Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila
Open accessAbstract
Overexpression of sirtuins (NAD(+)-dependent protein deacetylases) has been reported to increase lifespan in budding yeast (Saccharomyces cerevisiae), Caenorhabditis elegans and Drosophila melanogaster. Studies of the effects of genes on ageing are vulnerable to confounding effects of genetic background. Here we re-examined the reported effects of sirtuin overexpression on ageing and found that standardization of genetic background and the use of appropriate controls abolished the apparent effects in both C. elegans and Drosophila. In C. elegans, outcrossing of a line with high-level sir-2.1 overexpression abrogated the longevity increase, but did not abrogate sir-2.1 overexpression. Instead, longevity co-segregated with a second-site mutation affecting sensory neurons. Outcrossing of a line with low-copy-number sir-2.1 overexpression also abrogated longevity. A Drosophila strain with ubiquitous overexpression of dSir2 using the UAS-GAL4 system was long-lived relative to wild-type controls, as previously reported, but was not long-lived relative to the appropriate transgenic controls, and nor was a new line with stronger overexpression of dSir2. These findings underscore the importance of controlling for genetic background and for the mutagenic effects of transgene insertions in studies of genetic effects on lifespan. The life-extending effect of dietary restriction on ageing in Drosophila has also been reported to be dSir2 dependent. We found that dietary restriction increased fly lifespan independently of dSir2. Our findings do not rule out a role for sirtuins in determination of metazoan lifespan, but they do cast doubt on the robustness of the previously reported effects of sirtuins on lifespan in C. elegans and Drosophila.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Recent reports fail to show robust effects of SIRT on lifespan in C. elegans and Drosophila.
“recent reports fail to show robust effects of SIRT on lifespan in these same model systems (56).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [56]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
THE GENETICS OF CAENORHABDITIS ELEGANS
Brenner, S. (1974) · Genetics · doi:10.1093/genetics/77.1.71 · Cited by 14,984 · see citing works
Targeted gene expression as a means of altering cell fates and generating dominant phenotypes
Brand, A. H., & Perrimon, N. (1993) · Development · doi:10.1242/dev.118.2.401 · Cited by 9,510 · see citing works
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 · see citing works
Systematic functional analysis of the Caenorhabditis elegans genome using RNAi
Kamath, R. S., Fraser, A. G., Yan, D., Poulin, G. B., Durbin, R. M., Gotta, M., Kanapin, A. A., Bot, N. L., Moreno, S., Sohrmann, M., et al. (2003) · Nature · doi:10.1038/nature01278 · Cited by 3,542 · see citing works
The Nematode Caenorhabditis elegans
Wood, W. B. (1988) · Cold Spring Harbor Laboratory eBooks · Cited by 2,821 · see citing works
Kenyon, C. J. (2010) · Nature · doi:10.1038/nature08980 · Cited by 2,739 · see citing works
Kaeberlein, M., McVey, M., & Guarente, L. (1999) · Genes & Development · doi:10.1101/gad.13.19.2570 · Cited by 2,253 · see citing works
Self-citationMammalian Sirtuins: Biological Insights and Disease Relevance
Haigis, M. C., & Sinclair, D. A. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathol.4.110807.092250 · Cited by 2,085 · see citing works
Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans
Tissenbaum, H. A., & Guarente, L. (2001) · Nature · doi:10.1038/35065638 · Cited by 1,918 · see citing works
Sirtuin activators mimic caloric restriction and delay ageing in metazoans
Wood, J. G., Rogina, B., Lavu, S., Howitz, K., Helfand, S. L., Tatar, M., & Sinclair, D. (2004) · Nature · doi:10.1038/nature02789 · Cited by 1,868 · see citing works
Lin, S.-J., Defossez, P.-A., & Guarente, L. (2000) · Science · doi:10.1126/science.289.5487.2126 · Cited by 1,775 · see citing works
Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes
Milne, J. C., Lambert, P. D., Schenk, S., Carney, D. P., Smith, J. J., Gagne, D. J., Jin, L., Boss, O., Perni, R. B., Vu, C. B., et al. (2007) · Nature · doi:10.1038/nature06261 · Cited by 1,707 · see citing works
Sir2 mediates longevity in the fly through a pathway related to calorie restriction
Rogina, B., & Helfand, S. L. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404184101 · Cited by 1,361 · see citing works
Mechanism of Human SIRT1 Activation by Resveratrol
Borra, M. T., Smith, B. C., & Denu, J. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501250200 · Cited by 1,065 · see citing works
SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1
Pacholec, M., Bleasdale, J. E., Chrunyk, B., Cunningham, D., Flynn, D., Garofalo, R. S., Griffith, D., Griffor, M., Loulakis, P., Pabst, B., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.088682 · Cited by 915 · see citing works
Substrate-specific activation of sirtuins by resveratrol
Kaeberlein, M., McDonagh, T., Heltweg, B., Hixon, J., Westman, E. A., Caldwell, S. D., Napper, A., Curtis, R., DiStefano, P. S., Fields, S., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500655200 · Cited by 745 · see citing works
Self-citationGems, D., Sutton, A. J., Sundermeyer, M. L., Albert, P. S., King, K. V., Edgley, M. L., Larsen, P. L., & Riddle, D. L. (1998) · Genetics · doi:10.1093/genetics/150.1.129 · Cited by 718 · see citing works
Self-citationAging and Survival: The Genetics of Life Span Extension by Dietary Restriction
Mair, W. B., & Dillin, A. G. (2008) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.77.061206.171059 · Cited by 600 · see citing works
Regulation of lifespan by sensory perception in Caenorhabditis elegans
Apfeld, J., & Kenyon, C. (1999) · Nature · doi:10.1038/45544 · Cited by 573 · see citing works
Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons
Parker, J. A., Arango-Lievano, M., Abderrahmane, S., Lambert, E., Tourette, C., Catoire, H., & Néri, C. (2005) · Nature Genetics · doi:10.1038/ng1534 · Cited by 509 · see citing works
Hedgecock, E. M., Culotti, J. G., Thomson, J. N., & Perkins, L. A. (1985) · Developmental Biology · doi:10.1016/0012-1606(85)90443-9 · Cited by 435 · see citing works
Effects of resveratrol on lifespan in Drosophila melanogaster and Caenorhabditis elegans
Bass, T. M., Weinkove, D., Houthoofd, K., Gems, D., & Partridge, L. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2007.07.007 · Cited by 435 · see citing works
Self-citationResveratrol is not a direct activator of SIRT1 enzyme activity
Beher, D., Wu, J., Cumine, S., Kim, K. W., Lu, S., Atangan, L., & Wang, M. (2009) · Chemical Biology & Drug Design · doi:10.1111/j.1747-0285.2009.00901.x · Cited by 426 · see citing works
Lessons on longevity from budding yeast
Kaeberlein, M. R. (2010) · Nature · doi:10.1038/nature08981 · Cited by 420 · see citing works
Self-citationA Role for SIR-2.1 Regulation of ER Stress Response Genes in Determining C. elegans Life Span
Viswanathan, M., Kim, S. K., Berdichevsky, A., & Guarente, L. (2005) · Developmental Cell · doi:10.1016/j.devcel.2005.09.017 · Cited by 409 · see citing works
C. elegans SIR-2.1 Interacts with 14-3-3 Proteins to Activate DAF-16 and Extend Life Span
Berdichevsky, A., Viswanathan, M., Horvitz, H. R., & Guarente, L. (2006) · Cell · doi:10.1016/j.cell.2006.04.036 · Cited by 393 · see citing works
Sirtuins in Aging and DiseasePreprint
Guarente, L. (2007) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2007.72.024 · Cited by 371 · see citing works
Overlapping and distinct functions for a Caenorhabditis elegans SIR2 and DAF-16/FOXO
Wang, Y., & Tissenbaum, H. A. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2005.09.005 · Cited by 263 · see citing works
Partridge, L., & Gems, D. (2007) · Nature · doi:10.1038/450165a · Cited by 119 · see citing works
Self-citationGrandison, R. C., Wong, R., Bass, T. M., Partridge, L., & Piper, M. D. W. (2008) · PLoS ONE · doi:10.1371/journal.pone.0004067 · Cited by 104 · see citing works
Self-citationPatel, D. S., Garza-Garcı́a, A., Nanji, M. S., McElwee, J. J., Ackerman, D., Driscoll, P. C., & Gems, D. (2008) · Genetics · doi:10.1534/genetics.107.070813 · Cited by 96 · see citing works
Self-citationÅström, S. U., Cline, T. W., & Rine, J. (2003) · Genetics · doi:10.1093/genetics/163.3.931 · Cited by 83 · see citing works
Greiss, S., Hall, J., Ahmed, S., & Gartner, A. (2008) · Genes & Development · doi:10.1101/gad.482608 · Cited by 72 · see citing works
A Drosophila Homologue of Sir2 Modifies Position-Effect Variegation but Does Not Affect Life Span
Newman, B., Lundblad, J. R., Chen, Y., & Smolik, S. M. (2002) · Genetics · doi:10.1093/genetics/162.4.1675 · Cited by 66 · see citing works
Quantitative Assays for Characterization of the Sir2 Family of NAD+-Dependent Deacetylases
Borra, M. T., & Denu, J. M. (2003) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(03)76011-x · Cited by 42 · see citing works
A mid-life crisis for aging theory
Garber, K. (2008) · Nature Biotechnology · doi:10.1038/nbt0408-371 · Cited by 18 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982 · see citing works
Self-citationSirtuins as regulators of metabolism and healthspan
Houtkooper, R. H., Pirinen, E., & Auwerx, J. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3293 · Cited by 2,008 · see citing works
Cantó, C., Menzies, K. J., & Auwerx, J. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.023 · Cited by 1,648 · see citing works
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 · see citing works
Gomes, 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 · see citing works
NAD+ and sirtuins in aging and disease
Imai, S.-I., & Guarente, L. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.04.002 · Cited by 1,481 · see citing works
NAD <sup>+</sup> in aging, metabolism, and neurodegeneration
Verdin, E. (2015) · Science · doi:10.1126/science.aac4854 · Cited by 1,319 · see citing works
Timmers, S., Konings, E., Bilet, L., Houtkooper, R. H., van de Weijer, T., Goossens, G. H., Hoeks, J., van der Krieken, S., Ryu, D., Kersten, S., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.10.002 · Cited by 1,320 · see citing works
Ageing and the pathogenesis of osteoarthritis
Loeser, R. F., Collins, J. A., & Diekman, B. O. (2016) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2016.65 · Cited by 1,309 · see citing works
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 · see citing works
SIRT1 and other sirtuins in metabolism
Chang, H.-C., & Guarente, L. (2014) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2013.12.001 · Cited by 1,138 · see citing works
The sirtuin SIRT6 regulates lifespan in male mice
Kanfi, Y., Naiman, S., Amir, G., Peshti, V., Zinman, G., Nahum, L., Bar-Joseph, Z., & Cohen, H. Y. (2012) · Nature · doi:10.1038/nature10815 · Cited by 1,059 · see citing works
Solon-Biet, S. M., McMahon, A. C., Ballard, J. W. O., Ruohonen, K., Wu, L. E., Cogger, V. C., Warren, A., Huang, X., Pichaud, N., Melvin, R. G., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.02.009 · Cited by 904 · see citing works
AMP-Activated Protein Kinase (AMPK) Controls the Aging Process via an Integrated Signaling Network
Salminen, A., & Kaarniranta, K. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2011.12.005 · Cited by 860 · see citing works
Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds
Bonkowski, M. S., & Sinclair, D. A. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.93 · Cited by 834 · see citing works
The Role of Sirtuins in Antioxidant and Redox Signaling
Singh, C. K., Chhabra, G., Ndiaye, M. A., Garcia‐Peterson, L. M., Mack, N. J., & Ahmad, N. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7290 · Cited by 812 · see citing works
Senescence and aging: the critical roles of p53
Rufini, A., Tucci, P., Celardo, I., & Melino, G. (2013) · Oncogene · doi:10.1038/onc.2012.640 · Cited by 798 · see citing works
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 · see citing works
Gambini, J., Inglés, M., González, G. O., López-Grueso, R., Bonet-Costa, V., Gimeno-Mallench, L., Mas‐Bargues, C., Abdelaziz, K. M., Gómez‐Cabrera, M. C., Viña, J., et al. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/837042 · Cited by 752 · see citing works
Luen Tang, B. (2016) · Molecules and Cells · doi:10.14348/molcells.2016.2318 · Cited by 740 · see citing works
Satoh, A., Brace, C. S., Rensing, N., Cliften, P. F., Wozniak, D. F., Herzog, E. D., Yamada, K. A., & Imai, S. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.07.013 · Cited by 734 · see citing works
Madeo, F., Carmona-Gutierrez, D., Hofer, S. J., & Kroemer, G. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.01.018 · Cited by 630 · see citing works
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 · see citing works
Replicative and chronological aging in Saccharomyces cerevisiae
Longo, V. D., Shadel, G. S., Kaeberlein, M., & Kennedy, B. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.06.002 · Cited by 595 · see citing works
Self-citationRedox regulation of mitochondrial function
Handy, D. E., & Loscalzo, J. (2012) · Antioxidants & Redox Signaling · doi:10.1089/ars.2011.4123 · Cited by 588 · see citing works
Small molecule SIRT1 activators for the treatment of aging and age-related diseases
Hubbard, B. P., & Sinclair, D. A. (2014) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.12.004 · Cited by 572 · see citing works
Genetics of Longevity in Model Organisms: Debates and Paradigm Shifts
Gems, D., & Partridge, L. (2012) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183712 · Cited by 545 · see citing works
Self-citationInsulin/insulin-like growth factor signaling in C. elegans
Murphy, C. T. (2013) · WormBook · doi:10.1895/wormbook.1.164.1 · Cited by 527 · see citing works
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 · see citing works
Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS)
Ristow, M., & Schmeisser, K. (2014) · Dose-Response · doi:10.2203/dose-response.13-035.ristow · Cited by 534 · see citing works
Metabolism and the Circadian Clock Converge
Eckel‐Mahan, K. L., & Sassone‐Corsi, P. (2013) · Physiological Reviews · doi:10.1152/physrev.00016.2012 · Cited by 530 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Calorie restriction and sirtuins revisited
Guarente, L. (2013) · Genes & Development · doi:10.1101/gad.227439.113 · Cited by 464 · see citing works
Crosstalk between Oxidative Stress and SIRT1: Impact on the Aging Process
Salminen, A., Kaarniranta, K., & Kauppinen, A. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms14023834 · Cited by 457 · see citing works
Resveratrol and Clinical Trials: The Crossroad from In Vitro Studies to Human Evidence
Tomé‐Carneiro, J., Larrosa, M., González‐Sarrías, A., Tomás-Barberán, F. A., García‐Conesa, M., & Espı́n, J. C. (2013) · Current Pharmaceutical Design · doi:10.2174/13816128113199990407 · Cited by 451 · see citing works
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 438 · see citing works
SIRT3 Reverses Aging-Associated Degeneration
Brown, K., Xie, S., Qiu, X., Mohrin, M., Shin, J., Liu, Y., Zhang, D., Scadden, D. T., & Chen, D. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.01.005 · Cited by 436 · see citing works
De novo NAD+ synthesis enhances mitochondrial function and improves health
Katsyuba, E., Mottis, A., Ziętak, M., Franco, F., van der Velpen, V., Gariani, K., Ryu, D., Cialabrini, L., Matilainen, O., Liscio, P., et al. (2018) · Nature · doi:10.1038/s41586-018-0645-6 · Cited by 436 · see citing works
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 · see citing works
Mechanisms Regulating Neuromuscular Junction Development and Function and Causes of Muscle Wasting
Tintignac, L. A. J., Brenner, H.-R., & Rüegg, M. A. (2015) · Physiological Reviews · doi:10.1152/physrev.00033.2014 · Cited by 422 · see citing works
Cellular stress responses, hormetic phytochemicals and vitagenes in aging and longevity
Calabrese, V., Cornelius, C., Dinkova‐Kostova, A. T., Iavicoli, I., Paola, R. D., Koverech, A., Cuzzocrea, S., Rizzarelli, E., & Calabrese, E. J. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.11.002 · Cited by 420 · see citing works
SIRT1 and SIRT2: emerging targets in neurodegeneration
Dönmez, G., & Outeiro, T. F. (2013) · EMBO Molecular Medicine · doi:10.1002/emmm.201302451 · Cited by 414 · see citing works
It takes two to tango: NAD(+) and sirtuins in aging/longevity control
Imai, S.-I., & Guarente, L. (2016) · npj Aging and Mechanisms of Disease · doi:10.1038/npjamd.2016.17 · Cited by 394 · see citing works
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 · see citing works
Axis of ageing: telomeres, p53 and mitochondria
Sahin, E., & DePinho, R. A. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3352 · Cited by 380 · see citing works
Are 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 389 · see citing works
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 380 · see citing works
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 367 · see citing works
<b><i>FOXO3:</i></b> A Major Gene for Human Longevity - A Mini-Review
Morris, B. J., Willcox, D. C., Donlon, T. A., & Willcox, B. J. (2015) · Gerontology · doi:10.1159/000375235 · Cited by 353 · see citing works
Sirtuin activators and inhibitors
Villalba, J. M., & Alcain, F. J. (2012) · BioFactors · doi:10.1002/biof.1032 · Cited by 353 · see citing works
Sirtuins in Renal Health and Disease
Morigi, M., Perico, L., & Benigni, A. (2018) · Journal of the American Society of Nephrology · doi:10.1681/asn.2017111218 · Cited by 359 · see citing works
The Search for Antiaging Interventions: From Elixirs to Fasting Regimens
de Cabo, R., Carmona-Gutierrez, D., Bernier, M., Hall, M. N., & Madeo, F. (2014) · Cell · doi:10.1016/j.cell.2014.05.031 · Cited by 345 · see citing works
Dietary restriction and lifespan: lessons from invertebrate models
Kapahi, P., Kaeberlein, M., & Hansen, M. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.12.005 · Cited by 340 · see citing works
Self-citationOrozco, H., Matallana, E., & Aranda, A. (2013) · Microbial Cell Factories · doi:10.1186/1475-2859-12-1 · Cited by 300 · see citing works
Effects of aging on angiogenesis
Lähteenvuo, J., & Rosenzweig, A. (2012) · Circulation Research · doi:10.1161/circresaha.111.246116 · Cited by 292 · see citing works
Donohoe, D. R., & Bultman, S. J. (2012) · Journal of Cellular Physiology · doi:10.1002/jcp.24054 · Cited by 296 · see citing works
Effect of Antioxidants Supplementation on Aging and Longevity
Sadowska‐Bartosz, I., & Bartosz, G. (2014) · BioMed Research International · doi:10.1155/2014/404680 · Cited by 298 · see citing works
Strategies for Reducing or Preventing the Generation of Oxidative Stress
Poljšak, B. (2011) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2011/194586 · Cited by 287 · see citing works
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 280 · see citing works
The sirtuins, oxidative stress and aging: an emerging link
Merksamer, P. I., Liu, Y., He, W., Hirschey, M. D., Chen, D., & Verdin, E. (2013) · Aging · doi:10.18632/aging.100544 · Cited by 275 · see citing works
Menssen, A., Hydbring, P., Kapelle, K., Vervoorts, J., Diebold, J., Lüscher, B., Larsson, L., & Hermeking, H. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1105304109 · Cited by 275 · see citing works
Lifespan and healthspan extension by resveratrol
Bhullar, K. S., & Hubbard, B. P. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.01.012 · Cited by 273 · see citing works
Sirtuins in Epigenetic Regulation
Jing, H., & Lin, H. (2015) · Chemical Reviews · doi:10.1021/cr500457h · Cited by 271 · see citing works
NAD metabolism: Implications in aging and longevity
Yaku, K., Okabe, K., & Nakagawa, T. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.05.006 · Cited by 269 · see citing works
The role of mitochondrial DNA mutations and free radicals in disease and ageing
Lagouge, M., & Larsson, N. (2013) · Journal of Internal Medicine · doi:10.1111/joim.12055 · Cited by 270 · see citing works
Nicotinamide-induced Mitophagy
Jang, S., Kang, H. T., & Hwang, E. S. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.363747 · Cited by 259 · see citing works
Emerging Role of Sirtuin 2 in the Regulation of Mammalian Metabolism
Gomes, P., Outeiro, T. F., & Cavadas, C. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.08.001 · Cited by 253 · see citing works
SIRT3, a pivotal actor in mitochondrial functions: metabolism, cell death and aging
Giralt, A., & Villarroya, F. (2012) · Biochemical Journal · doi:10.1042/bj20120030 · Cited by 253 · see citing works
Crosstalk between poly(ADP-ribose) polymerase and sirtuin enzymes
Cantó, C., Sauve, A. A., & Bai, P. (2013) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2013.01.004 · Cited by 246 · see citing works
Tsurumi, A., & Li, W. X. (2012) · Epigenetics · doi:10.4161/epi.20540 · Cited by 248 · see citing works
Sorting out functions of sirtuins in cancer
Roth, M., & Chen, W. (2013) · Oncogene · doi:10.1038/onc.2013.120 · Cited by 239 · see citing works
Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide
Schmeisser, K., Mansfeld, J., Kuhlow, D., Weimer, S., Priebe, S., Heiland, I., Birringer, M., Groth, M., Segref, A., Kanfi, Y., et al. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1352 · Cited by 236 · see citing works
Mitochondrial Metabolism, Sirtuins, and AgingPreprint
Sack, M. N., & Finkel, T. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a013102 · Cited by 237 · see citing works
The sirtuin family’s role in aging and age-associated pathologies
Hall, J. A., Dominy, J. E., Lee, Y., & Puigserver, P. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64094 · Cited by 235 · see citing works
The importance of NAMPT / NAD / SIRT1 in the systemic regulation of metabolism and ageing
Imai, S., & Yoshino, J. (2013) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12171 · Cited by 232 · see citing works
From Sirtuin Biology to Human Diseases: An Update
Sebastián, C., Satterstrom, F. K., Haigis, M. C., & Mostoslavsky, R. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r112.402768 · Cited by 228 · see citing works
Sirtuins, epigenetics and longevity
Wątroba, M., Dudek, I., Skoda, M., Stangret, A., Rzodkiewicz, P., & Szukiewicz, D. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.08.001 · Cited by 222 · see citing works
Measurement of Lifespan in Drosophila melanogaster
Linford, N. J., Bilgir, C., Ro, J., & Pletcher, S. D. (2013) · Journal of Visualized Experiments · doi:10.3791/50068 · Cited by 221 · see citing works
The endothelium: influencing vascular smooth muscle in many ways
Triggle, C. R., Samuel, S. M., Ravishankar, S., Marei, I., Arunachalam, G., & Ding, H. (2012) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y2012-073 · Cited by 218 · see citing works
Changes in Regenerative Capacity through Lifespan
Yun, M. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms161025392 · Cited by 216 · see citing works
Wood, J. G., Jones, B. C., Jiang, N., Chang, C., Hosier, S., Wickremesinghe, P., Garcia, M., Hartnett, D. A., Burhenn, L., Neretti, N., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1604621113 · Cited by 214 · see citing works
Liu, B., Ghosh, S., Yang, X., Zheng, H., Liu, X., Wang, Z., Jin, G., Zheng, B., Kennedy, B. K., Suh, Y., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.11.007 · Cited by 211 · see citing works
Self-citationNovel insights into ChREBP regulation and function
Filhoulaud, G., Guilmeau, S., Dentin, R., Girard, J. R., & Postic, C. (2013) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2013.01.003 · Cited by 211 · see citing works
Bana, B., & Cabreiro, F. (2019) · Annual Review of Genetics · doi:10.1146/annurev-genet-112618-043650 · Cited by 207 · see citing works
Self-citationSharples, A. P., Hughes, D. C., Deane, C. S., Saini, A. S., Selman, C., & Stewart, C. E. (2015) · Aging Cell · doi:10.1111/acel.12342 · Cited by 200 · see citing works
The neurobiology of sirtuins and their role in neurodegeneration
Dönmez, G. (2012) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2012.05.007 · Cited by 195 · see citing works
Lifespan-regulating genes in C. elegans
Uno, M., & Nishida, E. (2016) · npj Aging and Mechanisms of Disease · doi:10.1038/npjamd.2016.10 · Cited by 192 · see citing works
Sirtuins' modulation of autophagy
Ng, F., & Tang, B. L. (2013) · Journal of Cellular Physiology · doi:10.1002/jcp.24399 · Cited by 194 · see citing works
Resveratrol as a calorie restriction mimetic: therapeutic implications
Chung, J. H., Manganiello, V., & Dyck, J. R. B. (2012) · Trends in Cell Biology · doi:10.1016/j.tcb.2012.07.004 · Cited by 192 · see citing works
NAD <sup>+</sup> 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 · see citing works
“1 and fly SIR2 on lifespan is, at best, limited or even absent (Burnett et al., 2011; Viswanathan & Guarente, 2011).”
BackgroundSirtuins at the crossroads of stemness, aging, and cancer
O'Callaghan, C., & Vassilopoulos, A. (2017) · Aging Cell · doi:10.1111/acel.12685 · Cited by 187 · see citing works
Coming of age: molecular drivers of aging and therapeutic opportunities
Newgard, C. B., & Sharpless, N. E. (2013) · Journal of Clinical Investigation · doi:10.1172/jci68833 · Cited by 186 · see citing works
SIRT1 in the brain—connections with aging-associated disorders and lifespan
Ng, F. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00064 · Cited by 185 · see citing works
Circulatory miR-34a as an RNA-based, noninvasive biomarker for brain aging
Li, X., Khanna, A., Li, N., & Wang, E. (2011) · Aging · doi:10.18632/aging.100371 · Cited by 183 · see citing works
Axonal Degeneration during Aging and Its Functional Role in Neurodegenerative Disorders
Salvadores, N., Sanhueza, M., Manque, P., & Court, F. A. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00451 · Cited by 182 · see citing works
Angulo, J., Assar, M. E., & Rodríguez‐Mañas, L. (2016) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2016.06.001 · Cited by 185 · see citing works
The Metabolic Impact on Histone Acetylation and Transcription in Ageing
Peleg, S., Feller, C., Ladurner, A. G., & Imhof, A. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2016.05.008 · Cited by 178 · see citing works
Imiquimod has strain-dependent effects in mice and does not uniquely model human psoriasis
Swindell, W. R., Michaels, K. A., Sutter, A. J., Diaconu, D., Fritz, Y., Xing, X., Sarkar, M. K., Liang, Y., Tsoi, L. C., Gudjonsson, J. E., et al. (2017) · Genome Medicine · doi:10.1186/s13073-017-0415-3 · Cited by 177 · see citing works
- Authors
- Burnett, C., Valentini, S., Cabreiro, F., Goss, M., Somogyvári, M., Piper, M. D., Hoddinott, M., Sutphin, G. L., Leko, V., McElwee, J. J., Vazquez-Manrique, R. P., Orfila, A.-M., Ackerman, D., Au, C., Vinti, G., Riesen, M., Howard, K., Neri, C., Bedalov, A., Kaeberlein, M., Sőti, C., Partridge, L., & Gems, D.
- Affiliations
- University College London (GB)
- Semmelweis University (HU)
- University of Washington (US)
- Fred Hutch Cancer Center (US)
- Inserm (FR)
- MRC Laboratory for Molecular Cell Biology (GB)
- Max Planck Institute for Biology of Ageing (DE)
- Corresponding author
- Gems, David
- ORCID
- Venue
- Nature
- Published
- 2011-09
- Volume
- 477
- Issue
- 7365
- Pages
- 482-485
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3188402
- OpenAlex
- W2074974899
- Cited by
- 624
- References
- 36
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 16 · 2023: 15 · 2022: 19 · 2021: 23 · 2020: 18 · 2019: 33 · 2018: 26 · 2017: 43 · 2016: 54 · 2015: 71 · 2014: 60 · 2013: 98 · 2012: 100
- FWCI
- 32.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Funders
- Wellcome Trust (081394)
- European Commission
- National Institutes of Health
- National Institute on Aging (R01AG031108, T32AG000057)
- National Cancer Institute (CA129132, R01CA129132)
- National Center for Research Resources
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- Sir2, sirtuins, lifespan extension, aging, dietary restriction, Caenorhabditis elegans, Drosophila melanogaster, outcrossing, sensory neurons, NAD+-dependent deacetylase
- MeSH terms
- Aging, Animals, Crosses, Genetic, Drosophila melanogaster, Female, Histone Deacetylases, Longevity, Male, RNA, Messenger, Gene Expression, Caenorhabditis elegans, Drosophila Proteins, Caenorhabditis elegans Proteins, Animals, Genetically Modified, Caloric Restriction, 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
