ArticleNature chemical biology2013
Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide.
Article in Nature chemical biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
129 citing papers in PubMed, 1 synthesis or guideline pooled it, 238 citations in OpenAlex.
- Rejuvenation of Bone Marrow Mesenchymal Stem Cells: Mechanisms and Their Application in Senile Osteoporosis Treatment.Biomolecules · 2025Pooled it
- A novel fasting mimetic (Mimio) creates fasting-like benefits to hunger control, oxidative stress, and cardiometabolic health in humans.Scientific reports · 2026Trial
- Human fasting modulates macrophage function and upregulates multiple bioactive metabolites that extend lifespan in Caenorhabditis elegans: a pilot clinical study.The American journal of clinical nutrition · 2023Trial
- Trial
- Lactate promotes longevity through redox-driven lipid remodeling inbioRxiv : the preprint server for biology · 2025Article
- Structure-based machine learning screening identifies natural product candidates as potential geroprotectors.Journal of cheminformatics · 2025Article
- The role of NADnpj metabolic health and disease · 2025Review
- Chromatin and epigenetics in aging biology.Genetics · 2025Review
- Article
- 1-methylnicotinamide modulates IL-10 secretion and voriconazole metabolism.Frontiers in immunology · 2025Article
- Acylspermidines are conserved mitochondrial sirtuin-dependent metabolites.Nature chemical biology · 2024Article
- Clinical features and multiomics profiles indicate coagulation and platelet dysfunction in COVID-19 viral sepsis.iScience · 2024Article
- Nicotinamide N-Methyltransferase (NNMT): A New Hope for Treating Aging and Age-Related Conditions.Metabolites · 2024Review
- Piceatannol Upregulates SIRT1 Expression in Skeletal Muscle Cells and in Human Whole Blood: In Vitro Assay and a Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Comparison Trial.Life (Basel, Switzerland) · 2024Article
- Trigonelline is an NADNature metabolism · 2024Article
- The African killifish: A short-lived vertebrate model to study the biology of sarcopenia and longevity.Aging cell · 2024Article
- Extracellular Matrix Dynamics as an Emerging yet Understudied Hallmark of Aging and Longevity.Aging and disease · 2023Review
- Decreased SIRT1 Activity Is Involved in the Acute Injury Response of Chondrocytes to Ex Vivo Injurious Mechanical Overload.International journal of molecular sciences · 2023Article
- The Central Role of the NAD+ Molecule in the Development of Aging and the Prevention of Chronic Age-Related Diseases: Strategies for NAD+ Modulation.International journal of molecular sciences · 2023Review
- Review
69 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 11 institutions in 4 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.