Cited by 238Genetics, Aging, and Longevity in Model OrganismsSirtuins and Resveratrol in MedicineAutophagy in Disease and Therapy

The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.

Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide

Open access

Schmeisser, Kathrin, Mansfeld, Johannes, Kuhlow, Doreen, Weimer, Sandra, Priebe, Steffen, Heiland, Ines, Birringer, Marc, Groth, Marco, Segref, Alexandra, Kanfi, Yariv, Price, Nathan L, Schmeisser, Sebastian, Schuster, Stefan, Pfeiffer, Andreas F H, Guthke, Reinhard, Platzer, Matthias, Hoppe, Thorsten, Cohen, Haim Y, Zarse, Kim, Sinclair, David A, Ristow, Michael·2013·Nature Chemical Biology

DOI 10.1038/nchembio.1352PMC PMC4076143

Open this paper in CoChat — free account

Abstract

Sirtuins, a family of histone deacetylases, have a fiercely debated role in regulating lifespan. In contrast with recent observations, here we find that overexpression of sir-2.1, the ortholog of mammalian SirT1, does extend Caenorhabditis elegans lifespan. Sirtuins mandatorily convert NAD(+) into nicotinamide (NAM). We here find that NAM and its metabolite, 1-methylnicotinamide (MNA), extend C. elegans lifespan, even in the absence of sir-2.1. We identify a previously unknown C. elegans nicotinamide-N-methyltransferase, encoded by a gene now named anmt-1, to generate MNA from NAM. Disruption and overexpression of anmt-1 have opposing effects on lifespan independent of sirtuins, with loss of anmt-1 fully inhibiting sir-2.1-mediated lifespan extension. MNA serves as a substrate for a newly identified aldehyde oxidase, GAD-3, to generate hydrogen peroxide, which acts as a mitohormetic reactive oxygen species signal to promote C. elegans longevity. Taken together, sirtuin-mediated lifespan extension depends on methylation of NAM, providing an unexpected mechanistic role for sirtuins beyond histone deacetylation.

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

Crossref · 10.1038/nchembio.1352

Cites

56 of 56 references verified0 citation errors · 0 not checkable

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

<tt>edgeR</tt> : a Bioconductor package for differential expression analysis of digital gene expression data
Robinson, M. D., McCarthy, D. J., & Smyth, G. K. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btp616 · Cited by 41,364
Differential expression analysis for sequence count data
Anders, S., & Huber, W. (2010) · Genome Biology · doi:10.1186/gb-2010-11-10-r106 · Cited by 15,581
TopHat: discovering splice junctions with RNA-Seq
Trapnell, C., Pachter, L. S., & Salzberg, S. L. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp120 · Cited by 11,682
Health benefits of physical activity: the evidence
Warburton, D. E. R. (2006) · Canadian Medical Association Journal · doi:10.1503/cmaj.051351 · Cited by 8,007
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
The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms
Kaeberlein, M., McVey, M., & Guarente, L. (1999) · Genes & Development · doi:10.1101/gad.13.19.2570 · Cited by 2,253
Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women
Nordestgaard, B. G., Benn, M., Schnohr, P., & Tybjærg-Hansen, A. (2007) · JAMA · doi:10.1001/jama.298.3.299 · Cited by 2,058
Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease
Brown, B. G., Zhao, X.-Q., Chait, A., Fisher, L. D., Cheung, M. C., Morse, J. S., Dowdy, A. A., Marino, E. K., Bolson, E. L., Alaupovic, P., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa011090 · Cited by 1,979
Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin
Canner, P. L., Berge, K. G., Wenger, N. K., Stamler, J., Friedman, L., Prineas, R. J., & Friedewald, W. (1986) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(86)80293-5 · Cited by 1,824
Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans
Tissenbaum, H. A., & Guarente, L. (2001) · Nature · doi:10.1038/35065638 · Cited by 1,603

Flagged first, then by citations

Show all 56 references

Sorted by citations

Items 201–238 of 238

Potential mechanisms of exercise in maintaining skin homeostasis disrupted by protein deficiency (Review)
Kastella, F., Tarawan, V. M., Setiawan, I., Gunawan, D., Jasaputra, D. K., Goenawan, H., Gunadi, J. W., & Lesmana, R. (2024) · World Academy of Sciences Journal · doi:10.3892/wasj.2024.235 · Cited by 2
Novel NAD+ metabolomic technologies and their applications to Nicotinamide Riboside interventions
Trammell, S. A. J., Wright, M. E., Piper, R. C., Brenner, C., Slusarski, D. C., & Wilson, M. E. (2016) · doi:10.17077/etd.mk206led · Cited by 1
Genetic and functional diversification of chemosensory pathway receptors in mosquito-borne filarial nematodesPreprint
Wheeler, N. J., Heimark, Z. W., Airs, P. M., Mann, A., Bartholomay, L. C., & Zamanian, M. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/683060 · Cited by 1
Lactate promotes longevity through redox-driven lipid remodeling in Caenorhabditis elegansPreprint
Tauffenberger, A., Netherland, P. J., Fiumelli, H., Meisel, J. D., Schroeder, F. C., & Magistretti, P. J. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.25.678523 · Cited by 1
Ageing in the mammalian brain
Khojah, S. M. (2015) · Enlighten: Theses (The University of Glasgow)
Cellular Longevity of Budding Yeast During Replicative and Chronological Aging
Choi, K.-M., & Lee, C. (2015) · Springer eBooks · doi:10.1007/978-4-431-55763-0_6
Untersuchungen zur Rolle des Silent information regulator 2 (Sirt2) im experimentellen Schlaganfall in Mäusen
Krey, L. (2019) · doi:10.53846/goediss-7569
PARTIAL INHIBITION OF MITOCHONDRIAL COMPLEX I ACTIVATES STRESS RESPONSE PATHWAYS INDUCING A PROTECTION AGAINST OXIDATIVE STRESS
Tripathi, U. (2017) · OakTrust (Texas A&M University Libraries)
Sirtuins and life span extension
Lee, S., & Min, K. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-814118-2.00006-9
Quantum Computational, Spectroscopic, NHO and Molecular Docking Studies on 1-Methyl-nicotinamide (MNA): An Antithrombotic, Anti-inflammatory, Gastroprotective and Vasoprotective Compound
Kumar, M., Singh, S., Siddiqui, N., & Javed, S. (2021) · Asian Journal of Organic & Medicinal Chemistry · doi:10.14233/ajomc.2021.ajomc-p326
Control of Mitochondrial Homeostasis In Disused and Aging Skeletal Muscle: Role of Pgc-1Alpha and Sirtuins
Yeo, D. (2020) · University of Minnesota Digital Conservancy (University of Minnesota)
NNMT Promotes Aerobic Glycolysis and Tumorigenesis by Upregulating EGFR Expression in CholangiocarcinomaPreprint
Lu, S., Ke, S., Wang, C., Xu, Y., Li, Z., Song, K., Bai, M., Zhou, M., Yu, H., Yin, B., et al. (2021) · SSRN Electronic Journal · doi:10.2139/ssrn.3981540
Introduction
Ghosh, S. (2019) · Springer theses · doi:10.1007/978-981-32-9267-3_1
Toxicological assessment of silica particles functionalised with essential oil components and their constituents
López, C. F. (2022) · doi:10.4995/thesis/10251/181634
Faculty Opinions recommendation of D-Glucosamine supplementation extends life span of nematodes and of ageing mice.
Mobasheri, A., & Mendes, A. F. (2014) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.718342636.793498083
Ribosídeo de nicotinamida (NR), uma molécula doadora de NAD+, falha em ativar o metabolismo e retardar o envelhecimento em "Caenorhabditis elegans"
da Silva, G. T. (2020) · doi:10.47749/t/unicamp.2020.1128746
Nicotinamide- N -methyltransferase is essential for SAM and 1-methylnicotinamide homeostasis in the AML12 hepatocyte cell linePreprint
Yoda, M., Mizuno, R., Izumi, Y., Takahashi, M., Bamba, T., & Kawaoka, S. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.09.25.509348
Nutraceuticals for targeting NAD+ to restore mitochondrial function
Garten, A., & Lavery, G. G. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-90256-4.00019-9
Resolving Geroplasticity to the Balance of Rejuvenins and Geriatrins
TABIBZADEH, S. S. (2022) · Aging and Disease · doi:10.14336/ad.2022.0414
Molecular Mechanisms of Cancer Metabolism and Their Cellular Cycles
Ganga, H., & Appavu, R. (2022) · Journal of Student Research · doi:10.47611/jsrhs.v11i3.3418
Atherosclerosis as Age-Related Disease: The Potential of Sirtuins Treatment
Poznyak, A. V., Glanz, V. Y., Sukhorukov, V. N., Melnichenko, A. A., Pleshko, E. M., Golovyuk, A. L., & Orekhov, A. N. (2024) · OnLine Journal of Biological Sciences · doi:10.3844/ojbsci.2024.503.514
A Novel Fasting Mimetic (Mimio™) Improves Hunger, Digestion, Oxidative Stress, and Cardiometabolic Markers in Overweight Adults with Elevated HbA1c: a Double-Blind, Randomized, Placebo-Controlled TrialPreprint
Grant, A. D., Erfe, M. C. B., Kazaryan, A., Oliver, P. L., Moos, J., Luna, V., Craft, N., & Rhodes, C. H. (2025) · medRxiv · doi:10.1101/2025.04.30.25326755
An Obscure Natural NAD + -Boosting Sirtuin Activator: N 1 -Methylnicotinamide (1-MNA)Preprint
Alpay, F. (2025) · doi:10.22541/au.175312720.01281720/v1
Sirtuin downregulation mediates mitochondrial impairment causing cognitive decline in hepatic encephalopathy
Gupta, S., Rishi, V., & Aggarwal, A. (2025) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2025.11.049
Additional file 3 of PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease
Thejer, B. M., Adhikary, P. P., Teakel, S. L., Fang, J., Weston, P. A., Gurusinghe, S., Anwer, A. G., Gosnell, M. E., Jazayeri, J. A., Ludescher, M., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12134406
Additional file 5 of PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease
Thejer, B. M., Adhikary, P. P., Teakel, S. L., Fang, J., Weston, P. A., Gurusinghe, S., Anwer, A. G., Gosnell, M. E., Jazayeri, J. A., Ludescher, M., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12134418
Additional file 9 of PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease
Thejer, B. M., Adhikary, P. P., Teakel, S. L., Fang, J., Weston, P. A., Gurusinghe, S., Anwer, A. G., Gosnell, M. E., Jazayeri, J. A., Ludescher, M., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12134451
Additional file 7 of PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease
Thejer, B. M., Adhikary, P. P., Teakel, S. L., Fang, J., Weston, P. A., Gurusinghe, S., Anwer, A. G., Gosnell, M. E., Jazayeri, J. A., Ludescher, M., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12134430
Additional file 4 of PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease
Thejer, B. M., Adhikary, P. P., Teakel, S. L., Fang, J., Weston, P. A., Gurusinghe, S., Anwer, A. G., Gosnell, M. E., Jazayeri, J. A., Ludescher, M., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12134412
Additional file 1 of PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease
Thejer, B. M., Adhikary, P. P., Teakel, S. L., Fang, J., Weston, P. A., Gurusinghe, S., Anwer, A. G., Gosnell, M. E., Jazayeri, J. A., Ludescher, M., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12134391
Additional file 6 of PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease
Thejer, B. M., Adhikary, P. P., Teakel, S. L., Fang, J., Weston, P. A., Gurusinghe, S., Anwer, A. G., Gosnell, M. E., Jazayeri, J. A., Ludescher, M., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12134421
Additional file 10 of PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease
Thejer, B. M., Adhikary, P. P., Teakel, S. L., Fang, J., Weston, P. A., Gurusinghe, S., Anwer, A. G., Gosnell, M. E., Jazayeri, J. A., Ludescher, M., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12134373
Additional file 8 of PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease
Thejer, B. M., Adhikary, P. P., Teakel, S. L., Fang, J., Weston, P. A., Gurusinghe, S., Anwer, A. G., Gosnell, M. E., Jazayeri, J. A., Ludescher, M., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12134442
Additional file 2 of PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease
Thejer, B. M., Adhikary, P. P., Teakel, S. L., Fang, J., Weston, P. A., Gurusinghe, S., Anwer, A. G., Gosnell, M. E., Jazayeri, J. A., Ludescher, M., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12134400
Développement d'outils pour l'étude de méthyltransférases d'ARN : synthèse de 1,2,3-triazoles pour accéder à des conjugués SAM-ARN
Coelho, D. (2023) · doi:10.70675/d2cc8a8ez6858z4e88z8dd3za1a49f0bc4b0
BindingDB Entry 7479: A Rapid and Efficient Assay for the Characterization of Substrates and Inhibitors of Nicotinamide N-Methyltransferase.
BindingDB (2016) · UC San Diego · doi:10.7270/q2h130th
BindingDB Entry 50000365: Discovery of Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT).
BindingDB (2019) · UC San Diego · doi:10.7270/q2ft8pf2
Management of nicotinamide N-methyltransferase overexpression: inhibit the enzyme or reduce nicotinamide intake? Reply to Zhou S, Li D, Zhou Y [letter]
Kannt, A., Pfenninger, A., Tönjes, A., & Blüher, M. (2015) · Diabetologia · doi:10.1007/s00125-015-3678-5

Authors: Schmeisser, K., Mansfeld, J., Kuhlow, D., Weimer, S., Priebe, S., Heiland, I., Birringer, M., Groth, M., Segref, A., Kanfi, Y., Price, N. L., Schmeisser, S., Schuster, S., Pfeiffer, A. F. H., Guthke, R., Platzer, M., Hoppe, T., Cohen, H. Y., Zarse, K., Sinclair, D. A., & Ristow, M.
Affiliations: Friedrich Schiller University Jena (DE)
ETH Zurich (CH)
German Institute of Human Nutrition (DE)
Fulda University of Applied Sciences (DE)
Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
University of Cologne (DE)
Bar-Ilan University (IL)
Harvard University (US)
Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
Corresponding author: Ristow, Michael
ORCID: Schmeisser, Kathrin
Heiland, Ines
Birringer, Marc
Groth, Marco
Segref, Alexandra
Price, Nathan L
Schmeisser, Sebastian
Schuster, Stefan
Pfeiffer, Andreas F H
Platzer, Matthias
Hoppe, Thorsten
Cohen, Haim Y
Zarse, Kim
Sinclair, David A
Ristow, Michael
Venue: Nature Chemical Biology
Publisher: Springer Science and Business Media LLC
Published: 2013-09-29
Volume: 9
Issue: 11
Pages: 693-700
ISSN: 1552-4450 (ISSN-L)
1552-4469
DOI: 10.1038/nchembio.1352
PMC: PMC4076143
OpenAlex: W1974979950
Cited by: 236
References: 56
Citations by year: 2026: 2 · 2025: 12 · 2024: 14 · 2023: 14 · 2022: 25 · 2021: 20 · 2020: 27 · 2019: 18 · 2018: 17 · 2017: 15 · 2016: 20 · 2015: 27 · 2014: 22 · 2013: 3
FWCI: 8.63
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature Chemical Biology (publishedVersion)
PubMed (publishedVersion)
Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (P40OD010440)
National Institute on Aging (R37AG028730)
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 › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Keywords: sirtuins, SIRT1, sir-2.1, lifespan extension, Caenorhabditis elegans, nicotinamide, N1-methylnicotinamide, nicotinamide N-methyltransferase, aldehyde oxidase, hydrogen peroxide, mitohormesis, reactive oxygen species signaling, NAD+ metabolism, longevity
MeSH terms: Animals, Longevity, Methylation, Niacinamide, Caenorhabditis elegans, Caenorhabditis elegans Proteins, 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

Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks