Affinage

SIRT1

NAD-dependent protein deacetylase sirtuin-1 · UniProt Q96EB6

Length
747 aa
Mass
81.7 kDa
Annotated
2026-06-10
100 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SIRT1 is an NAD+-dependent protein deacetylase that functions as a central metabolic and stress sensor, coupling cellular energy status to the post-translational control of a broad set of histone and non-histone substrates (PMID:19262508). Its activity is set upstream by NAD+ availability—raised by AMPK to drive deacetylation of the metabolic regulators PGC-1α, FOXO1, and FOXO3a (PMID:19262508)—and by cyclin B/CDK1-mediated phosphorylation at T530/S540, which is required for normal cell cycle progression (PMID:19107194). Through substrate deacetylation, SIRT1 tunes energy metabolism and mitochondrial oxidative phosphorylation via PGC-1α (PMID:19262508, PMID:31180336), regulates nuclear receptor and vascular signaling by deacetylating LXR to activate ABCA1-dependent cholesterol transport (PMID:17936707) and eNOS to enhance NO production downstream of shear-stress/AMPK priming (PMID:20479254), and shapes immune and inflammatory programs by deacetylating RORγt to promote Th17 differentiation (PMID:25918343) and by restraining NF-κB/FOXO/NOX4-driven muscle wasting (PMID:32441762). A recurring mechanistic theme is SIRT1 control of protein stability: deacetylation blocks degradation of XRCC1 and p62 by preventing β-TrCP- and Keap1-mediated ubiquitination (PMID:31043584, PMID:33854041), while promoting degradation of p21 and STAT3 to drive proliferation (PMID:31201813, PMID:31881009). In cell cycle and DNA-damage control SIRT1 acts upstream of the checkpoint machinery, deacetylating and suppressing CHK2 and WEE1—epistasis with Chk2 rescues Sirt1-null neonatal lethality—and deacetylating Ku70 to support DNA double-strand break repair (PMID:17334224, PMID:31209362, PMID:36635566). SIRT1 itself is removed during senescence and aging through a direct SIRT1–LC3 interaction that targets nuclear SIRT1 for autophagosomal–lysosomal degradation (PMID:32989246).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2007 High

    Established SIRT1 as a deacetylase of non-histone signaling substrates by showing it directly deacetylates LXR nuclear receptors and the DNA-repair factor Ku70, extending its role beyond chromatin.

    Evidence Co-IP, in vitro deacetylation assays, site-directed mutagenesis (LXRα K432), dominant-negative SIRT1, and DNA strand-break repair assays

    PMID:17334224 PMID:17936707

    Open questions at the time
    • Direct enzymatic requirement for Ku70 deacetylation shown only with dominant-negative SIRT1, not site-mapped acetyl-lysine
    • Physiological NAD+ dependence of LXR/Ku70 deacetylation not addressed in these studies
  2. 2008 High

    Resolved how SIRT1 catalytic activity is regulated post-translationally, identifying multisite phosphorylation and CDK1 as a direct kinase controlling its deacetylase activity and cell-cycle function.

    Evidence Mass spectrometry of 13 phosphosites, phosphatase treatment with deacetylase activity assay, cyclin B/CDK1 Co-IP, and T530/S540 mutagenesis with cell-cycle readout

    PMID:19107194

    Open questions at the time
    • Structural basis for how phosphorylation modulates catalysis not defined
    • Functions of the remaining phosphosites beyond T530/S540 unresolved
  3. 2009 High

    Placed SIRT1 within an upstream metabolic-sensing circuit by showing AMPK raises NAD+ to activate SIRT1-dependent deacetylation of PGC-1α and FOXOs, coordinating energy-metabolism gene expression.

    Evidence Biochemical NAD+ measurement, in vivo mouse skeletal muscle studies, and deacetylation assays of multiple substrates

    PMID:19262508

    Open questions at the time
    • Quantitative contribution of NAD+ flux versus other inputs to SIRT1 activation not partitioned
    • Tissue-specific differences in the AMPK–NAD+–SIRT1 axis not mapped
  4. 2010 High

    Extended SIRT1 into vascular and adipogenic contexts, showing AMPK-primed phosphorylation of eNOS enables SIRT1 deacetylation and NO production, and that C/EBPα transcriptionally induces SIRT1 during adipogenesis.

    Evidence Co-IP, eNOS phospho-site mutants, AMPKα2-/- mice (eNOS); promoter deletion, EMSA, ChIP, and C/EBPα gain/loss of function (SIRT1 expression)

    PMID:20157332 PMID:20479254

    Open questions at the time
    • C/EBPα–SIRT1 regulation is Medium-confidence and from a single lab
    • Crosstalk between transcriptional SIRT1 induction and post-translational activation not integrated
  5. 2015 High

    Defined a substrate-level mechanism linking SIRT1 to adaptive immunity by showing deacetylation of RORγt enhances Th17 differentiation and autoimmune disease in vivo.

    Evidence Co-IP, deacetylation assay, T-cell-specific Sirt1 knockout mice, hematopoietic chimeras, and EAE model

    PMID:25918343

    Open questions at the time
    • RORγt acetyl-lysine site not specified
    • Relationship to other SIRT1 immune substrates (e.g. NF-κB) not reconciled
  6. 2019 High

    Positioned SIRT1 upstream of the DNA-damage checkpoint and protein-stability control, showing it deacetylates CHK2 (K520) to restrain its activation, deacetylates XRCC1 to block β-TrCP-dependent degradation, and destabilizes STAT3 and p21 to drive proliferation.

    Evidence Co-IP, in vitro deacetylation and ubiquitination assays, site mapping, Chk2/Sirt1 double-knockout epistasis, chemoresistance and proliferation assays in vitro and in vivo

    PMID:31043584 PMID:31201813 PMID:31209362 PMID:31881009

    Open questions at the time
    • Opposing effects of SIRT1 on substrate stability (stabilizing XRCC1/p62 vs destabilizing p21/STAT3) lack a unifying determinant
    • STAT3 and p21 findings are Medium-confidence single-lab studies
  7. 2019 High

    Connected SIRT1 substrate deacetylation to disease metabolism, showing PGC-1α-dependent oxidative phosphorylation in CML leukemia stem cells and NF-κB/FOXO/NOX4-driven oxidative muscle wasting upon SIRT1 loss.

    Evidence Conditional Sirt1 deletion in CML and tumor-bearing mice, mitochondrial respiration assays, RNA-seq, Nox4 muscle-specific knockout, and genetic/pharmacological rescue

    PMID:31180336 PMID:32441762

    Open questions at the time
    • Direct acetylation targets within the NF-κB/FOXO/NOX4 axis not fully resolved
    • Whether mitochondrial and inflammatory phenotypes share common SIRT1 substrates unaddressed
  8. 2020 High

    Revealed how SIRT1 protein levels decline with age, identifying nuclear SIRT1 as a direct LC3-bound autophagy substrate that is shuttled to the cytoplasm and degraded during senescence.

    Evidence SIRT1-LC3 Co-IP, live-cell imaging of nucleo-cytoplasmic shuttling, lysosomal inhibitors, and validation in aged mouse tissues and human CD8+CD28- T cells

    PMID:32989246

    Open questions at the time
    • Signal that designates nuclear SIRT1 for LC3 recognition not defined
    • Whether catalytic activity or modification state gates autophagic targeting unknown
  9. 2021 High

    Broadened SIRT1's substrate range to hypoxia and selective autophagy, showing deacetylation of HIF-2α limits renal fibrosis and deacetylation of p62 (K295) blocks Keap1-mediated degradation to influence liver tumorigenesis.

    Evidence Co-IP, deacetylation and ubiquitination assays, conditional Sirt1 knockout mice, Hif2a epistasis, and DEN carcinogenesis with p62 rescue

    PMID:33758176 PMID:33854041

    Open questions at the time
    • HIF-2α acetyl-lysine site not mapped
    • Context determining whether SIRT1 acts as tumor suppressor or promoter not resolved
  10. 2023 High

    Defined a phospho-acetyl switch on WEE1 controlled by SIRT1, showing CHK1-primed, GCN5-mediated K177 acetylation activates WEE1 while SIRT1 deacetylation maintains it inactive, with implications for WEE1-inhibitor resistance.

    Evidence Co-IP, in vitro deacetylation, K177 mutagenesis, kinase activity assays, and SIRT1 knockdown with WEE1-inhibitor sensitivity

    PMID:36635566

    Open questions at the time
    • In vivo relevance to tumor responses to WEE1 inhibition not established here
    • Interplay between SIRT1 control of CHK2 and WEE1 in the same checkpoint not integrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single deacetylase selects among its many competing substrates in a given cell state, and what determines whether deacetylation stabilizes or destabilizes a target, remains unresolved.
  • No unifying model for substrate selection across metabolic, checkpoint, and immune contexts
  • Determinants of opposing stability outcomes (XRCC1/p62 stabilized vs p21/STAT3 destabilized) not defined
  • Quantitative coupling between NAD+/phosphorylation inputs and substrate-specific output not measured

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 11 GO:0016787 hydrolase activity 5 GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 2 GO:0000228 nuclear chromosome 1 GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 5 R-HSA-1430728 Metabolism 4 R-HSA-73894 DNA Repair 3 R-HSA-168256 Immune System 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-9612973 Autophagy 2
Partners
CDK1CHK2FOXO1KU70LXRMAP1LC3PPARGC1AWEE1

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 AMPK enhances SIRT1 activity by increasing cellular NAD+ levels, resulting in SIRT1-mediated deacetylation of PGC-1α, FOXO1, and FOXO3a, thereby coordinating energy metabolism gene expression in skeletal muscle. Biochemical NAD+ measurement, in vivo mouse studies, deacetylation assays of downstream targets Nature High 19262508
2007 SIRT1 directly interacts with and deacetylates LXR nuclear receptors at a conserved lysine (K432 in LXRα, K433 in LXRβ), promoting subsequent LXR ubiquitination and activating LXR target genes including the cholesterol transporter ABCA1; mutation of K432 abolishes LXRα activation by SIRT1. Co-immunoprecipitation, in vitro deacetylation assay, site-directed mutagenesis, LXR target gene expression analysis in SIRT1-deficient cells Molecular cell High 17936707
2007 SIRT1 physically complexes with DNA repair protein Ku70 and deacetylates it; catalytically inactive dominant-negative SIRT1 fails to deacetylate Ku70 or enhance DNA repair capacity after radiation, establishing SIRT1's enzymatic activity as required for Ku70 deacetylation-dependent DNA repair. Co-immunoprecipitation, dominant-negative SIRT1 mutant, siRNA knockdown, DNA strand break repair assay Experimental & molecular medicine Medium 17334224
2008 SIRT1 is phosphorylated at 13 residues in vivo; dephosphorylation by phosphatases reduces NAD+-dependent deacetylase activity; cyclin B/CDK1 forms a complex with SIRT1 and phosphorylates it, with mutation of T530 and S540 (CDK1 sites) disturbing cell cycle progression and failing to rescue proliferation defects in SIRT1-deficient cells. Mass spectrometry identification of phosphorylation sites, in vitro phosphatase treatment with deacetylase activity assay, co-immunoprecipitation of cyclin B/CDK1 with SIRT1, site-directed mutagenesis PloS one High 19107194
2010 Laminar shear stress increases SIRT1 association with eNOS and promotes SIRT1-mediated deacetylation of eNOS; AMPK phosphorylation of eNOS at Ser-633/Ser-1177 is required to prime SIRT1-induced eNOS deacetylation and enhance NO production; AMPKα2-/- mice show elevated eNOS acetylation. Co-immunoprecipitation, eNOS phosphorylation-site mutants, AMPK inhibitor, in vivo AMPKα2 knockout mouse acetylation analysis Proceedings of the National Academy of Sciences of the United States of America High 20479254
2015 SIRT1 deacetylates RORγt, the signature transcription factor of Th17 cells, increasing RORγt transcriptional activity and enhancing Th17 cell generation and function; T cell-specific Sirt1 deletion and pharmacological SIRT1 inhibition suppress Th17 differentiation and are protective in a mouse model of multiple sclerosis. SIRT1-RORγt co-immunoprecipitation, deacetylation assay, T cell-specific Sirt1 knockout mice, mixed hematopoietic chimeras, EAE mouse model The Journal of experimental medicine High 25918343
2019 SIRT1 interacts with CHK2 and deacetylates it at K520, suppressing CHK2 phosphorylation, dimerization, and activation; SIRT1 depletion induces CHK2 hyperactivation-mediated cell cycle arrest; genetic deletion of Chk2 rescues the neonatal lethality of Sirt1-/- mice, placing SIRT1 upstream of CHK2 in cell cycle control. Co-immunoprecipitation, deacetylation assay, CHK2 phosphorylation/dimerization analysis, siRNA/genetic KO, epistasis via Chk2/Sirt1 double-knockout mice Cell death and differentiation High 31209362
2019 SIRT1 binds and deacetylates XRCC1 at K260, K298, and K431, preventing β-TrCP-dependent ubiquitination and proteasomal degradation of XRCC1; mutations at these lysines abrogate β-TrCP interaction and prolong XRCC1 half-life; SIRT1 knockdown reverses chemoresistance by enhancing XRCC1 degradation. Co-immunoprecipitation, in vitro deacetylation assay, site-directed mutagenesis, ubiquitination assay, siRNA knockdown, chemoresistance functional assay Cell death & disease High 31043584
2020 During cellular senescence, nuclear SIRT1 is recognized as an autophagy substrate via a direct SIRT1-LC3 interaction, shuttled from nucleus to cytoplasm, and degraded through the autophagosome-lysosome pathway; this mechanism also operates in vivo during aging of hematopoietic and immune organs in mice and in aged human CD8+CD28- T cells. Nuclear autophagy substrate identification, SIRT1-LC3 co-immunoprecipitation, live-cell imaging of nucleus-to-cytoplasm shuttling, lysosomal inhibitor experiments, in vivo mouse aging tissues and human aged T cell analysis Nature cell biology High 32989246
2021 SIRT1 directly interacts with and deacetylates HIF-2α; conditional knockout of Sirt1 in renal interstitial cells increases HIF-2α expression and exacerbates renal fibrosis in UUO mice; pharmacological SIRT1 activation decreases HIF-2α and fibrotic gene expression in cultured renal cells. Co-immunoprecipitation, deacetylation assay, conditional Sirt1 knockout mice, Hif2a knockout epistasis, in vitro SIRT1 activator/inhibitor treatment Cell death discovery High 33758176
2021 SIRT1 deacetylates p62 at K295, preventing Keap1-mediated poly-ubiquitination and proteasomal degradation of p62; acetylated p62 increases its interaction with E3 ligase Keap1; hepatocyte-specific Sirt1 knockout mice develop fewer liver tumors after DEN treatment, reversed by exogenous p62 re-introduction. Co-immunoprecipitation, deacetylation assay at K295, ubiquitination assay, hepatocyte-specific Sirt1 conditional KO mice, DEN carcinogenesis model, p62 rescue experiment Cell death & disease High 33854041
2023 SIRT1 associates with and deacetylates WEE1 kinase, maintaining it in an inactive state; SIRT1 deficiency induces WEE1 hyperacetylation at K177 and activation, rendering cancer cells resistant to WEE1 inhibition; CHK1-dependent phosphorylation of WEE1 at S642 primes GCN5-mediated acetylation at K177 which activates WEE1, counteracted by SIRT1. Co-immunoprecipitation, in vitro deacetylation assay, site-directed mutagenesis at K177, kinase activity assay, SIRT1 knockdown, genetic loss-of-function with WEE1 inhibitor sensitivity Nature chemical biology High 36635566
2019 SIRT1 loss in skeletal muscle activates NF-κB signaling, which enhances FOXO transcription factor expression and NADPH oxidase 4 (NOX4) expression, driving reactive oxygen species production and cancer cachexia; rescuing SIRT1 expression or knocking out Nox4 abrogates tumor-induced muscle wasting in mice. RNA-seq, exogenous SIRT1 expression rescue, pharmacological SIRT1 activator, Nox4 muscle-specific knockout mice, in vitro myotube wasting assay, tumor-bearing mouse model The Journal of experimental medicine High 32441762
2019 SIRT1 deletion in CML mice reduces mitochondrial oxidative phosphorylation in leukemia stem cells (LSCs); the SIRT1 substrate PGC-1α contributes to increased oxidative phosphorylation and TKI resistance in CML LSCs; mitochondrial alterations are BCR-ABL kinase-independent. Conditional Sirt1 deletion in transgenic CML mice, mitochondrial respiration measurement, PGC-1α substrate analysis, TKI treatment of SIRT1-deleted mice The Journal of clinical investigation High 31180336
2011 SIRT1 inhibition blocks FoxO1-dependent DNA repair (GADD45α expression) in β-cells exposed to nitric oxide, and shifts FoxO1 toward a proapoptotic program including PUMA mRNA accumulation and caspase-3 cleavage; FoxO1 nuclear translocation and transcriptional activation in response to nitric oxide is regulated by SIRT1. SIRT1 pharmacological inhibitors, FoxO1 subcellular localization tracking, GADD45α and PUMA mRNA measurement, caspase-3 cleavage assay, DNA repair assay The Journal of biological chemistry Medium 21196578
2017 SIRT1 binds in the β-globin gene cluster locus control region (LCR) and HBG promoters, promotes LCR looping to the HBG promoter, and increases RNA polymerase II and H4K16Ac binding at HBG promoter; SIRT1 suppresses expression of HBG suppressors BCL11A, KLF1, HDAC1, and HDAC2 to activate fetal hemoglobin (γ-globin) gene expression. ChIP for SIRT1 at LCR and HBG promoters, chromosome conformation/looping assay, SIRT1 knockdown/ectopic expression, small molecule SIRT1 activators, RNA polymerase II ChIP American journal of hematology Medium 28776729
2017 SIRT1 positively affects macrophage self-renewal by regulating G1/S cell cycle transition; SIRT1 inhibition activates FOXO1 and suppresses E2F1 and Myc (known SIRT1 targets mediating cell cycle progression), restricting macrophage proliferation both in vitro and in vivo. SIRT1 overexpression/shRNA knockdown/CRISPR-Cas9 deletion, pharmacological inhibition, in vivo alveolar and peritoneal macrophage proliferation assay, cell cycle analysis The EMBO journal Medium 28701484
2019 SIRT1 deacetylates STAT3, leading to STAT3 destabilization and degradation, thereby reducing FGB expression and inhibiting renal cell carcinoma (RCC) proliferation; co-immunoprecipitation confirmed SIRT1-STAT3 physical interaction. Co-immunoprecipitation, Western blot for STAT3 protein stability, SIRT1 overexpression, luciferase reporter for FGB as STAT3 target, in vitro and in vivo proliferation assays Experimental cell research Medium 31201813
2019 SIRT1 deacetylates p21, promoting p21 ubiquitination and degradation, thereby inducing cardiomyocyte proliferation; overexpression of SIRT1 increases EdU-, pH3-, and Aurora B-positive cardiomyocytes in neonatal and adult mice; depletion of SIRT1 reduces cardiomyocyte proliferation in vitro and in vivo. Deacetylation assay, ubiquitination assay, SIRT1 overexpression/knockdown, EdU/pH3/Aurora B proliferation markers in vitro and in vivo in mouse hearts Aging Medium 31881009
2010 C/EBPα directly binds to the SIRT1 promoter at a consensus C/EBPα binding site and upregulates SIRT1 mRNA and protein expression during adipogenesis; knockdown of C/EBPα decreases SIRT1 protein levels in preadipocytes. Promoter deletion analysis, gel shift assay (EMSA), chromatin immunoprecipitation (ChIP), C/EBPα ectopic expression and siRNA knockdown, luciferase reporter assay Cell research Medium 20157332
2016 SIRT1 promotes ABCG2 expression in the ileum via deacetylation of PGC-1α, which then activates PPARγ effectors; siRNA blockade of PGC-1α or PPARγ significantly inhibits SIRT1-induced ABCG2 upregulation, demonstrating the PGC-1α/PPARγ-ABCG2 pathway downstream of SIRT1 in uric acid regulation. siRNA knockdown of PGC-1α and PPARγ, PGC-1α deacetylation assay, in vivo hyperuricemia mouse model with resveratrol treatment, ABCG2 expression analysis Endocrine Medium 27022940
2021 SIRT1 interacts with ADNP at two sites: one at the microtubule end-binding protein (EB1/EB3)/Tau level and one on chromatin, where ADNP, YY1, and HDAC2 share a DNA-binding motif that regulates SIRT1, ADNP, and EB1 expression; this ADNP-SIRT1 complex is linked to sex- and age-dependent histone modification via WDR5. Co-immunoprecipitation of ADNP-SIRT1 complex, single-cell RNA and protein expression analysis, gene expression correlation in mouse/human brain, chromatin binding motif analysis Molecular psychiatry Low 33967268

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature 2699 19262508
2013 SIRT1 and other sirtuins in metabolism. Trends in endocrinology and metabolism: TEM 941 24388149
2010 AMPK and SIRT1: a long-standing partnership? American journal of physiology. Endocrinology and metabolism 743 20103737
2016 Sirt1 and the Mitochondria. Molecules and cells 602 26831453
2022 Regulation of SIRT1 and Its Roles in Inflammation. Frontiers in immunology 588 35359990
2020 SIRT1 and aging related signaling pathways. Mechanisms of ageing and development 541 32084459
2007 SIRT1 deacetylates and positively regulates the nuclear receptor LXR. Molecular cell 530 17936707
2010 Regulation of SIRT1 in cellular functions: role of polyphenols. Archives of biochemistry and biophysics 516 20450879
2020 SIRT1 is downregulated by autophagy in senescence and ageing. Nature cell biology 390 32989246
2008 How does SIRT1 affect metabolism, senescence and cancer? Nature reviews. Cancer 375 19132007
2013 SIRT1 and SIRT2: emerging targets in neurodegeneration. EMBO molecular medicine 336 23417962
2017 Emerging roles of SIRT1 in fatty liver diseases. International journal of biological sciences 292 28808418
2007 SIRT1 promotes DNA repair activity and deacetylation of Ku70. Experimental & molecular medicine 290 17334224
2009 SIRT1 and insulin resistance. Nature reviews. Endocrinology 289 19455179
2004 The interaction between FOXO and SIRT1: tipping the balance towards survival. Trends in cell biology 288 15308206
2009 SIRT1, is it a tumor promoter or tumor suppressor? International journal of biological sciences 282 19173036
2013 SIRT1 and energy metabolism. Acta biochimica et biophysica Sinica 279 23257294
2008 Phosphorylation regulates SIRT1 function. PloS one 230 19107194
2010 Shear stress, SIRT1, and vascular homeostasis. Proceedings of the National Academy of Sciences of the United States of America 223 20479254
2020 SIRT1 Activation by Natural Phytochemicals: An Overview. Frontiers in pharmacology 217 32848804
2012 Negative regulation of inflammation by SIRT1. Pharmacological research 206 23098819
2008 The ups and downs of SIRT1. Trends in biochemical sciences 201 18805010
2011 Protective roles of SIRT1 in atherosclerosis. Cell cycle (Georgetown, Tex.) 191 21293192
2012 MicroRNA Regulation of SIRT1. Frontiers in physiology 160 22479251
2006 SIRT1 and endocrine signaling. Trends in endocrinology and metabolism: TEM 143 16684606
2021 SIRT1 and SIRT2 Activity Control in Neurodegenerative Diseases. Frontiers in pharmacology 136 33597872
2016 Sirt1: Role Under the Condition of Ischemia/Hypoxia. Cellular and molecular neurobiology 129 26971525
2015 SIRT1 deacetylates RORγt and enhances Th17 cell generation. The Journal of experimental medicine 129 25918343
2008 Sirt1 deficiency attenuates spermatogenesis and germ cell function. PloS one 128 18270565
2013 The ways and means that fine tune Sirt1 activity. Trends in biochemical sciences 127 23394938
2021 Interplay between oxidative stress, SIRT1, reproductive and metabolic functions. Current research in physiology 118 34746831
2009 Biochemical effects of SIRT1 activators. Biochimica et biophysica acta 117 19897059
2015 SIRT1 and insulin resistance. Journal of diabetes and its complications 116 26422395
2012 Perspectives on translational and therapeutic aspects of SIRT1 in inflammaging and senescence. Biochemical pharmacology 111 22796566
2008 A review of Sirt1 and Sirt1 modulators in cardiovascular and metabolic diseases. Recent patents on cardiovascular drug discovery 105 18991791
2017 SIRT1 regulates macrophage self-renewal. The EMBO journal 102 28701484
2017 The role of SIRT1 in diabetic retinopathy. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 101 29091865
2012 Targeting cardiovascular disease with novel SIRT1 pathways. Future cardiology 100 22185448
2015 Multifaceted Modulation of SIRT1 in Cancer and Inflammation. Critical reviews in oncogenesis 98 25746104
2021 SIRT1-FOXOs activity regulates diabetic complications. Pharmacological research 94 34856334
2010 Controlling SIRT1 expression by microRNAs in health and metabolic disease. Aging 91 20689156
2012 SIRT1, metabolism and cancer. Current opinion in oncology 90 22080944
2018 Role and Possible Mechanisms of Sirt1 in Depression. Oxidative medicine and cellular longevity 89 29643977
2007 SIRT1 and neuronal diseases. Molecular aspects of medicine 88 17397914
2020 SIRT1 - a new mammalian substrate of nuclear autophagy. Autophagy 84 33292048
2018 Sirt1 Antisense Long Noncoding RNA Promotes Cardiomyocyte Proliferation by Enhancing the Stability of Sirt1. Journal of the American Heart Association 83 30608184
2009 Metabolic benefits from Sirt1 and Sirt1 activators. Current opinion in clinical nutrition and metabolic care 83 19474719
2014 The Role of SIRT1 in Diabetic Kidney Disease. Frontiers in endocrinology 81 25346724
2020 SIRT1 Antagonizes Oxidative Stress in Diabetic Vascular Complication. Frontiers in endocrinology 77 33304318
2020 SIRT1 Regulation in Ageing and Obesity. Mechanisms of ageing and development 74 32320732
2014 P53 and Sirt1: routes of metabolism and genome stability. Biochemical pharmacology 74 25218422
2023 SIRT1/SREBPs-mediated regulation of lipid metabolism. Pharmacological research 73 38070792
2019 SIRT1 modulates cell cycle progression by regulating CHK2 acetylation-phosphorylation. Cell death and differentiation 73 31209362
2011 Expression and role of SIRT1 in hepatocellular carcinoma. Oncology reports 72 21567102
2013 Regulation of SIRT1 by microRNAs. Molecules and cells 71 24213676
2008 SIRT1: roles in aging and cancer. BMB reports 70 19017485
2017 The NAD+/PARP1/SIRT1 Axis in Aging. Rejuvenation research 68 28537485
2021 SIRT1, a promising regulator of bone homeostasis. Life sciences 66 33453243
2020 SIRT1-NOX4 signaling axis regulates cancer cachexia. The Journal of experimental medicine 62 32441762
2011 FoxO1 and SIRT1 regulate beta-cell responses to nitric oxide. The Journal of biological chemistry 62 21196578
2019 P53/NRF2 mediates SIRT1's protective effect on diabetic nephropathy. Biochimica et biophysica acta. Molecular cell research 61 30959066
2022 SIRT1 and Autophagy: Implications in Endocrine Disorders. Frontiers in endocrinology 60 35909524
2019 SIRT1 regulates metabolism and leukemogenic potential in CML stem cells. The Journal of clinical investigation 60 31180336
2015 Sirt1 in cerebral ischemia. Brain circulation 60 26819971
2010 C/EBPalpha regulates SIRT1 expression during adipogenesis. Cell research 58 20157332
2021 Trending topics of SIRT1 in tumorigenicity. Biochimica et biophysica acta. General subjects 57 34147543
2024 SIRT1, resveratrol and aging. Frontiers in genetics 56 38784035
2022 Nutraceutical activation of Sirt1: a review. Open heart 54 36522127
2015 Role of SIRT1 in autoimmune demyelination and neurodegeneration. Immunologic research 54 25281273
2024 SIRT1: Harnessing multiple pathways to hinder NAFLD. Pharmacological research 53 38527697
2022 Resveratrol-like Compounds as SIRT1 Activators. International journal of molecular sciences 52 36499460
2019 SIRT1 deacetylated and stabilized XRCC1 to promote chemoresistance in lung cancer. Cell death & disease 51 31043584
2021 SIRT1 attenuates renal fibrosis by repressing HIF-2α. Cell death discovery 50 33758176
2012 Sirt1: def-eating senescence? Cell cycle (Georgetown, Tex.) 49 22983125
2023 The Role of Sirtuin 1 (SIRT1) in Neurodegeneration. Cureus 47 37456463
2016 SIRT1 prevents hyperuricemia via the PGC-1α/PPARγ-ABCG2 pathway. Endocrine 47 27022940
2009 Cellular regulation of SIRT1. Current pharmaceutical design 46 19149601
2021 Sirt1 deacetylates and stabilizes p62 to promote hepato-carcinogenesis. Cell death & disease 43 33854041
2021 Introducing ADNP and SIRT1 as new partners regulating microtubules and histone methylation. Molecular psychiatry 43 33967268
2013 Cross-talk between SIRT1 and p66Shc in vascular diseases. Trends in cardiovascular medicine 42 23499302
2015 SIRT1 and Kidney Function. Kidney diseases (Basel, Switzerland) 41 27536685
2013 Towards elucidating the role of SirT1 in osteoarthritis. Frontiers in bioscience (Landmark edition) 39 23276927
2012 Metabolic actions of hypothalamic SIRT1. Trends in endocrinology and metabolism: TEM 39 22382036
2017 SIRT1 activates the expression of fetal hemoglobin genes. American journal of hematology 38 28776729
2020 Impact of circadian disruption on health; SIRT1 and Telomeres. DNA repair 37 33038659
2017 Resveratrol Attenuates Microglial Activation via SIRT1-SOCS1 Pathway. Evidence-based complementary and alternative medicine : eCAM 37 28781601
2010 Sirt1's systemic protective roles and its promise as a target in antiaging medicine. Translational research : the journal of laboratory and clinical medicine 37 21497775
2017 The Role of Sirt1 in Epileptogenesis. eNeuro 36 28197553
2022 Irisin enhances longevity by boosting SIRT1, AMPK, autophagy and telomerase. Expert reviews in molecular medicine 35 36503597
2019 SIRT1 downregulated FGB expression to inhibit RCC tumorigenesis by destabilizing STAT3. Experimental cell research 35 31201813
2019 Sirt1-inducible deacetylation of p21 promotes cardiomyocyte proliferation. Aging 35 31881009
2015 Expression of SIRT1 and SIRT3 varies according to age in mice. Anatomy & cell biology 35 25806122
2013 Roles of SIRT1 in leukemogenesis. Current opinion in hematology 35 23519155
2009 Physiological and pathophysiological functions of SIRT1. Mini reviews in medicinal chemistry 34 19275731
2014 Linking DNA damage, NAD(+)/SIRT1, and aging. Cell metabolism 33 25440052
2023 Naringenin ameliorates vascular senescence and atherosclerosis involving SIRT1 activation. The Journal of pharmacy and pharmacology 32 37343148
2021 SIRT1 and gynecological malignancies (Review). Oncology reports 32 33649834
2018 AHR Regulates Metabolic Reprogramming to Promote SIRT1-Dependent Keratinocyte Differentiation. The Journal of investigative dermatology 31 30393078
2023 SIRT1 deacetylates WEE1 and sensitizes cancer cells to WEE1 inhibition. Nature chemical biology 30 36635566
2016 Epigenetic Regulation Through SIRT1 in Podocytes. Current hypertension reviews 30 26931472

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