The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
Mammalian Sirtuins: Biological Insights and Disease Relevance
Open accessAbstract
Aging is accompanied by a decline in the healthy function of multiple organ systems, leading to increased incidence and mortality from diseases such as type II diabetes mellitus, neurodegenerative diseases, cancer, and cardiovascular disease. Historically, researchers have focused on investigating individual pathways in isolated organs as a strategy to identify the root cause of a disease, with hopes of designing better drugs. Studies of aging in yeast led to the discovery of a family of conserved enzymes known as the sirtuins, which affect multiple pathways that increase the life span and the overall health of organisms. Since the discovery of the first known mammalian sirtuin, SIRT1, 10 years ago, there have been major advances in our understanding of the enzymology of sirtuins, their regulation, and their ability to broadly improve mammalian physiology and health span. This review summarizes and discusses the advances of the past decade and the challenges that will confront the field in the coming years.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Proposed drivers of physiological aging include the accumulation of DNA damage, increased ROS production, telomere shortening, cellular senescence, and defects in nuclear envelope architecture (Bernardes de Jesus and Blasco, 2013;Guarente, 2008;Haigis and Sinclair, 2009;Kennedy and Lamming, 2016;Soultoukis and Partridge, 2016;Steffen and Dillin, 2016).”
From In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming. (2016) · cites this paper as Haigis and Sinclair, 2009
Experimental — accuracy not yet measuredIn the citing paper
“Sirtuins are NAD+‐dependent enzymes implicated in a range of physiological and pathophysiological conditions, including AS, diabetes mellitus, cancer, longevity, and neurodegeneration, through deacetylation of numerous substrates.42”
From Trimethylamine‐N‐Oxide Induces Vascular Inflammation by Activating the NLRP3 Inflammasome Through the SIRT3‐SOD2‐mtROS Signaling Pathway (2017) · cites this paper as [42]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
2 retracted
Visfatin: A Protein Secreted by Visceral Fat That Mimics the Effects of Insulin
Fukuhara, A., Matsuda, M., Nishizawa, M., Segawa, K., Tanaka, M., Kishimoto, K., Matsuki, Y., Murakami, M., Ichisaka, T., Murakami, H., et al. (2005) · Science · doi:10.1126/science.1097243 · Cited by 1,906
RetractedRETRACTED: Metabolic regulation of SIRT1 transcription via a HIC1:CtBP corepressor complex
Zhang, Q., Wang, S.-Y., Fleuriel, C., Leprince, D., Rocheleau, J. V., Piston, D. W., & Goodman, R. H. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610590104 · Cited by 171
RetractedCancer chemopreventive activity of resveratrol, a natural product derived from grapes
Jang, M., Cai, L., Udeani, G. O., Slowing, K. V., Thomas, C. F., Beecher, C. W. W., Fong, H. H. S., Farnsworth, N. R., Kinghorn, A. D., Mehta, R. G., et al. (1997) · Science · doi:10.1126/science.275.5297.218 · Cited by 4,935
Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
Donehower, L. A., Harvey, M., Slagle, B. L., McArthur, M. J., Montgomery, C. A., Butel, J. S., & Bradley, A. (1992) · Nature · doi:10.1038/356215a0 · Cited by 4,649
Resveratrol improves health and survival of mice on a high-calorie diet
Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., Prabhu, V. V., Allard, J. S., Lopez-Lluch, G., Lewis, K., et al. (2006) · Nature · doi:10.1038/nature05354 · Cited by 4,290
Self-citationLagouge, 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
Small 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
Self-citationTranscriptional 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
AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity
Cantó, C., Gerhart-Hines, Z., Feige, J. N., Lagouge, M., Noriega, L., Milne, J. C., Elliott, P. J., Puigserver, P., & Auwerx, J. (2009) · Nature · doi:10.1038/nature07813 · Cited by 3,300
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
Self-citation
Research works printed but not linked: 237
- 10.1016/S0092-8674(00)80493-6 · DOI · Paper page
- 10.1038/scientificamerican0306-48 · DOI
- 10.1016/j.tibs.2007.09.008 · DOI
- 10.1006/bbrc.1999.0897 · DOI
- 10.1101/gad.11.2.241 · DOI
- 10.1101/gad.11.2.255 · DOI
- 10.1126/science.1080418 · DOI
- 10.1186/gb-2004-5-5-224 · DOI
- 10.1038/35065638 · DOI · Paper page
- 10.1016/j.mad.2005.09.005 · DOI
- 10.1073/pnas.0404184101 · DOI · Paper page
- 10.1006/bbrc.2000.3000 · DOI · Paper page
- 10.1074/jbc.273.48.31788 · DOI
- 10.1016/S1097-2765(03)00038-8 · DOI
- 10.1073/pnas.250422697 · DOI
- 10.1006/bbrc.2000.3854 · DOI
- 10.1016/j.cell.2006.06.057 · DOI · Paper page
- 10.1016/S0092-8674(00)81671-2 · DOI
- 10.1016/S0955-0674(00)00202-7 · DOI
- 10.1021/bi011858j · DOI
- 10.1074/jbc.M407484200 · DOI
- 10.1021/bi049592e · DOI
- 10.2174/138161209787185797 · DOI
- 10.1016/j.chembiol.2008.09.009 · DOI
- 10.1146/annurev.biochem.74.082803.133500 · DOI · Paper page
- 10.1016/j.molcel.2004.12.032 · DOI
- 10.1021/bi034959l · DOI
- 10.1016/S1097-2765(04)00082-6 · DOI
- 10.1074/jbc.M804681200 · DOI
- 10.1128/MCB.24.3.1301-1312.2004 · DOI · Paper page
- 10.1016/S0092-8674(04)00416-7 · DOI · Paper page
- 10.1002/1521-4141(200211)32:11<3225::AID-IMMU3225>3.0.CO;2-L · DOI
- 10.1016/j.exger.2006.06.003 · DOI
- 10.1016/j.cell.2007.07.035 · DOI · Paper page
- 10.1074/jbc.M109.016469 · DOI
- 10.1007/s12013-008-9041-4 · DOI
- 10.1146/annurev.nutr.28.061807.155443 · DOI · Paper page
- 10.1126/science.1060698 · DOI · Paper page
- 10.1126/science.1171641 · DOI · Paper page
- 10.1096/fj.09-129148 · DOI
- 10.1126/science.1170803 · DOI · Paper page
- 10.1016/j.bbrc.2006.08.066 · DOI
- 10.2119/2006-00099.Lund · DOI
- 10.1016/j.cell.2005.03.035 · DOI
- 10.1074/jbc.M513741200 · DOI
- 10.1074/jbc.M208997200 · DOI
- 10.1042/BJ20070140 · DOI
- 10.1371/journal.pone.0000784 · DOI
- 10.1074/jbc.M609554200 · DOI
- 10.1016/S1097-2765(04)00094-2 · DOI
- 10.1083/jcb.200205057 · DOI
- 10.1073/pnas.0603968103 · DOI · Paper page
- 10.1042/BJ20080336 · DOI
- 10.1016/j.bbrc.2007.11.122 · DOI
- 10.1101/gad.1527307 · DOI
- 10.1074/jbc.M109.014928 · DOI
- 10.1016/j.mad.2005.03.019 · DOI
- 10.1111/j.1474-9726.2006.00236.x · DOI
- 10.1096/fj.03-1464fje · DOI
- 10.1038/35041700 · DOI
- 10.1126/science.1113611 · DOI
- 10.1371/journal.pgen.0010069 · DOI
- 10.1016/j.cell.2005.08.042 · DOI
- 10.1371/journal.pbio.0050261 · DOI · Paper page
- 10.1074/jbc.M111773200 · DOI
- 10.1016/S0531-5565(00)00084-X · DOI · Paper page
- 10.1016/j.mad.2004.01.006 · DOI
- 85. Sinclair DA, Howitz KT. 2006. Dietary Restriction, Hormesis, and Small Molecule Mimetics . Amsterdam/Boston: Elsevier. 660pp. · DOI
- 10.1126/science.1099196 · DOI · Paper page
- 10.1111/j.1474-9726.2007.00335.x · DOI · Paper page
- 10.1016/j.cmet.2008.08.014 · DOI
- 10.1073/pnas.0802917105 · DOI · Paper page
- 10.1016/j.cmet.2008.05.004 · DOI · Paper page
- 10.1128/MCB.23.1.38-54.2003 · DOI · Paper page
- 10.1038/ncb1468 · DOI
- 10.1126/science.1101731 · DOI
- 10.1016/j.cell.2005.08.011 · DOI
- 10.1161/CIRCRESAHA.108.193102 · DOI
- 10.4161/cc.8.5.7753 · DOI
- 10.1016/j.taap.2008.12.021 · DOI
- 10.1016/j.bbrc.2008.09.086 · DOI
- 10.1073/pnas.0801613105 · DOI
- 10.1083/jcb.200809167 · DOI
- 10.1128/MCB.26.1.28-38.2006 · DOI
- 10.1021/jm050100l · DOI
- 10.1186/1752-0509-3-31 · DOI · Paper page
- 10.1038/nrd2665 · DOI
- 10.1073/pnas.0403493101 · DOI · Paper page
- 10.1016/j.femsyr.2004.06.015 · DOI
- 10.1016/j.devcel.2005.09.017 · DOI
- 10.1016/j.mad.2007.07.007 · DOI
- 10.1074/jbc.M500655200 · DOI · Paper page
- 10.1177/1087057106294710 · DOI
- 122. Galonek H, Miller C, Israelian K, Ribish S, Lynch AV, et al. 2009. Enzymatic and cellular activity of small molecule activators of SIRT1 . Presented at NAD Metab. Signal., FASEB J. Conf., Carefree, Ariz.
- 10.1016/j.molcel.2008.09.011 · DOI
- 10.1016/j.cmet.2007.08.014 · DOI · Paper page
- 10.1038/onc.2009.147 · DOI
- 10.1016/j.molcel.2007.08.030 · DOI
- 10.1523/JNEUROSCI.3052-08.2008 · DOI
- 10.1038/nature06515 · DOI
- 10.1038/nature06500 · DOI
- 10.1371/journal.pone.0004020 · DOI
- 10.1016/S0092-8674(00)81410-5 · DOI · Paper page
- 10.1016/j.febslet.2007.11.034 · DOI · Paper page
- 10.1016/j.cmet.2009.02.006 · DOI · Paper page
- 10.1038/nature07349 · DOI · Paper page
- 10.1097/MOL.0b013e328328d0a4 · DOI · Paper page
- 10.1016/j.devcel.2008.04.012 · DOI
- 10.1038/sj.emboj.7601633 · DOI · Paper page
- 10.1152/ajpgi.90358.2008 · DOI · Paper page
- 10.1152/ajpgi.00575.2007 · DOI
- 10.1016/j.molcel.2007.07.032 · DOI
- 10.1073/pnas.0712145105 · DOI
- 10.1016/j.cmet.2005.07.001 · DOI
- 10.1038/nature02583 · DOI
- 10.1074/jbc.M607215200 · DOI
- 10.1146/annurev.genet.39.110304.095751 · DOI · Paper page
- 10.1073/pnas.222538099 · DOI
- 10.1128/MCB.01636-07 · DOI · Paper page
- 10.1073/pnas.0604392103 · DOI · Paper page
- 10.1016/j.jmb.2008.07.048 · DOI · Paper page
- 10.1073/pnas.0803790105 · DOI · Paper page
- 10.1002/pro.50 · DOI
- 10.1016/j.ygeno.2006.09.004 · DOI
- 10.1074/jbc.M705488200 · DOI · Paper page
- 10.1016/j.ymgme.2003.10.013 · DOI
- 10.1128/MCB.00426-08 · DOI
- 10.1016/j.ccr.2008.04.009 · DOI
- 10.1038/nrc2562 · DOI
- 10.1016/S0092-8674(01)00524-4 · DOI · Paper page
- 10.1016/S0092-8674(01)00527-X · DOI
- 10.1016/j.cell.2008.10.025 · DOI · Paper page
- 10.7150/ijbs.5.147 · DOI
- 10.1038/onc.2008.388 · DOI
- 10.1158/0008-5472.CAN-07-0085 · DOI
- 10.1038/sj.leu.2403910 · DOI
- 10.1002/biot.200700087 · DOI
- 10.1007/s00403-006-0725-6 · DOI
- 10.1016/j.ccr.2008.09.001 · DOI
- 10.1245/s10434-008-9940-z · DOI
- 10.1074/jbc.M702990200 · DOI
- 10.4161/cc.8.8.8245 · DOI
- 10.1016/j.bbrc.2003.08.029 · DOI
- 10.1038/nature07861 · DOI
- 10.1038/sj.onc.1209857 · DOI
- 10.1038/sj.bjc.6603384 · DOI
- 10.1038/sj.bjc.6600635 · DOI
- 10.1158/0008-5472.CAN-05-1923 · DOI
- 10.1038/onc.2008.436 · DOI
- 10.1016/S0092-8674(01)00524-4 · DOI · Paper page
- 10.1016/j.ccr.2008.03.004 · DOI
- 10.1073/pnas.1934713100 · DOI · Paper page
- 10.1038/sj.onc.1209049 · DOI
- 10.1016/j.yjmcc.2007.08.008 · DOI
- 10.1371/journal.pone.0001710 · DOI
- 10.1016/j.cell.2008.11.008 · DOI
- 10.1101/gad.435107 · DOI · Paper page
- 10.4161/cc.7.14.6267 · DOI
- 10.4161/cc.6.23.5026 · DOI
- 10.4161/cc.7.10.5883 · DOI
- 10.1093/ajcn/55.6.1250S · DOI
- 10.1038/nrd2060 · DOI · Paper page
- 10.1016/S0960-9822(00)00002-6 · DOI · Paper page
- 10.1038/ng0994-66 · DOI
- 10.1111/j.1474-9726.2006.00191.x · DOI
- 10.1016/S0092-8674(00)80773-4 · DOI · Paper page
- 10.1016/S0960-9822(99)80339-X · DOI
- 10.1128/MCB.21.16.5359-5373.2001 · DOI
- 10.1128/MCB.25.12.4903-4913.2005 · DOI
- 10.1016/j.molcel.2007.05.029 · DOI
- 10.1126/science.275.5297.218 · DOI · Paper page
- 10.1128/MCB.23.9.3173-3185.2003 · DOI
- 10.1016/j.bbrc.2009.06.113 · DOI
- 10.1158/0008-5472.CAN-05-3617 · DOI
- 10.4161/cc.6.21.4866 · DOI
- 10.1016/j.cell.2005.11.044 · DOI · Paper page
- 10.1002/jcb.21140 · DOI
- 10.1038/cdd.2008.122 · DOI
- 10.1161/01.CIR.0000140677.20606.0E · DOI
- 10.1001/jama.295.13.1539 · DOI · Paper page
- 10.1128/MMBR.67.3.376-399.2003 · DOI
- 10.2174/138161209787185742 · DOI
- 10.1093/cvr/cvn245 · DOI
- 10.1093/eurheartj/ehm149 · DOI
- 10.1152/ajpgi.00016.2009 · DOI
- 10.1128/MCB.00705-08 · DOI
- 10.1016/j.cmet.2008.06.011 · DOI · Paper page
- 10.1152/ajpheart.00235.2008 · DOI
- 10.1161/01.CIR.0000029925.18593.5C · DOI
- 10.1016/j.yjmcc.2006.10.018 · DOI
- Rush JW, 2007, Exp. Biol. Med., 232, 814, 10.3181/00379727-232-2320814 · DOI
- 10.1073/pnas.0704329104 · DOI · Paper page
- 10.1371/journal.pmed.0040076 · DOI · Paper page
- 10.1111/j.1474-9726.2009.00453.x · DOI
- 10.1093/cvr/cvn224 · DOI · Paper page
- 10.1161/CIRCRESAHA.107.152165 · DOI
- 10.1172/JCI23126 · DOI
- 10.1042/BST0340731 · DOI
- 10.1016/j.cell.2006.12.029 · DOI · Paper page
- 10.1016/S0006-291X(02)03020-6 · DOI
200 of 237 shown
Cited by
Sorted by citations
Autophagy and the Integrated Stress Response
Kroemer, G., Mariño, G., & Levine, B. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.023 · Cited by 3,506
Hypoxia-inducible factors and the response to hypoxic stress
Majmundar, A. J., Wong, W. J., & Simon, M. C. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.022 · Cited by 2,380
Rubinsztein, D. C., Mariño, G., & Kroemer, G. (2011) · Cell · doi:10.1016/j.cell.2011.07.030 · Cited by 2,107
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
Cantó, C., Menzies, K. J., & Auwerx, J. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.023 · Cited by 1,648
The 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
Self-citationPrice, N. L., Gomes, A. P., Ling, A. J. Y., Duarte, F. V., Martin-Montalvo, A., North, B. J., Agarwal, B., Ye, L., Ramadori, G., Teodoro, J. S., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.003 · Cited by 1,602
Self-citationGomes, A. P., Price, N. L., Ling, A. J. Y., Moslehi, J. J., Montgomery, M. K., Rajman, L., White, J. P., Teodoro, J. S., Wrann, C. D., Hubbard, B. P., et al. (2013) · Cell · doi:10.1016/j.cell.2013.11.037 · Cited by 1,482
Self-citationNAD+ 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
Sirt5 Is a NAD-Dependent Protein Lysine Demalonylase and Desuccinylase
Du, J., Zhou, Y., Su, X., Yu, J. J., Khan, S., Jiang, H., Kim, J., Woo, J., Kim, J. H., Choi, B. H., et al. (2011) · Science · doi:10.1126/science.1207861 · Cited by 1,429
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
Epigenetic protein families: a new frontier for drug discovery
Arrowsmith, C. H., Bountra, C., Fish, P. V., Lee, K., & Schapira, M. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3674 · Cited by 1,327
Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype
Wiley, C. D., Velarde, M. C., Lecot, P., Liu, S., Sarnoski, E. A., Freund, A., Shirakawa, K., Lim, H. W., Davis, S. S., Ramanathan, A., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.11.011 · Cited by 1,275
“, 2013a) that are linked to aging (Haigis and Sinclair, 2010; Merksamer et al., 2013)—for ability to regulate senescence, we identified the mitochondrial SIRTs SIRT3, and to a lesser extent SIRT5, as suppressors of senescence and modulators of the SASP.”
BackgroundMouchiroud, 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
Muscle wasting in disease: molecular mechanisms and promising therapies
Cohen, S., Nathan, J. A., & Goldberg, A. L. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4467 · Cited by 1,089
In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming.
Ocampo, A., Reddy, P., Martinez-Redondo, P., Platero-Luengo, A., Hatanaka, F., Hishida, T., Li, M., Lam, D., Kurita, M., Beyret, E., et al. (2016) · Cell · doi:10.1016/j.cell.2016.11.052 · Cited by 988
Influence of Metabolism on Epigenetics and Disease
Kaelin, W. G., & McKnight, S. L. (2013) · Cell · doi:10.1016/j.cell.2013.03.004 · Cited by 920
Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence
Rajman, L., Chwalek, K., & Sinclair, D. A. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.02.011 · Cited by 865
Self-citationPal, S., & Tyler, J. K. (2016) · Science Advances · doi:10.1126/sciadv.1600584 · Cited by 860
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
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
Self-citationThe Critical Role of Metabolic Pathways in Aging
Barzilai, N., Huffman, D. M., Muzumdar, R. H., & Bartke, A. (2012) · Diabetes · doi:10.2337/db11-1300 · Cited by 803
Molecular mechanisms of dietary restriction promoting health and longevity
Green, C. L., Lamming, D. W., & Fontana, L. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00411-4 · Cited by 714
Luen Tang, B. (2016) · Molecules and Cells · doi:10.14348/molcells.2016.2318 · Cited by 740
The acetylation of tau inhibits its function and promotes pathological tau aggregation
Cohen, T. J., Guo, J. L., Hurtado, D. E., Kwong, L. K., Mills, I. P., Trojanowski, J. Q., & Lee, V. M. Y. (2011) · Nature Communications · doi:10.1038/ncomms1255 · Cited by 724
PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes
Gupte, R., Liu, Z., & Kraus, W. L. (2017) · Genes & Development · doi:10.1101/gad.291518.116 · Cited by 681
“Like the PARP proteins, Sirt1 consumesNAD+ as a consequence of its catalytic activity, which promotes the deacetylation of lysine residues in proteins, generating O-acetyl-ADP-ribose (the acceptor of the acetyl group) and nicotinamide (Haigis and Sinclair 2010; Tong and Denu 2010).”
BackgroundTargeting inflammation in the treatment of type 2 diabetes: time to start
Donath, M. Y. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4275 · Cited by 690
Histone acetylation: molecular mnemonics on the chromatin
Gräff, J., & Tsai, L.-H. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3427 · Cited by 680
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
Self-citationNAD+ 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
Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining
Miller, K. M., Tjeertes, J. V., Coates, J., Legube, G., Polo, S. E., Britton, S., & Jackson, S. P. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1899 · Cited by 629
Absence 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
Quantitative Analysis of NAD Synthesis-Breakdown Fluxes
Liu, L., Su, X., Quinn, W. J., Hui, S., Krukenberg, K., Frederick, D. W., Redpath, P., Zhan, L., Chellappa, K., White, E., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.03.018 · Cited by 564
Chen, M., Zhu, X., Ran, L., Lang, H., Yi, L., & Mi, M. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.117.006347 · Cited by 600
The metabolic footprint of aging in mice
Houtkooper, R. H., Argmann, C., Houten, S. M., Cantó, C., Jeninga, E. H., Andreux, P. A., Thomas, C., Doenlen, R., Schoonjans, K., & Auwerx, J. (2011) · Scientific Reports · doi:10.1038/srep00134 · Cited by 528
A two-way street: reciprocal regulation of metabolism and signalling
Wellen, K. E., & Thompson, C. B. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3305 · Cited by 528
Impairment of an endothelial NAD(+)-H2S signaling network is a reversible cause of vascular aging
Das, A., Huang, G. X., Bonkowski, M. S., Longchamp, A., Li, C., Schultz, M. B., Kim, L.-J., Osborne, B., Joshi, S., Lu, Y., et al. (2018) · Cell · doi:10.1016/j.cell.2018.02.008 · Cited by 496
“SIRT1 is amember of the sirtuin family of NAD-dependent deacylases that mediate the health benefits of dietary restriction (DR) and can extend lifespan when overexpressed (Guarente, 2013; Haigis and Sinclair, 2010; Kanfi et al., 2012; Satoh et al., 2013).”
Self-citationGuarente, L. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1100831 · Cited by 510
AMPK at the Nexus of Energetics and Aging
Burkewitz, K., Zhang, Y., & Mair, W. B. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.03.002 · Cited by 483
The aging lung: Physiology, disease, and immunity
Schneider, J. L., Rowe, J. H., Garcia-de-Alba, C., Kim, C. F., Sharpe, A. H., & Haigis, M. C. (2021) · Cell · doi:10.1016/j.cell.2021.03.005 · Cited by 500
Self-citationCellular Metabolic Stress: Considering How Cells Respond to Nutrient Excess
Wellen, K. E., & Thompson, C. B. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.10.004 · Cited by 486
Sirtuin activators and inhibitors: Promises, achievements, and challenges
Dai, H., Sinclair, D. A., Ellis, J. L., & Steegborn, C. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.03.004 · Cited by 463
Self-citationFrom 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
NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells
Ratajczak, J., Joffraud, M., Trammell, S. A. J., Ras, R., Canela, N., Boutant, M., Kulkarni, S. S., Rodrigues, M., Redpath, P., Migaud, M. E., et al. (2016) · Nature Communications · doi:10.1038/ncomms13103 · Cited by 378
“Importantly, sirtuin activation has been associated with an improvement in metabolic efficiency and healthspan in mammals 4,5 .”
Sirt3 promotes the urea cycle and fatty acid oxidation during dietary restriction
Hallows, W. C., Yu, W., Smith, B. C., Devires, M. K., Ellinger, J. J., Someya, S., Shortreed, M. R., Prolla, T., Markley, J. L., Smith, L. M., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.01.002 · Cited by 389
The epigenetics of aging and neurodegeneration
Lardenoije, R., Iatrou, A., Kenis, G., Kompotis, K., Steinbusch, H. W. M., Mastroeni, D., Coleman, P., Lemere, C. A., Hof, P. R., van den Hove, D. L. A., et al. (2015) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.05.002 · Cited by 381
Li, X. (2013) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gms108 · Cited by 360
Mammalian Sirt1: insights on its biological functions
Rahman, S., & Islam, R. (2011) · Cell Communication and Signaling · doi:10.1186/1478-811x-9-11 · Cited by 362
Mitophagy in neurodegeneration and aging
Fivenson, E. M., Lautrup, S., Sun, N., Scheibye-Knudsen, M., Stevnsner, T., Nilsen, H., Bohr, V. A., & Fang, E. F. (2017) · Neurochemistry International · doi:10.1016/j.neuint.2017.02.007 · Cited by 364
Flavonoid Apigenin Is an Inhibitor of the NAD+ase CD38
Escande, C., Nin, V., Price, N. L., Capellini, V., Gomes, A. P., Barbosa, M. T., O’Neil, L., White, T. A., Sinclair, D. A., & Chini, E. N. (2013) · Diabetes · doi:10.2337/db12-1139 · Cited by 332
Self-citationLin, Z., Yang, H., Kong, Q., Li, J., Lee, S.-M., Gao, B., Dong, H., Wei, J., Song, J., Zhang, D. D., et al. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.03.024 · Cited by 315
SIRT3 regulation of mitochondrial oxidative stress
Bause, A. S., & Haigis, M. C. (2013) · Experimental Gerontology · doi:10.1016/j.exger.2012.08.007 · Cited by 311
Self-citationRestriction of Advanced Glycation End Products Improves Insulin Resistance in Human Type 2 Diabetes
Uribarri, J., Cai, W., Ramdas, M., Goodman, S., Pyzik, R., Chen, X., Zhu, L., Striker, G. E., & Vlassara, H. (2011) · Diabetes Care · doi:10.2337/dc11-0091 · Cited by 320
Epigenetic changes during aging and their reprogramming potential
Kane, A. E., & Sinclair, D. A. (2019) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2019.1570075 · Cited by 283
Self-citationEffects of aging on angiogenesis
Lähteenvuo, J., & Rosenzweig, A. (2012) · Circulation Research · doi:10.1161/circresaha.111.246116 · Cited by 292
Circadian Clocks and Metabolism
Marcheva, B., Ramsey, K. M., Peek, C. B., Affinati, A., Maury, E., & Bass, J. (2013) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-642-25950-0_6 · Cited by 282
Mitochondrial sirtuins: regulators of protein acylation and metabolism
He, W., Newman, J. C., Wang, M. Z., Ho, L., & Verdin, E. (2012) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2012.07.004 · Cited by 262
Chen, H.-Z., Wang, F., Gao, P., Pei, J.-F., Liu, Y., Xu, T.-T., Tang, X., Fu, W.-Y., Lu, J., Yan, Y.-F., et al. (2016) · Circulation Research · doi:10.1161/circresaha.116.308895 · Cited by 265
Regulation of metabolism: the circadian clock dictates the time
Sahar, S., & Sassone-Corsi, P. (2012) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2011.10.005 · Cited by 222
Impact of nutrients on circadian rhythmicity
Oosterman, J. E., Kalsbeek, A., la Fleur, S. E., & Belsham, D. D. (2015) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00322.2014 · Cited by 221
Lee, D., & Goldberg, A. L. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.489716 · Cited by 211
Joseph, A., Adhihetty, P. J., & Leeuwenburgh, C. (2016) · The Journal of Physiology · doi:10.1113/jp270659 · Cited by 186
The Role of Sirtuins in Cellular Homeostasis
Kupis, W., Pałyga, J., Tomal, E., & Niewiadomska, E. (2016) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-016-0492-6 · Cited by 200
Sirt1 enhances skeletal muscle insulin sensitivity in mice during caloric restriction
Schenk, S., McCurdy, C. E., Philp, A., Chen, M. Z., Holliday, M. J., Bandyopadhyay, G. K., Osborn, O., Baar, K., & Olefsky, J. M. (2011) · Journal of Clinical Investigation · doi:10.1172/jci58554 · Cited by 197
NAD + metabolism: A therapeutic target for age-related metabolic disease
Mouchiroud, L., Houtkooper, R. H., & Auwerx, J. (2013) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2013.789479 · Cited by 193
“Sirtuins are a class of metabolic regulators, of which seven orthologs exist in mammals (Blander & Guarente, 2004; Chalkiadaki & Guarente, 2012; Haigis & Sinclair, 2010; Houtkooper et al., 2012).”
BackgroundInfluentialGlycolysis: A multifaceted metabolic pathway and signaling hub
Kierans, S. J., & Taylor, C. T. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.107906 · Cited by 198
SIRT3 regulates mitochondrial protein acetylation and intermediary metabolism
Hirschey, M. D., Shimazu, T., Huang, J. Y., Schwer, B., & Verdin, E. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2011.76.010850 · Cited by 180
Efficient Demyristoylase Activity of SIRT2 Revealed by Kinetic and Structural Studies
Teng, Y.-B., Jing, H., Aramsangtienchai, P., He, B., Khan, S., Hu, J., Lin, H., & Hao, Q. (2015) · Scientific Reports · doi:10.1038/srep08529 · Cited by 184
NAD+ biosynthesis, aging, and disease
Johnson, S., & Imai, S. (2018) · F1000Research · doi:10.12688/f1000research.12120.1 · Cited by 178
Aging and reprogramming: a two-way street
Mahmoudi, S., & Brunet, A. (2012) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2012.10.004 · Cited by 171
Gomes, A. P., Duarte, F. V., Nunes, P., Hubbard, B. P., Teodoro, J. S., Varela, A. T., Jones, J. G., Sinclair, D. A., Palmeira, C. M., & Rolo, A. P. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.10.008 · Cited by 159
Self-citationRole of SIRT1 and FOXO factors in eNOS transcriptional activation by resveratrol
Xia, N., Strand, S., Schlufter, F., Siuda, D., Reifenberg, G., Kleinert, H., Förstermann, U., & Li, H. (2013) · Nitric Oxide · doi:10.1016/j.niox.2013.04.001 · Cited by 157
Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances
Jiang, Q., Liu, J., Huang, S., Wang, X.-Y., Chen, X., Liu, G.-H., Ye, K., Song, W., Masters, C. L., Wang, J., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02145-7 · Cited by 165
Histone deacetylases (HDACs) and brain function
Volmar, C.-H., & Wahlestedt, C. (2015) · Neuroepigenetics · doi:10.1016/j.nepig.2014.10.002 · Cited by 151
Calcium signaling alterations, oxidative stress, and autophagy in aging
Ureshino, R. P., Rocha, K. K., Lopes, G. S., Bincoletto, C., & Smaili, S. S. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5777 · Cited by 143
Nutrient-sensing pathways and metabolic regulation in stem cells
Ochocki, J. D., & Simon, M. C. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201303110 · Cited by 140
Haffner, C. D., Becherer, J. D., Boros, E. E., Cadilla, R., Carpenter, T., Cowan, D., Deaton, D. N., Guo, Y., Harrington, W., Henke, B. R., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/jm502009h · Cited by 137
Ralph, S. J., Moreno-Sánchez, R., Neuzil, J., & Rodríguez-Enríquez, S. (2011) · Pharmaceutical Research · doi:10.1007/s11095-011-0566-7 · Cited by 126
Shi, S., Lei, S., Tang, C., Wang, K., & Xia, Z. (2019) · Bioscience Reports · doi:10.1042/bsr20181614 · Cited by 135
Metformin Is a Direct SIRT1-Activating Compound: Computational Modeling and Experimental Validation
Cuyàs, E., Verdura, S., Llorach-Parés, L., Fernández-Arroyo, S., Joven, J., Martin-Castillo, B., Bosch-Barrera, J., Brunet, J., Nonell-Canals, A., Sanchez-Martinez, M., et al. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00657 · Cited by 122
Drosophila Sirt2/mammalian SIRT3 deacetylates ATP synthase β and regulates complex V activity
Rahman, M., Nirala, N. K., Singh, A., Zhu, L. J., Taguchi, K., Bamba, T., Fukusaki, E., Shaw, L. M., Lambright, D. G., Acharya, J. K., et al. (2014) · Journal of Cell Biology · doi:10.1083/jcb.201404118 · Cited by 116
Protective effects of sirtuin 3 in a murine model of sepsis-induced acute kidney injury
Zhao, W.-Y., Zhang, L., Sui, M.-X., Zhu, Y.-H., & Zeng, L. (2016) · Scientific Reports · doi:10.1038/srep33201 · Cited by 114
A nexus for cellular homeostasis: the interplay between metabolic and signal transduction pathways
Gomes, A. P., & Blenis, J. (2015) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2014.12.007 · Cited by 112
Biala, A., Tauriainen, E., Siltanen, A., Shi, J., Merasto, S., Louhelainen, M., Martonen, E., Finckenberg, P., Muller, D. N., & Mervaala, E. (2010) · Blood Pressure · doi:10.3109/08037051.2010.481808 · Cited by 97
Purushotham, A., Xu, Q., Lu, J., Foley, J. F., Yan, X., Kim, D.-H., Kemper, J. K., & Li, X. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.05988-11 · Cited by 87
Dollerup, O. L., Trammell, S. A. J., Hartmann, B., Holst, J. J., Christensen, B., Møller, N., Gillum, M. P., Treebak, J. T., & Jessen, N. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-01081 · Cited by 77
Generation, Release, and Uptake of the NAD Precursor Nicotinic Acid Riboside by Human Cells
Kulikova, V., Shabalin, K., Nerinovski, K., Dölle, C., Niere, M., Yakimov, A., Redpath, P., Khodorkovskiy, M., Migaud, M. E., Ziegler, M., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.664458 · Cited by 84
Aberrant protein acylation is a common observation in inborn errors of acyl-CoA metabolism
Pougovkina, O., te Brinke, H., Wanders, R. J. A., Houten, S. M., & de Boer, V. C. J. (2014) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-014-9684-9 · Cited by 80
Mitochondria and cellular senescence: Implications for musculoskeletal ageing
Habiballa, L., Salmonowicz, H., & Passos, J. F. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.10.417 · Cited by 82
Toward understanding genomic instability, mitochondrial dysfunction and aging
Fakouri, N. B., Hou, Y., Demarest, T. G., Christiansen, L. S., Okur, M. N., Mohanty, J. G., Croteau, D. L., & Bohr, V. A. (2019) · The FEBS Journal · doi:10.1111/febs.14663 · Cited by 77
Regulation of SIRT1 activity by genotoxic stress
Yuan, J., Luo, K., Liu, T., & Lou, Z. (2012) · Genes & Development · doi:10.1101/gad.188482.112 · Cited by 79
Dietary restriction: standing up for sirtuins
Baur, J. A., Chen, D., Chini, E. N., Chua, K., Cohen, H. Y., Cabo, R. D., Deng, C., Dimmeler, S., Gius, D., Guarente, L. P., et al. (2010) · Science · doi:10.1126/science.329.5995.1012 · Cited by 76
Self-citationDNA damage, chromatin, and transcription: the trinity of aging
Burgess, R. C., Misteli, T., & Oberdoerffer, P. (2012) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2012.07.005 · Cited by 72
Lugrin, J., Ciarlo, E., Santos, A., Grandmaison, G., Dos Santos, I., Le Roy, D., & Roger, T. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.03.004 · Cited by 67
Sirtuins at the Service of Healthy Longevity
Watroba, M., & Szukiewicz, D. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.724506 · Cited by 64
Decoding the Rosetta stone of mitonuclear communication
English, J., Son, J. M., Cardamone, M. D., Lee, C., & Perissi, V. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.105161 · Cited by 55
How does adipose tissue contribute to inflammageing?
Zamboni, M., Nori, N., Brunelli, A., & Zoico, E. (2021) · Experimental Gerontology · doi:10.1016/j.exger.2020.111162 · Cited by 55
A continuous, fluorogenic sirtuin 2 deacylase assay: substrate screening and inhibitor evaluation
Galleano, I., Schiedel, M., Jung, M., Madsen, A. S., & Olsen, C. A. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01532 · Cited by 53
Unraveling the Complexities of SIRT1-Mediated Mitochondrial Regulation in Skeletal Muscle
Philp, A., & Schenk, S. (2013) · Exercise and Sport Sciences Reviews · doi:10.1097/jes.0b013e3182956803 · Cited by 39
Why Is Longevity Still a Scientific Mystery? Sirtuins—Past, Present and Future
Ziętara, P., Dziewięcka, M., & Augustyniak, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010728 · Cited by 40
Metadata
- Authors
- Haigis, M. C., & Sinclair, D. A.
- Affiliations
- Harvard University (US)
- Venue
- Annual Review of Pathology: Mechanisms of Disease
- Publisher
- Annual Reviews
- Published
- 2010-01-01
- Volume
- 5
- Issue
- 1
- Pages
- 253-295
- ISSN
- 1553-4006 (ISSN-L)
- 1553-4014
- PMC
- PMC2866163
- OpenAlex
- W2118964113
- Cited by
- 2,085
- References
- 56
- Citations by year
- 2026: 78 · 2025: 118 · 2024: 80 · 2023: 113 · 2022: 123 · 2021: 152 · 2020: 143 · 2019: 124 · 2018: 148 · 2017: 115 · 2016: 142 · 2015: 117 · 2014: 154 · 2013: 145 · 2012: 149
- FWCI
- 13.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annual Review of Pathology Mechanisms of Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG032375, P01AG027916, R01AG028730, R01AG019719)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Keywords
- sirtuins, SIRT1, aging, healthspan, longevity, type 2 diabetes, neurodegenerative diseases, cancer, cardiovascular disease
- MeSH terms
- Aging, Animals, Cardiovascular Diseases, Humans, Longevity, Metabolic Diseases, Neoplasms, Neurodegenerative Diseases, Sirtuins
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
