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Telomere Dysfunction Induces Sirtuin Repression that Drives Telomere-Dependent Disease
Open accessAbstract
Telomere shortening is associated with stem cell decline, fibrotic disorders, and premature aging through mechanisms that are incompletely understood. Here, we show that telomere shortening in livers of telomerase knockout mice leads to a p53-dependent repression of all seven sirtuins. P53 regulates non-mitochondrial sirtuins (Sirt1, 2, 6, and 7) post-transcriptionally through microRNAs (miR-34a, 26a, and 145), while the mitochondrial sirtuins (Sirt3, 4, and 5) are regulated in a peroxisome proliferator-activated receptor gamma co-activator 1 alpha-/beta-dependent manner at the transcriptional level. Administration of the NAD(+) precursor nicotinamide mononucleotide maintains telomere length, dampens the DNA damage response and p53, improves mitochondrial function, and, functionally, rescues liver fibrosis in a partially Sirt1-dependent manner. These studies establish sirtuins as downstream targets of dysfunctional telomeres and suggest that increasing Sirt1 activity alone or in combination with other sirtuins stabilizes telomeres and mitigates telomere-dependent disorders.
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“NMN promoted telomere lengthening in aged mice [36], pre-aging mice and humans [37•].”
From NAD+ Precursors Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR): Potential Dietary Contribution to Health (2023) · cites this paper as [36]
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“Treatment with NMN (dissolved in 5-mM drinking water for 8 weeks) promoted telomere lengthening in generation 4 (G4) mice, dampened the DNA damage response and p53, functionally rescued liver fibrosis, and improved the mitochondrial biogenesis and function in a partially SIRT1-dependent manner [36].”
From NAD+ Precursors Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR): Potential Dietary Contribution to Health (2023) · cites this paper as [36]
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“The increased NAD+ levels in the liver tissue of NMN-treated G4 mice reversed the hyperacetylation of several sirtuin targets indicating the reinforcement of sirtuin activity [36].”
From NAD+ Precursors Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR): Potential Dietary Contribution to Health (2023) · cites this paper as [36]
In the citing paper
“In addition, the concerted action of sirtuins has been found to stabilize telomers and alleviate telomere-associated disorders (Amano et al. 2019).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Amano et al. 2019
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Cites
NIH Image to ImageJ: 25 years of image analysis
Schneider, C. A., Rasband, W. S., & Eliceiri, K. W. (2012) · Nature Methods · doi:10.1038/nmeth.2089 · Cited by 64,638
limma powers differential expression analyses for RNA-sequencing and microarray studies
Ritchie, M. E., Phipson, B., Wu, D., Hu, Y., Law, C. W., Shi, W., & Smyth, G. K. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv007 · Cited by 40,458
Predicting effective microRNA target sites in mammalian mRNAs
Agarwal, V., Bell, G. W., Nam, J.-W., & Bartel, D. P. (2015) · eLife · doi:10.7554/elife.05005 · Cited by 7,318
Lagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H., Lerin, C., Daussin, F., Messadeq, N., Milne, J., Lambert, P., Elliott, P., et al. (2006) · Cell · doi:10.1016/j.cell.2006.11.013 · Cited by 4,057
MicroRNA targets in Drosophila
Enright, A. J., John, B., Gaul, U., Tuschl, T., Sander, C., & Marks, D. S. (2003) · Genome Biology · doi:10.1186/gb-2003-5-1-r1 · Cited by 3,597
Fast and effective prediction of microRNA/target duplexes
REHMSMEIER, M., STEFFEN, P., HÖCHSMANN, M., & GIEGERICH, R. (2004) · RNA · doi:10.1261/rna.5248604 · Cited by 2,560
Miranda, K. C., Huynh, T., Tay, Y., Ang, Y.-S., Tam, W.-L., Thomson, A. M., Lim, B., & Rigoutsos, I. (2006) · Cell · doi:10.1016/j.cell.2006.07.031 · Cited by 2,063
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
Dweep, H., Sticht, C., Pandey, P., & Gretz, N. (2011) · Journal of Biomedical Informatics · doi:10.1016/j.jbi.2011.05.002 · Cited by 1,707
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
miR-34a repression of SIRT1 regulates apoptosis
Yamakuchi, M., Ferlito, M., & Lowenstein, C. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801613105 · Cited by 1,362
Yoshino, J., Mills, K. F., Yoon, M. J., & Imai, S.-I. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.014 · Cited by 1,340
Position effect at S. cerevisiae telomeres: Reversible repression of Pol II transcription
Gottschling, D. E., Aparicio, O. M., Billington, B. L., & Zakian, V. A. (1990) · Cell · doi:10.1016/0092-8674(90)90141-z · Cited by 1,325
Telomere dysfunction induces metabolic and mitochondrial compromise
Sahin, E., Colla, S., Liesa, M., Moslehi, J., Müller, F. L., Guo, M., Cooper, M., Kotton, D., Fabian, A. J., Walkey, C., et al. (2011) · Nature · doi:10.1038/nature09787 · Cited by 1,319
Self-citationCantó, C., Houtkooper, R. H., Pirinen, E., Youn, D. Y., Oosterveer, M. H., Cen, Y., Fernandez-Marcos, P. J., Yamamoto, H., Andreux, P. A., Cettour-Rose, P., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.022 · Cited by 1,238
Mouchiroud, L., Houtkooper, R. H., Moullan, N., Katsyuba, E., Ryu, D., Cantó, C., Mottis, A., Jo, Y.-S., Viswanathan, M., Schoonjans, K., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.016 · Cited by 1,210
DIANA-microT web server v5.0: service integration into miRNA functional analysis workflows
Paraskevopoulou, M. D., Georgakilas, G. K., Kostoulas, N., Vlachos, I. S., Vergoulis, T., Reczko, M., Filippidis, C., Dalamagas, T., & Hatzigeorgiou, A. G. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt393 · Cited by 1,171
SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin
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., et al. (2008) · Nature · doi:10.1038/nature06736 · Cited by 1,111
Armanios, M., & Blackburn, E. H. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3246 · Cited by 982
Chin, L., Artandi, S. E., Shen, Q., Tam, A., Lee, S.-L., Gottlieb, G. J., Greider, C. W., & DePinho, R. A. (1999) · Cell · doi:10.1016/s0092-8674(00)80762-x · Cited by 979
Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., Redpath, P., Migaud, M. E., Apte, R. S., Uchida, K., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.013 · Cited by 930
Mild hyperoxia shortens telomeres and inhibits proliferation of fibroblasts: a model for senescence?
von Zglinicki, T., Saretzki, G., Döcke, W., & Lotze, C. (1995) · Experimental Cell Research · doi:10.1006/excr.1995.1305 · Cited by 856
SIRT1 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
Self-citationCalado, R. T., & Young, N. S. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0903373 · Cited by 814
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
Self-citationSir2 links chromatin silencing, metabolism, and agingPreprint
Guarente, L. (2000) · Genes & Development · doi:10.1101/gad.14.9.1021 · Cited by 718
Kong, X., Wang, R., Xue, Y., Liu, X., Zhang, H., Chen, Y., Fang, F., & Chang, Y. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011707 · Cited by 718
Vakhrusheva, O., Smolka, C., Gajawada, P., Sawa Kostin, D., Boettger, T., Kubin, T., Braun, T. W., & Bober, E. (2008) · Circulation Research · doi:10.1161/circresaha.107.164558 · Cited by 646
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
Inhibition of Experimental Liver Cirrhosis in Mice by Telomerase Gene Delivery
Rudolph, K. L., Chang, S., Millard, M., Schreiber-Agus, N., & DePinho, R. A. (2000) · Science · doi:10.1126/science.287.5456.1253 · Cited by 424
Tarragó, M. G., Chini, C. C. S., Kanamori, K. S., Warner, G. M., Caride, A., de Oliveira, G. C., Rud, M., Samani, A., Hein, K. Z., Huang, R., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.03.016 · Cited by 384
A high-fat diet and NAD(+) activate Sirt1 to rescue premature aging in Cockayne syndrome
Scheibye-Knudsen, M., Mitchell, S. J., Fang, E. F., Iyama, T., Ward, T., Wang, J., Dunn, C. A., Singh, N., Veith, S., Hasan-Olive, M. M., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.10.005 · Cited by 352
Castro, R. E., Ferreira, D. M. S., Afonso, M. B., Borralho, P. M., Machado, M. V., Cortez‐Pinto, H., & Rodrigues, C. M. P. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.08.008 · Cited by 351
Mills, K. D., Sinclair, D. A., & Guarente, L. (1999) · Cell · doi:10.1016/s0092-8674(00)80772-2 · Cited by 334
Self-citationThe Role of PARP-1 and PARP-2 Enzymes in Metabolic Regulation and Disease
Bai, P., & Cantó, C. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.06.016 · Cited by 312
SIRT1 contributes to telomere maintenance and augments global homologous recombination
Palacios, J., Herranz, D., Bonis, M. L. D., Velasco, S., Serrano, M., & Blasco, M. A. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.201005160 · Cited by 263
Savage, S. A., & Alter, B. P. (2009) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2009.01.003 · Cited by 262
Experimental models of hepatocellular carcinoma
Newell, P. H., Villanueva, A., Friedman, S. L., Koike, K., & Llovet, J. M. (2008) · Journal of Hepatology · doi:10.1016/j.jhep.2008.01.008 · Cited by 233
Intact p53-Dependent Responses in miR-34–Deficient Mice
Concepcion, C. P., Han, Y.-C., Mu, P., Bonetti, C., Yao, E., D'Andrea, A., Vidigal, J. A., Maughan, W. P., Ogrodowski, P., & Ventura, A. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002797 · Cited by 197
Telomerase gene mutations are associated with cirrhosis formation
Hartmann, D., Srivastava, U., Thaler, M., Kleinhans, K. N., N'Kontchou, G., Scheffold, A., Bauer, K., Kratzer, R. F., Kloos, N., Katz, S.-F., et al. (2011) · Hepatology · doi:10.1002/hep.24217 · Cited by 173
Chromatin regulation and genome maintenance by mammalian SIRT6
Tennen, R. I., & Chua, K. F. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.07.009 · Cited by 167
Identification of Novel and Known miRNAs in Deep‐Sequencing Data with miRDeep2
Mackowiak, S. D. (2011) · Current Protocols in Bioinformatics · doi:10.1002/0471250953.bi1210s36 · Cited by 161
PARP1 Is a TRF2-associated Poly(ADP-Ribose)Polymerase and Protects Eroded Telomeres
Gomez, M., Wu, J., Schreiber, V., Dunlap, J. R., Dantzer, F., Wang, Y., & Liu, Y. (2006) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-07-0672 · Cited by 125
Nicotinamide adenine dinucleotide biosynthesis promotes liver regeneration
Mukherjee, S., Chellappa, K., Moffitt, A. B., Ndungu, J., Dellinger, R. W., Davis, J. G., Agarwal, B., & Baur, J. A. (2016) · Hepatology · doi:10.1002/hep.28912 · Cited by 108
Self-citationMaicher, A., Kastner, L., Dees, M., & Luke, B. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks358 · Cited by 107
Long-range silencing and position effects at telomeres and centromeres: parallels and differences
Perrod, S., & Gasser, S. M. (2003) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-003-3246-x · Cited by 100
Rapid regulation of telomere length is mediated by poly(ADP-ribose) polymerase-1
Beneke, S., Cohausz, O., Malanga, M., Boukamp, P., Althaus, F., & Bürkle, A. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn615 · Cited by 91
Telomere shortening and metabolic compromise underlie dystrophic cardiomyopathy
Chang, A. C. Y., Ong, S.-G., LaGory, E. L., Kraft, P. E., Giaccia, A. J., Wu, J. C., & Blau, H. M. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1615340113 · Cited by 81
PRDX1 and MTH1 cooperate to prevent ROS-mediated inhibition of telomerasePreprint
Ahmed, W., & Lingner, J. (2018) · Genes & Development · doi:10.1101/gad.313460.118 · Cited by 78
Yang, T.-L. B., Chen, Q., Deng, J. T., Jagannathan, G., Tobias, J. W., Schultz, D., Wang, S., Lengner, C. J., Rustgi, A. K., Lynch, J. P., et al. (2017) · Nature Communications · doi:10.1038/ncomms14766 · Cited by 31
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Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
Jomova, K., Raptova, R., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., & Valko, M. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03562-9 · Cited by 2,638
Modulation of cellular processes by histone and non-histone protein acetylation
Shvedunova, M., & Akhtar, A. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00441-y · Cited by 1,007
NAD+ in Brain Aging and Neurodegenerative Disorders
Lautrup, S., Sinclair, D. A., Mattson, M. P., & Fang, E. F. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.09.001 · Cited by 790
Self-citationTelomeres: history, health, and hallmarks of aging
Chakravarti, D., LaBella, K. A., & DePinho, R. A. (2021) · Cell · doi:10.1016/j.cell.2020.12.028 · Cited by 637
NAD+ 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
Metadata
- Authors
- Amano, H., Chaudhury, A., Rodriguez-Aguayo, C., Lu, L., Akhanov, V., Catic, A., Popov, Y. V., Verdin, E., Johnson, H., Stossi, F., Sinclair, D. A., Nakamaru-Ogiso, E., Lopez-Berestein, G., Chang, J. T., Neilson, J. R., Meeker, A., Finegold, M., Baur, J. A., & Sahin, E.
- Affiliations
- Baylor College of Medicine (US)
- Philips (United States) (US)
- Beth Israel Deaconess Medical Center (US)
- Gladstone Institutes (US)
- Harvard University (US)
- The University of Texas Health Science Center at Houston (US)
- Johns Hopkins University (US)
- University of Pennsylvania (US)
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 29
- Issue
- 6
- Pages
- 1274-1290.e9
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC6657508
- OpenAlex
- W2927492624
- Cited by
- 182
- References
- 51
- Citations by year
- 2026: 13 · 2025: 31 · 2024: 27 · 2023: 34 · 2022: 26 · 2021: 22 · 2020: 20 · 2019: 9
- FWCI
- 10.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (AG043483, DK098656, CA125123, DK56338, FP00000019, R01DK115454)
- National Institute on Aging (R01AG047924)
- National Cancer Institute (CA190467)
- American Cancer Society (RSG-15-088-01RMC)
- Glenn Foundation for Medical Research (R01 DK100263, AG043483, R21 DE027490, R01 AG019719, DK098656, R37 AG028730)
- Cancer Prevention and Research Institute of Texas (RP170719, RP150578)
- 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
- telomere shortening, sirtuins, p53, liver fibrosis, microRNA, miR-34a, miR-26a, miR-145, SIRT1, nicotinamide mononucleotide, NAD+ precursors, DNA damage response, mitochondrial function, premature aging
- MeSH terms
- Animals, Cells, Cultured, Embryo, Mammalian, Female, Humans, Liver, Liver Cirrhosis, Male, Mice, Inbred C57BL, Mitochondria, Liver, Nicotinamide Mononucleotide, Down-Regulation, Gene Expression Regulation, Enzymologic, Mice, Knockout, Telomerase, Sirtuins, Mice, Sirtuin 1, HEK293 Cells, Telomere Homeostasis, Telomere Shortening
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