telomeric H3K9 hyperacetylation but did not display the downstream cellular defects seen in human cells, which the authors attribute to the large functional reserve of mouse telomeres.
- Evident: many conclusions rely on shRNA knockdown and overexpression in cultured cells, and several supporting results are reported as “data not shown”; global H3K9Ac levels did not differ significantly, so the key effect is telomere-specific.
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“As controls, the association of Alu repeat sequences with SIRT6 ChIPs was not above background (Fig. 2b–d), and the SIRT6 T-ChIP signal was abolished in S6KD cells, validating the specificity of the signal (Fig. 2d).”
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“In both U2OS and IMR90 cells, SIRT6 knockdown significantly inhibited the association of WRN with telomeric chromatin (Fig. 4a, b, and data not shown).”
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“However, mean telomere length was not significantly reduced in S6KD cells (Supplementary Fig. 5).”
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“Inactivation of SIRT6 leads to H3K9 hyperacetylation at telomeric chromatin in both human and mouse cells, but the mouse cells do not display the downstream cellular defects observed in human cells, which is consistent with the large functional reserve of mouse telomeres (Supplementary Fig. 13d; data not shown)14,25.”
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“First, telomere stabilization (by the ectopic expression of telomerase (hTERT)) reversed the premature senescence of S6KD, whereas augmenting BER (by the ectopic expression of the DNA polymerase-β dRP lyase domain) did not (Fig. 1g and Supplementary Fig. 6).”
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“Inactivation of SIRT6 leads to H3K9 hyperacetylation at telomeric chromatin in both human and mouse cells, but the mouse cells do not display the downstream cellular defects observed in human cells, which is consistent with the large functional reserve of mouse telomeres (Supplementary Fig. 13d; data not shown)14,25.”
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“First, telomere stabilization (by the ectopic expression of telomerase (hTERT)) reversed the premature senescence of S6KD, whereas augmenting BER (by the ectopic expression of the DNA polymerase-β dRP lyase domain) did not (Fig. 1g and Supplementary Fig. 6).”
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“Analysis of TIFs revealed elevated telomere dysfunction in S6KD cells (Fig. 1d, e, and Supplementary Fig. 4a).”
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“Similarly, SIRT6 knockdown in U2OS cells resulted in delayed completion of S phase (Supplementary Fig. 14), which is consistent with a role for SIRT6 in modulating telomeres during replication.”
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“In contrast, investigation of histone acetylation status at telomeres in S-phase-enriched cultures by T-ChIP revealed H3K9 hyperacetylation in S6KD cells (Fig. 3d–f).”
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“Premature cellular senescence was also observed with two independent SIRT6 shRNAs, ruling out off-target shRNA effects, but not with irrelevant shRNAs (Supplementary Fig 2b–d and Supplementary Fig 3c).”
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“SIRT6 occupancy at telomeric chromatin was observed for both recombinant Flag-tagged SIRT6 (Fig. 2a, b) and endogenous SIRT6 (Fig. 2c, d), and in both U2OS osteosarcoma cells (Fig. 2b, c) and primary IMR90 cells (Fig. 2d).”
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“This activity was highly specific for H3K9Ac, because no deacetylation was detected for 12 other acetylated histone peptides (Fig. 3a and Supplementary Fig. 11).”
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“SIRT6 also deacetylated H3K9Ac, but not several other acetylated residues, in the context of purified full-length histone H3, and mutation of a conserved catalytic residue (H133Y) of SIRT6 markedly decreased this activity (Fig. 3b and data not shown).”
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“SIRT6 knockdown (S6KD) cells have a strikingly shortened replicative lifespan, undergoing premature cellular senescence about ten population doublings before control cells, and show increased levels of senescence-associated β-galactosidase (SA-β-gal) staining (Fig. 1b, c, and Supplementary Fig. 2a).”
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“Finally, SIRT6 efficiently and specifically deacetylated H3K9Ac (but not other acetylated histone residues) in 293T cells, whereas the mutant SIRT6 protein did not (Fig. 3c and Supplementary Fig. 12).”
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“Non-recurrent chromosomal end-to-end fusions were observed in S6KD cells and were more pronounced at later population doublings, but they were rarely observed in control cells (Fig. 1f and Supplementary Fig. 4b, c).”
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“First, S6KD metaphases showed elevated levels of missing telomere signals (sister telomere loss) and extra telomere signals (telomere doublets) (Fig. 4d–f), defects observed in WS cells and associated with aberrant telomere processing during replication8,13,20.”
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“Together, these observations suggest that S6KD cells undergo accelerated senescence and telomere dysfunction in response to stochastic telomere sequence loss, without increased global telomere erosion.”
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“We conclude that SIRT6 is crucial in maintaining a normal replicative life-span and in preventing the premature senescence of human cells.”
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“Together, these data locate SIRT6 at telomeric chromatin in S phase and suggest a potential role for SIRT6 in regulating replication-associated dynamics in telomere structure.”
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“Together, these findings suggest that SIRT6 collaborates with WRN at telomeric chromatin to ensure efficient telomere replication and to prevent the accrual of structural abnormalities at telomeres.”
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“Our study has identified a crucial function for SIRT6 in chromatin regulation at mammalian telomeres and provides a new mechanism by which the regulation of chromatin is linked to telomere function, cellular senescence and, potentially, organismal ageing.”
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“Together, these observations indicate that SIRT6 is an NAD-dependent deacetylase with specificity for H3K9Ac.”
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“We propose a model (Supplementary Fig. 1) in which the deacetylation of H3K9Ac by SIRT6 promotes the formation of a specialized telomeric chromatin state that is required for the stable association of S-phase-dependent telomere-processing factors such as WRN, to prevent aberrant sequence loss or metabolism of telomeres.”
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“Together, these findings demonstrate that telomere dysfunction, not BER defects or oxidative stress, underlie the premature senescence phenotype of S6KD cells.”
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“We propose that SIRT6 contributes to the propagation of a specialized chromatin state at mammalian telomeres, which in turn is required for proper telomere metabolism and function.”
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“Our findings constitute the first identification of a physiological enzymatic activity of SIRT6, and link chromatin regulation by SIRT6 to telomere maintenance and a human premature ageing syndrome.”
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The paper relies on this without support.
No enzymatic activity of SIRT6 at chromatin has yet been detected, and the identity of physiological SIRT6 substrates is unknown.
“SIRT6 is a chromatin-associated protein3, but no enzymatic activity of SIRT6 at chromatin has yet been detected, and the identity of physiological SIRT6 substrates is unknown.”
“Although no physiological enzymatic activity for SIRT6 on histones or other trans substrate has yet been observed, we proposed that SIRT6 might regulate chromatin at telomeres by deacetylating a specific histone tail residue.”
The paper relies on this without support.
No effect of SIRT6 deficiency on cellular lifespan has been reported.
“Despite the ageing-like phenotype of SIRT6-deficient mice, no effect of SIRT6 deficiency on cellular lifespan has been reported.”
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In the citing paper
“SIRT6 promotes DNA double strand break repair19,20, regulates telomere stability21, suppresses inflammation22 and opposes tumorigenesis23,24.”
From SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age (2014) · cites this paper as [21]
In the citing paper
“In human cells, loss of SIRT6, an H3K9 deacetylase that silences telomeres, causes telomere dysfunction and premature cellular senescence (Michishita et al., 2008).”
From The Aging Epigenome (2016) · cites this paper as Michishita et al., 2008
Citations
Cites
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477
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
A DNA damage checkpoint response in telomere-initiated senescence
Fagagna, F. D. D., Reaper, P. M., Clay-Farrace, L., Fiegler, H., Carr, P., von Zglinicki, T., Saretzki, G., Carter, N. P., & Jackson, S. P. (2003) · Nature · doi:10.1038/nature02118 · Cited by 2,917
Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors
Campisi, J. (2005) · Cell · doi:10.1016/j.cell.2005.02.003 · Cited by 2,379
Multicolor Spectral Karyotyping of Human Chromosomes
Schröck, E., du Manoir, S., Veldman, T., Schoell, B., Wienberg, J., Ferguson-Smith, M. A., Ning, Y., Ledbetter, D. H., Bar‐Am, I., Soenksen, D. G., et al. (1996) · Science · doi:10.1126/science.273.5274.494 · Cited by 1,753
Self-citationTRF2 Protects Human Telomeres from End-to-End Fusions
van Steensel, B., Smogorzewska, A., & de Lange, T. (1998) · Cell · doi:10.1016/s0092-8674(00)80932-0 · Cited by 1,709
Genomic 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
Self-citationDNA Damage Foci at Dysfunctional Telomeres
Takai, H., Smogorzewska, A., & de Lange, T. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00542-6 · Cited by 1,409
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
Self-citationHerbig, U., Jobling, W. A., Chen, B. P. C., Chen, D. J., & Sedivy, J. M. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00256-4 · Cited by 1,344
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SIRT6 Promotes DNA Repair Under Stress by Activating PARP1
Mao, Z., Hine, C., Tian, X., Van Meter, M., Au, M., Vaidya, A., Seluanov, A., & Gorbunova, V. (2011) · Science · doi:10.1126/science.1202723 · Cited by 867
Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH
Zhang, G., Li, J., Purkayastha, S., Tang, Y., Zhang, H., Yin, Y., Li, B., Liu, G., & Cai, D. (2013) · Nature · doi:10.1038/nature12143 · Cited by 834
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 820
The 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 842
Linking functional decline of telomeres, mitochondria and stem cells during ageing
Sahin, E., & DePinho, R. A. (2010) · Nature · doi:10.1038/nature08982 · Cited by 759
Stability and kinetics of G-quadruplex structures
Lane, A. N., Chaires, J. B., Gray, R. D., & Trent, J. O. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn517 · Cited by 736
Therapeutic application of histone deacetylase inhibitors for central nervous system disorders
Kazantsev, A. G., & Thompson, L. M. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2681 · Cited by 727
SIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine
Jiang, H., Khan, S., Wang, Y., Charron, G., He, B., Sebastian, C., Du, J., Kim, R., Ge, E., Mostoslavsky, R., et al. (2013) · Nature · doi:10.1038/nature12038 · Cited by 697
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
Sirtuin regulation of mitochondria: energy production, apoptosis, and signaling
Verdin, E., Hirschey, M. D., Finley, L. W. S., & Haigis, M. C. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.07.003 · Cited by 661
The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism
Sebastián, C., Zwaans, B. M. M., Silberman, D. M., Gymrek, M., Goren, A., Zhong, L., Ram, O., Truelove, J., Guimaraes, A. R., Toiber, D., et al. (2012) · Cell · doi:10.1016/j.cell.2012.10.047 · Cited by 660
Feldman, J. L., Baeza, J., & Denu, J. M. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.c113.511261 · Cited by 637
“However, several prior studies indicated that SIRT6 acted through deacetylation of histonemarksH3K9Ac (14) and H3K56Ac (15), which modulated HIF1- -dependent (16), NF- B-dependent (17), and c-Myc-dependent (3) pathways.”
BackgroundRegulation of SIRT1 in cellular functions: Role of polyphenols
Chung, S., Yao, H., Caito, S. W., Hwang, J., Arunachalam, G., & Rahman, I. (2010) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2010.05.003 · Cited by 664
Epigenetic 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
SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation
Barber, M. F., Michishita-Kioi, E., Xi, Y., Tasselli, L., Kioi, M., Moqtaderi, Z., Tennen, R. I., Paredes, S., Young, N. L., Chen, K., et al. (2012) · Nature · doi:10.1038/nature11043 · Cited by 635
Self-citationShah, P. P., Donahue, G., Otte, G. L., Capell, B. C., Nelson, D. M., Cao, K., Aggarwala, V., Cruickshanks, H. A., Rai, T. S., McBryan, T., et al. (2013) · Genes & Development · doi:10.1101/gad.223834.113 · Cited by 550
Lysosome-mediated processing of chromatin in senescence
Ivanov, A., Pawlikowski, J., Manoharan, I., van Tuyn, J., Nelson, D. M., Rai, T. S., Shah, P. P., Hewitt, G., Korolchuk, V. I., Passos, J. F., et al. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201212110 · Cited by 539
Purification of Proteins Associated with Specific Genomic Loci
Déjardin, J., & Kingston, R. E. (2009) · Cell · doi:10.1016/j.cell.2008.11.045 · Cited by 545
Brozovich, F. V., Nicholson, C., Degen, C. V., Gao, Y. Z., Aggarwal, M., & Morgan, K. G. (2016) · Pharmacological Reviews · doi:10.1124/pr.115.010652 · Cited by 568
Aging, Rejuvenation, and Epigenetic Reprogramming: Resetting the Aging Clock
Rando, T. A., & Chang, H. Y. (2012) · Cell · doi:10.1016/j.cell.2012.01.003 · Cited by 520
Self-citationInterplay between Metabolism and Epigenetics: A Nuclear Adaptation to Environmental Changes
Etchegaray, J., & Mostoslavsky, R. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.05.029 · Cited by 546
Booth, L. N., & Brunet, A. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.05.013 · Cited by 499
(2010) · doi:10.1016/j.cmet.2010.06.009 · Cited by 512
Redox regulation of SIRT1 in inflammation and cellular senescence
Hwang, J.-W., Yao, H., Caito, S., Sundar, I. K., & Rahman, I. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.03.015 · Cited by 503
The multifaceted functions of sirtuins in cancer
Chalkiadaki, A., & Guarente, L. (2015) · Nature reviews. Cancer · doi:10.1038/nrc3985 · Cited by 513
SIRT1 in Neurodevelopment and Brain Senescence
Herskovits, A. Z., & Guarente, L. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.028 · Cited by 504
The sirtuin SIRT6 blocks IGF-Akt signaling and development of cardiac hypertrophy by targeting c-Jun
Sundaresan, N. R., Vasudevan, P., Zhong, L., Kim, G. H., Samant, S. A., Parekh, V., Pillai, V. B., Veeranna, R. P., Gupta, M., Jeevanandam, V., et al. (2012) · Nature Medicine · doi:10.1038/nm.2961 · Cited by 484
Sirtuins, a promising target in slowing down the ageing process
Grabowska, W., Sikora, E., & Bielak-Zmijewska, A. (2017) · Biogerontology · doi:10.1007/s10522-017-9685-9 · Cited by 470
From Ancient Pathways to Aging Cells—Connecting Metabolism and Cellular Senescence
Wiley, C. D., & Campisi, J. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.010 · Cited by 440
Van Meter, M., Kashyap, M., Rezazadeh, S., Geneva, A. J., Morello, T. D., Seluanov, A., & Gorbunova, V. (2014) · Nature Communications · doi:10.1038/ncomms6011 · Cited by 456
Protective effects of sirtuins in cardiovascular diseases: from bench to bedside
Winnik, S., Auwerx, J., Sinclair, D. A., & Matter, C. M. (2015) · European Heart Journal · doi:10.1093/eurheartj/ehv290 · Cited by 422
Sirtuin signaling in cellular senescence and aging
Lee, S.-H., Lee, J.-H., Lee, H., & Min, K. (2019) · BMB Reports · doi:10.5483/bmbrep.2019.52.1.290 · Cited by 449
Targeting Sirtuin 1 to Improve Metabolism: All You Need Is NAD+?
Cantó, C., & Auwerx, J. (2012) · Pharmacological Reviews · doi:10.1124/pr.110.003905 · Cited by 433
Sirtuins — novel therapeutic targets to treat age-associated diseases
Lavu, S., Boss, O., Elliott, P. J., & Lambert, P. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2665 · Cited by 427
Psychological and metabolic stress: A recipe for accelerated cellular aging?
Epel, E. S. (2009) · HORMONES · doi:10.14310/horm.2002.1217 · Cited by 424
Reduced histone biosynthesis and chromatin changes arising from a damage signal at telomeres
O'Sullivan, R. J., Kubicek, S., Schreiber, S. L., & Karlseder, J. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1897 · Cited by 416
The nexus of chromatin regulation and intermediary metabolism
Gut, P., & Verdin, E. M. (2013) · Nature · doi:10.1038/nature12752 · Cited by 431
Chemical mechanisms of histone lysine and arginine modifications
Smith, B. C., & Denu, J. M. (2009) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2008.06.005 · Cited by 390
SIRT1 and SIRT6 Signaling Pathways in Cardiovascular Disease Protection
D’Onofrio, N., Servillo, L., & Balestrieri, M. L. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7178 · Cited by 396
Lopez-Rubio, J.-J., Mâncio-Silva, L., & Scherf, A. (2009) · Cell Host & Microbe · doi:10.1016/j.chom.2008.12.012 · Cited by 389
Nuclear DNA damage signalling to mitochondria in ageing
Fang, E. F., Scheibye-Knudsen, M., Chua, K. F., Mattson, M. P., Croteau, D. L., & Bohr, V. A. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.14 · Cited by 387
Self-citationCell cycle-dependent deacetylation of telomeric histone H3 lysine K56 by human SIRT6
Michishita, E., McCord, R. A., Boxer, L. D., Barber, M. F., Hong, T., Gozani, O., & Chua, K. F. (2009) · Cell Cycle · doi:10.4161/cc.8.16.9367 · Cited by 384
Self-citationAre sirtuins viable targets for improving healthspan and lifespan?
Baur, J. A., Ungvari, Z. I., Minor, R. K., Couteur, D. G. L., & de Cabo, R. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3738 · Cited by 393
SIRT6 is responsible for more efficient DNA double-strand break repair in long-lived species
Tian, X., Firsanov, D., Zhang, Z., Cheng, Y., Luo, L., Tombline, G., Tan, R., Simon, M., Henderson, S., Steffan, J., et al. (2019) · Cell · doi:10.1016/j.cell.2019.03.043 · Cited by 353
Seven sirtuins for seven deadly diseases ofaging
Morris, B. J. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.10.525 · Cited by 386
Lysine Acetylation Goes Global: From Epigenetics to Metabolism and Therapeutics
Ali, I., Conrad, R. J., Verdin, E. M., & Ott, M. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00181 · Cited by 375
Mitochondrial function in hypoxic ischemic injury and influence of aging
Ham, P. B., & Raju, R. P. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.06.006 · Cited by 374
Chromatin and beyond: the multitasking roles for SIRT6
Kugel, S., & Mostoslavsky, R. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2013.12.002 · Cited by 374
Sirt6 deficiency exacerbates podocyte injury and proteinuria through targeting Notch signaling
Liu, M., Liang, K., Zhen, J., Zhou, M., Wang, X., Wang, Z., Wei, X., Zhang, Y., Sun, Y., Zhou, Z., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00498-4 · Cited by 343
Screen for DNA‐damage‐responsive histone modifications identifies H3K9Ac and H3K56Ac in human cells
Tjeertes, J. V., Miller, K. M., & Jackson, S. P. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.119 · Cited by 347
Sirtuins mediate mammalian metabolic responses to nutrient availability
Chalkiadaki, A., & Guarente, L. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.225 · Cited by 344
SIRT6 safeguards human mesenchymal stem cells from oxidative stress by coactivating NRF2
Pan, H., Guan, D., Liu, X., Li, J., Wang, L., Wu, J., Zhou, J., Zhang, W., Ren, R., Zhang, W., et al. (2016) · Cell Research · doi:10.1038/cr.2016.4 · Cited by 335
SIRT4 is a lysine deacylase that controls leucine metabolism and insulin secretion
Anderson, K. A., Huynh, F. K., Fisher-Wellman, K., Stuart, J. D., Peterson, B. S., Douros, J. D., Wagner, G. R., Thompson, J. W., Madsen, A. S., Green, M. F., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.03.003 · Cited by 326
“SIRT6 is a highly specific lysine deacetylase (Michishita et al., 2008; Mostoslavsky et al., 2006), as well as a long-chain deacylase (Jiang et al.”
BackgroundMinagawa, S., Araya, J., Numata, T., Nojiri, S., Hara, H., Yumino, Y., Kawaishi, M., Odaka, M., Morikawa, T., Nishimura, S. L., et al. (2011) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00097.2010 · Cited by 323
Effects of Oxidative Stress on Mesenchymal Stem Cell Biology
Denu, R. A., & Hematti, P. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/2989076 · Cited by 338
The Dual Role of Sirtuins in Cancer
Bosch‐Presegué, L., & Vaquero, A. (2011) · Genes & Cancer · doi:10.1177/1947601911417862 · Cited by 337
Structure and Biochemical Functions of SIRT6
Pan, P. W., Feldman, J. L., Devries, M., Dong, A., Edwards, A. M., & Denu, J. M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.218990 · Cited by 312
SIRT6 protects against pathological damage caused by diet‐induced obesity
Kanfi, Y., Peshti, V., Gil, R., Naiman, S., Nahum, L., Levin, E., Kronfeld‐Schor, N., & Cohen, H. Y. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2009.00544.x · Cited by 311
RETRACTED: Human SIRT6 Promotes DNA End Resection Through CtIP Deacetylation
Kaidi, A., Weinert, B. T., Choudhary, C., & Jackson, S. P. (2010) · Science · doi:10.1126/science.1192049 · Cited by 366
RetractedRole of Sirtuin1-p53 regulatory axis in aging, cancer and cellular reprogramming
Ong, A. L. C., & Ramasamy, T. S. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.02.004 · Cited by 305
The Deacetylase Sirt6 Activates the Acetyltransferase GCN5 and Suppresses Hepatic Gluconeogenesis
Dominy, J. E., Lee, Y., Jedrychowski, M. P., Chim, H., Jurczak, M. J., Camporez, J. P., Ruan, H., Feldman, J., Pierce, K. A., Mostoslavsky, R., et al. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.09.030 · Cited by 303
Tatone, C., Emidio, G. D., Barbonetti, A., Carta, G., Luciano, A. M., Falone, S., & Amicarelli, F. (2018) · Human Reproduction Update · doi:10.1093/humupd/dmy003 · Cited by 296
The role of oxidative stress in ovarian aging: a review
Yan, F., Zhao, Q., Li, Y., Zheng, Z., Kong, X., Shu, C., Liu, Y., & Shi, Y. (2022) · Journal of Ovarian Research · doi:10.1186/s13048-022-01032-x · Cited by 324
Epigenetic principles and mechanisms underlying nervous system functions in health and disease
Mehler, M. F. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2008.10.001 · Cited by 300
Partitioning Circadian Transcription by SIRT6 Leads to Segregated Control of Cellular Metabolism
Masri, S., Rigor, P., Cervantes, M., Ceglia, N., Sebastian, C., Xiao, C., Roqueta-Rivera, M., Deng, C., Osborne, T. F., Mostoslavsky, R., et al. (2014) · Cell · doi:10.1016/j.cell.2014.06.050 · Cited by 292
Tonkin, C. J., Carret, C., Duraisingh, M. T., Voss, T. S., Ralph, S. A., Hommel, M., Duffy, M. F., Mâncio-Silva, L., Scherf, A., Ivens, A. C., et al. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000084 · Cited by 304
The Beneficial Roles of SIRT1 in Neuroinflammation-Related Diseases
Jiao, F., & Gong, Z. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/6782872 · Cited by 294
Mesenchymal Stem/Stromal Cell Senescence: Hallmarks, Mechanisms, and Combating Strategies
Weng, Z., Wang, Y., Ouchi, T., Liu, H., Qiao, X., Wu, C., Zhao, Z., Li, L., & Li, B. (2022) · Stem Cells Translational Medicine · doi:10.1093/stcltm/szac004 · Cited by 303
Van Gool, F., Gallí, M., Gueydan, C., Kruys, V., Prevot, P.-P., Bedalov, A., Mostoslavsky, R., Alt, F. W., De Smedt, T., & Leo, O. (2009) · Nature Medicine · doi:10.1038/nm.1906 · Cited by 285
Nakagawa, T., & Guarente, L. (2011) · Journal of Cell Science · doi:10.1242/jcs.081067 · Cited by 292
Sirtuins and Type 2 Diabetes: Role in Inflammation, Oxidative Stress, and Mitochondrial Function
Kitada, M., Ogura, Y., Monno, I., & Koya, D. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00187 · Cited by 298
DNA damage response and metabolic disease
Shimizu, I., Yoshida, Y., Suda, M., & Minamino, T. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.10.008 · Cited by 286
Sirtuins: guardians of mammalian healthspan
Giblin, W., Skinner, M. E., & Lombard, D. B. (2014) · Trends in Genetics · doi:10.1016/j.tig.2014.04.007 · Cited by 286
Energy metabolism in adult neural stem cell fate
Rafalski, V. A., & Brunet, A. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.10.007 · Cited by 294
Sirtuins in Epigenetic Regulation
Jing, H., & Lin, H. (2015) · Chemical Reviews · doi:10.1021/cr500457h · Cited by 276
Functions of the sirtuin deacylase SIRT5 in normal physiology and pathobiology
Kumar, S., & Lombard, D. B. (2018) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2018.1458071 · Cited by 273
SIRT6: Novel Mechanisms and Links to Aging and Disease
Tasselli, L., Zheng, W., & Chua, K. F. (2016) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2016.10.002 · Cited by 274
Self-citationTERRA: telomeric repeat‐containing RNA
Luke, B., & Lingner, J. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.166 · Cited by 266
NF‐κB signalling pathways in nucleus pulposus cell function and intervertebral disc degeneration
Zhang, G., Liu, M., Chen, H., Wu, Z., Gao, Y., Ma, Z., He, X., & Kang, X. (2021) · Cell Proliferation · doi:10.1111/cpr.13057 · Cited by 265
Oxidative Stress in Pulmonary Fibrosis
Otoupalova, E., Smith, S., Cheng, G., & Thannickal, V. J. (2020) · Comprehensive physiology · doi:10.1002/cphy.c190017 · Cited by 312
Regulation of Akt Signaling by Sirtuins
Pillai, V. B., Sundaresan, N. R., & Gupta, M. P. (2014) · Circulation Research · doi:10.1161/circresaha.113.300536 · Cited by 262
Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders
Jęśko, H. M., Wencel, P. L., Strosznajder, R. P., & Strosznajder, J. B. (2016) · Neurochemical Research · doi:10.1007/s11064-016-2110-y · Cited by 264
Levy, D., Kuo, A. J., Chang, Y., Schaefer, U., Kitson, C., Cheung, P., Espejo, A. B., Zee, B. M., Liu, C. L., Tangsombatvisit, S., et al. (2010) · Nature Immunology · doi:10.1038/ni.1968 · Cited by 266
Self-citationSirtuins, Cell Senescence, and Vascular Aging
Kida, Y., & Goligorsky, M. S. (2015) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2015.11.022 · Cited by 258
The sirtuin SIRT6 deacetylates H3 K56Ac in vivo to promote genomic stability
Yang, B., Zwaans, B. M. M., Eckersdorff, M., & Lombard, D. B. (2009) · Cell Cycle · doi:10.4161/cc.8.16.9329 · Cited by 254
SIRT6 Protects Smooth Muscle Cells From Senescence and Reduces Atherosclerosis
Grootaert, M. O. J., Finigan, A. J., Figg, N. L., Uryga, A., & Bennett, M. R. (2020) · Circulation Research · doi:10.1161/circresaha.120.318353 · Cited by 252
Metadata
- Authors
- Michishita, E., McCord, R. A., Berber, E., Kioi, M., Padilla-Nash, H., Damian, M., Cheung, P., Kusumoto, R., Kawahara, T. L. A., Barrett, J. C., Chang, H. Y., Bohr, V. A., Ried, T., Gozani, O., & Chua, K. F.
- Affiliations
- Stanford Medicine (US)
- VA Palo Alto Health Care System (US)
- Department of Biological Sciences (RU)
- National Institutes of Health (US)
- Corresponding author
- Chua, Katrin F.
- ORCID
- Venue
- Nature
- Published
- 2008-03
- Volume
- 452
- Issue
- 7186
- Pages
- 492-496
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2646112
- OpenAlex
- W2029969982
- Semantic Scholar
- e93e298451cb0d965e8933da9a3ab04e44f65ff0
- Cited by
- 1,111
- References
- 32
- Citations by year
- 2026: 35 · 2025: 35 · 2024: 45 · 2023: 59 · 2022: 57 · 2021: 68 · 2020: 75 · 2019: 64 · 2018: 75 · 2017: 63 · 2016: 83 · 2015: 68 · 2014: 62 · 2013: 94 · 2012: 57
- FWCI
- 23.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute on Aging (R01AG028867, K08AG028961)
- National Institute of General Medical Sciences (R01GM079641)
- 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 › Molecular Biology › Nuclear Structure and Function
- Keywords
- SIRT6, telomeric chromatin, telomere maintenance, premature aging, Werner syndrome, WRN, cellular senescence, chromatin silencing, telomere dysfunction, NAD+-dependent deacetylation
- MeSH terms
- Werner Syndrome Helicase, Acetylation, Cell Line, Chromatin, DNA Replication, Exodeoxyribonucleases, Fibroblasts, Histone Deacetylases, Histones, Humans, Lysine, Phenotype, Protein Binding, Werner Syndrome, Telomere, Cellular Senescence, Telomerase, Sirtuins, RecQ Helicases
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