HCSGD entry for SIRT1

1. General information

Official gene symbol	SIRT1
Entrez ID	23411
Gene full name	sirtuin 1
Other gene symbols	SIR2L1
Links to Entrez Gene	Links to Entrez Gene

2. Neighbors in the network

3. Gene ontology annotation

GO ID	GO term	Evidence	Category
GO:0000012	Single strand break repair	IMP	biological_process
GO:0000122	Negative regulation of transcription from RNA polymerase II promoter	IDA IMP	biological_process
GO:0000183	Chromatin silencing at rDNA	IDA	biological_process
GO:0000720	Pyrimidine dimer repair by nucleotide-excision repair	IEA IMP	biological_process
GO:0000731	DNA synthesis involved in DNA repair	IEA ISS	biological_process
GO:0000790	Nuclear chromatin	IDA	cellular_component
GO:0001525	Angiogenesis	IDA	biological_process
GO:0001542	Ovulation from ovarian follicle	IEA	biological_process
GO:0001678	Cellular glucose homeostasis	IEA ISS	biological_process
GO:0001934	Positive regulation of protein phosphorylation	ISS	biological_process
GO:0002039	P53 binding	IEA IPI	molecular_function
GO:0002821	Positive regulation of adaptive immune response	IDA	biological_process
GO:0003714	Transcription corepressor activity	IDA IEA ISS	molecular_function
GO:0003950	NAD+ ADP-ribosyltransferase activity	TAS	molecular_function
GO:0004407	Histone deacetylase activity	IDA	molecular_function
GO:0005515	Protein binding	IPI	molecular_function
GO:0005634	Nucleus	IDA	cellular_component
GO:0005635	Nuclear envelope	IDA	cellular_component
GO:0005637	Nuclear inner membrane	IDA	cellular_component
GO:0005654	Nucleoplasm	IDA	cellular_component
GO:0005677	Chromatin silencing complex	IDA	cellular_component
GO:0005719	Nuclear euchromatin	IDA	cellular_component
GO:0005720	Nuclear heterochromatin	IDA IEA	cellular_component
GO:0005730	Nucleolus	IDA	cellular_component
GO:0005737	Cytoplasm	IDA	cellular_component
GO:0006260	DNA replication	TAS	biological_process
GO:0006281	DNA repair	TAS	biological_process
GO:0006342	Chromatin silencing	TAS	biological_process
GO:0006343	Establishment of chromatin silencing	IDA	biological_process
GO:0006344	Maintenance of chromatin silencing	IMP	biological_process
GO:0006346	Methylation-dependent chromatin silencing	TAS	biological_process
GO:0006351	Transcription, DNA-templated	IEA	biological_process
GO:0006364	RRNA processing	IEA	biological_process
GO:0006471	Protein ADP-ribosylation	TAS	biological_process
GO:0006476	Protein deacetylation	IDA IMP	biological_process
GO:0006642	Triglyceride mobilization	IEA ISS	biological_process
GO:0006974	Cellular response to DNA damage stimulus	IDA	biological_process
GO:0006979	Response to oxidative stress	IDA	biological_process
GO:0007283	Spermatogenesis	IEA	biological_process
GO:0007346	Regulation of mitotic cell cycle	IDA	biological_process
GO:0007517	Muscle organ development	IEA	biological_process
GO:0007569	Cell aging	TAS	biological_process
GO:0008022	Protein C-terminus binding	IPI	molecular_function
GO:0008284	Positive regulation of cell proliferation	IMP	biological_process
GO:0008630	Intrinsic apoptotic signaling pathway in response to DNA damage	IEA	biological_process
GO:0009267	Cellular response to starvation	IEA ISS	biological_process
GO:0010875	Positive regulation of cholesterol efflux	IEA ISS	biological_process
GO:0010906	Regulation of glucose metabolic process	IEA ISS	biological_process
GO:0016032	Viral process	IEA	biological_process
GO:0016239	Positive regulation of macroautophagy	IDA IEA	biological_process
GO:0016567	Protein ubiquitination	IDA	biological_process
GO:0016575	Histone deacetylation	IDA	biological_process
GO:0016605	PML body	IDA	cellular_component
GO:0017136	NAD-dependent histone deacetylase activity	IDA	molecular_function
GO:0018394	Peptidyl-lysine acetylation	IMP	biological_process
GO:0019213	Deacetylase activity	IDA	molecular_function
GO:0019899	Enzyme binding	IEA	molecular_function
GO:0019904	Protein domain specific binding	IEA	molecular_function
GO:0030308	Negative regulation of cell growth	IMP	biological_process
GO:0030512	Negative regulation of transforming growth factor beta receptor signaling pathway	IEA ISS	biological_process
GO:0031393	Negative regulation of prostaglandin biosynthetic process	IEA ISS	biological_process
GO:0031648	Protein destabilization	IEA ISS	biological_process
GO:0031937	Positive regulation of chromatin silencing	IMP	biological_process
GO:0032007	Negative regulation of TOR signaling	IEA IMP	biological_process
GO:0032071	Regulation of endodeoxyribonuclease activity	IMP	biological_process
GO:0032088	Negative regulation of NF-kappaB transcription factor activity	IDA	biological_process
GO:0032868	Response to insulin	IEA ISS	biological_process
GO:0033158	Regulation of protein import into nucleus, translocation	IMP	biological_process
GO:0033553	RDNA heterochromatin	IDA	cellular_component
GO:0033558	Protein deacetylase activity	IDA	molecular_function
GO:0034391	Regulation of smooth muscle cell apoptotic process	IEA ISS	biological_process
GO:0034979	NAD-dependent protein deacetylase activity	IDA IMP	molecular_function
GO:0034983	Peptidyl-lysine deacetylation	IDA	biological_process
GO:0035098	ESC/E(Z) complex	IDA	cellular_component
GO:0035356	Cellular triglyceride homeostasis	IEA ISS	biological_process
GO:0035358	Regulation of peroxisome proliferator activated receptor signaling pathway	IEA ISS	biological_process
GO:0042127	Regulation of cell proliferation	IMP	biological_process
GO:0042326	Negative regulation of phosphorylation	IEA IMP	biological_process
GO:0042393	Histone binding	IPI	molecular_function
GO:0042542	Response to hydrogen peroxide	IDA	biological_process
GO:0042632	Cholesterol homeostasis	IEA ISS	biological_process
GO:0042771	Intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	IMP	biological_process
GO:0042802	Identical protein binding	IPI	molecular_function
GO:0043065	Positive regulation of apoptotic process	IDA IMP	biological_process
GO:0043066	Negative regulation of apoptotic process	IMP	biological_process
GO:0043124	Negative regulation of I-kappaB kinase/NF-kappaB signaling	IDA	biological_process
GO:0043161	Proteasome-mediated ubiquitin-dependent protein catabolic process	IMP	biological_process
GO:0043280	Positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	IMP	biological_process
GO:0043398	HLH domain binding	IPI	molecular_function
GO:0043425	BHLH transcription factor binding	IPI	molecular_function
GO:0043433	Negative regulation of sequence-specific DNA binding transcription factor activity	IDA IMP	biological_process
GO:0043518	Negative regulation of DNA damage response, signal transduction by p53 class mediator	IDA	biological_process
GO:0045348	Positive regulation of MHC class II biosynthetic process	IDA	biological_process
GO:0045599	Negative regulation of fat cell differentiation	IEA ISS	biological_process
GO:0045739	Positive regulation of DNA repair	IMP	biological_process
GO:0045892	Negative regulation of transcription, DNA-templated	IDA IEA	biological_process
GO:0045944	Positive regulation of transcription from RNA polymerase II promoter	IDA	biological_process
GO:0046628	Positive regulation of insulin receptor signaling pathway	IDA	biological_process
GO:0046872	Metal ion binding	IEA	molecular_function
GO:0046969	NAD-dependent histone deacetylase activity (H3-K9 specific)	IEA ISS	molecular_function
GO:0050872	White fat cell differentiation	IEA ISS	biological_process
GO:0051019	Mitogen-activated protein kinase binding	IPI	molecular_function
GO:0051097	Negative regulation of helicase activity	IDA	biological_process
GO:0051898	Negative regulation of protein kinase B signaling	IEA IMP	biological_process
GO:0055089	Fatty acid homeostasis	IEA ISS	biological_process
GO:0060766	Negative regulation of androgen receptor signaling pathway	IMP	biological_process
GO:0070301	Cellular response to hydrogen peroxide	IDA	biological_process
GO:0070403	NAD+ binding	IEA	molecular_function
GO:0070857	Regulation of bile acid biosynthetic process	IEA ISS	biological_process
GO:0070932	Histone H3 deacetylation	IDA IMP	biological_process
GO:0071356	Cellular response to tumor necrosis factor	IDA	biological_process
GO:0071456	Cellular response to hypoxia	IMP	biological_process
GO:0071479	Cellular response to ionizing radiation	IEA ISS	biological_process
GO:1902166	Negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	IEA ISS	biological_process
GO:1902176	Negative regulation of intrinsic apoptotic signaling pathway in response to oxidative stress	IMP	biological_process
GO:2000111	Positive regulation of macrophage apoptotic process	IEA ISS	biological_process
GO:2000480	Negative regulation of cAMP-dependent protein kinase activity	IDA	biological_process
GO:2000481	Positive regulation of cAMP-dependent protein kinase activity	IEA IMP	biological_process
GO:2000655	Negative regulation of cellular response to testosterone stimulus	IMP	biological_process
GO:2000757	Negative regulation of peptidyl-lysine acetylation	IDA	biological_process
GO:2000773	Negative regulation of cellular senescence	IDA	biological_process
GO:2000774	Positive regulation of cellular senescence	IDA	biological_process

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4. Expression levels in datasets

Meta-analysis result

p-value up	p-value down	FDR up	FDR down
0.3028948102	0.0681798982	0.9999902473	0.4928853337

Individual experiment result
( "-" represent NA in the specific microarray platform )

Data source	Up or down	Log fold change
GSE11954	Down	-0.5456646340
GSE13712_SHEAR	Up	0.0114353046
GSE13712_STATIC	Down	-0.2654773035
GSE19018	Down	-0.3677809676
GSE19899_A1	Up	0.8058800757
GSE19899_A2	Down	-0.6195490135
PubMed_21979375_A1	Up	0.1153985747
PubMed_21979375_A2	Down	-0.5121285234
GSE35957	Up	0.1164145333
GSE36640	Down	-1.1219808163
GSE54402	Down	-0.0945212840
GSE9593	Down	-0.2775063370
GSE43922	Up	0.0246839631
GSE24585	Up	0.1156565732
GSE37065	Up	0.1066734679
GSE28863_A1	Up	0.6918728294
GSE28863_A2	Up	0.8114567708
GSE28863_A3	Down	-0.1382183933
GSE28863_A4	Up	0.1116443899
GSE48662	Down	-0.9803985350

5. Regulation relationships with compounds/drugs/microRNAs

Compounds

Not regulated by compounds

Drugs

Name	Drug	Accession number
SRT501	DB05073	-

MicroRNAs

mirTarBase

MiRNA_name	mirBase ID	miRTarBase ID	Experiment	Support type	References (Pubmed ID)
hsa-miR-217	MIMAT0000274	MIRT000144	Luciferase reporter assay//Western blot	Functional MTI	19786632
hsa-miR-132-3p	MIMAT0000426	MIRT000333	Luciferase reporter assay//Western blot	Functional MTI	19819989
hsa-miR-449b-5p	MIMAT0003327	MIRT006349	Luciferase reporter assay//Western blot	Functional MTI	21418558
hsa-miR-449a	MIMAT0001541	MIRT006348	Luciferase reporter assay//Western blot	Functional MTI	21418558
hsa-miR-181b-5p	MIMAT0000257	MIRT006272	Luciferase reporter assay	Functional MTI	22228303
hsa-miR-34a-5p	MIMAT0000255	MIRT002098	Western blot//qRT-PCR//Luciferase reporter assay	Functional MTI	18834855
hsa-miR-34a-5p	MIMAT0000255	MIRT002098	Western blot//Luciferase reporter assay//Northern blot	Functional MTI	18755897
hsa-miR-34a-5p	MIMAT0000255	MIRT002098	Luciferase reporter assay	Functional MTI	19461653
hsa-miR-34a-5p	MIMAT0000255	MIRT002098	Luciferase reporter assay//qRT-PCR//Western blot//Reporter assay;Western blot;qRT-PCR	Functional MTI	20185821
hsa-miR-34a-5p	MIMAT0000255	MIRT002098	Luciferase reporter assay//Western blot	Functional MTI	19221490
hsa-miR-34a-5p	MIMAT0000255	MIRT002098	Luciferase reporter assay//qRT-PCR//Western blot//Reporter assay;Western blot;qRT-PCR	Functional MTI	20627091
hsa-miR-34a-5p	MIMAT0000255	MIRT002098	Flow//Luciferase reporter assay//qRT-PCR//Western blot	Functional MTI	20470934
hsa-miR-216a-5p	MIMAT0000273	MIRT005018	Luciferase reporter assay//Western blot	Non-Functional MTI	19786632
hsa-miR-138-5p	MIMAT0000430	MIRT006271	Luciferase reporter assay	Functional MTI	22228303
hsa-miR-181a-5p	MIMAT0000256	MIRT006213	Immunoblot//Luciferase reporter assay//qRT-PCR	Functional MTI	22476949
hsa-miR-181a-5p	MIMAT0000256	MIRT006213	Luciferase reporter assay	Functional MTI	22228303
hsa-miR-181c-5p	MIMAT0000258	MIRT006878	In situ hybridization//Luciferase reporter assay	Functional MTI	21720722
hsa-miR-9-5p	MIMAT0000441	MIRT006892	In situ hybridization//Luciferase reporter assay	Functional MTI	21720722
hsa-miR-9-5p	MIMAT0000441	MIRT006892	Western blot;qRT-PCR	Functional MTI	20362537
hsa-miR-128-3p	MIMAT0000424	MIRT007324	Luciferase reporter assay	Functional MTI	23492773
hsa-miR-124-3p	MIMAT0000422	MIRT023069	qRT-PCR	Non-Functional MTI (Weak)	20362537
hsa-miR-215-5p	MIMAT0000272	MIRT024509	Microarray	Functional MTI (Weak)	19074876
hsa-miR-192-5p	MIMAT0000222	MIRT026849	Microarray	Functional MTI (Weak)	19074876
hsa-miR-331-3p	MIMAT0000760	MIRT043458	CLASH	Functional MTI (Weak)	23622248
hsa-let-7c-5p	MIMAT0000064	MIRT051790	CLASH	Functional MTI (Weak)	23622248
hsa-miR-199a-5p	MIMAT0000231	MIRT052646	qRT-PCR//Western blot	Functional MTI	23760629

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mirRecord

MicroRNA name	mirBase ID	Target site number	MiRNA mature ID	Test method inter	MiRNA regulation site	Reporter target site	Pubmed ID
hsa-miR-34a-5p	MIMAT0000255	1	hsa-miR-34a				18755897

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6. Text-mining results about the gene

Gene occurances in abstracts of cellular senescence-associated articles: 192 abstracts the gene occurs.

PubMed ID of the article	Sentenece the gene occurs
28096886	Cultured BMECs were treated with H2O2, STL, or nicotinamide (NAM, a SIRT1 inhibitor)
28096886	Expression of SIRT1, p21, and PGC-1alpha was determined by western blot
28096886	Further assays showed upregulation of SIRT1 and PGC-1alpha and downregulation of p21 after STL treatment
28096886	The results revealed that STL could protect BMECs against oxidative stress injury at least partially through the SIRT1 pathway
27354409	Mechanistic studies revealed that up-regulation of transcription factor DeltaNp63 led to the decline of miR-181a expression, resulting in an overexpression of the antiaging protein Sirt1, in CD4+ T cells from HCV-infected individuals
27354409	Either reconstituting miR-181a or silencing DeltaNp63 or Sirt1 expression in CD4+ T cells led to accelerated T cell senescence, as evidenced by an increased senescence-associated beta-galactosidase (SA-beta-gal) expression, shortened telomere length, and decreased EdU incorporation; this suggests that HCV-induced T cell senescence is counterregulated by the DeltaNp63-miR-181a-Sirt1 pathway
27259994	Endothelial SIRT1 prevents adverse arterial remodeling by facilitating HERC2-mediated degradation of acetylated LKB1
27259994	Methods and Results-Co-immunoprecipitation assay demonstrated that SIRT1, via its amino-terminus, binds to the DOC domain of HERC2 [HECT and RLD domain containing E3 ubiquitin protein ligase 2], which then ubiquitinates LKB1 in the nuclear compartment of endothelial cells
27259994	Site-directed mutagenesis revealed that acetylation at lysine (K) 64 of LKB1 triggers the formation of SIRT1/HERC2/LKB1 protein complex and subsequent proteasomal degradation
27259994	Chromatin immunoprecipitation quantitative PCR confirmed that acetylated LKB1 interacts with and activates TGFbeta1 promoter, which is inhibited by SIRT1
27259994	Knocking down either SIRT1 or HERC2 results in an increased association of LKB1 with the positive regulatory elements of TGFbeta1 promoter
27259994	In mice without endothelial nitric oxide synthase, selective overexpression of human SIRT1 in endothelium prevents hypertension and age-related adverse arterial remodeling
27259994	Lentiviral-mediated knockdown of HERC2 abolishes the beneficial effects of endothelial SIRT1 on both arterial remodeling and arterial blood pressure control
27259994	Conclusion-By downregulating acetylated LKB1 protein via HERC2, SIRT1 fine-tunes the crosstalk between endothelial and vascular smooth muscle cells to prevent adverse arterial remodeling and maintain vascular homeostasis
27582325	Resveratrol Protects against High-Fat Diet Induced Renal Pathological Damage and Cell Senescence by Activating SIRT1
27582325	Moreover, mice were fed with standard diet, standard diet plus resveratrol, high-fat diet or high-fat diet plus resveratrol for 3 months, and results show that resveratrol treatment prevents high-fat diet induced renal pathological damage by activating SIRT1, a key member in the mammalian sirtuin family that response to calorie restriction life-extension method
27508009	SRT1720, a SIRT1 specific activator, protected H2O2-induced senescent endothelium
27508009	Silent information regulator 1 (SIRT1) plays a critical role in maintaining vascular homeostasis via modulating senescent-related signal pathway, however, the molecular mechanism remains modest clarified
27508009	The purpose of this study was to examine whether SIRT1 specific activator SRT1720 would exhibit pro-angiogenic and anti-aging properties in response to hydrogen peroxide (H2O2)-induced endothelial senescence, and determine the underlying mechanisms
27508009	The results revealed that pharmacologic activation of SIRT1 by SRT1720 rescued apoptotic HUVECs and upregulated angiogenic response through reinforcing the protein expressions of angiogenic and survival factors in vitro
27237816	Carbocysteine counteracts the effects of cigarette smoke on cell growth and on the SIRT1/FoxO3 axis in bronchial epithelial cells
27237816	Altered proliferation and altered expression of anti-aging factors, including SIRT1 and FoxO3, characterise cellular senescence
27237816	The effects of carbocysteine on the SIRT1/FoxO3 axis and on downstream molecular mechanisms in human bronchial epithelial cells exposed to cigarette smoke are largely unknown
27237816	AIMS: Aim of this study was to explore whether carbocysteine modulated SIRT1/FoxO3 axis, and downstream molecular mechanisms associated to cellular senescence, in a bronchial epithelial cell line (16-HBE) exposed to cigarette smoke
27237816	Flow cytometry and clonogenic assay were used to assess cell proliferation; western blot analysis was used for assessing nuclear expression of SIRT1 and FoxO3
27237816	The nuclear co-localization of SIRT1 and FoxO3 was assessed by fluorescence microscopy
27237816	Beta galactosidase (a senescence marker) and SIRT1 activity were assessed by specific staining and colorimetric assays, respectively
27237816	RESULTS: CSE decreased cell proliferation, the nuclear expression of SIRT1 and FoxO3 and increased beta galactosidase staining
27237816	CSE, reduced SIRT1 activity and FoxO3 localization on survivin promoter thus increasing survivin expression
27237816	In CSE stimulated bronchial epithelial cells carbocysteine reverted these phenomena by increasing cell proliferation, and SIRT1 and FoxO3 nuclear expression, and by reducing beta galactosidase staining and survivin expression
27208501	Mechanistically, TIS21(/BTG2) regulated posttranslational modification of p53 via enhancing miR34a and Bax expressions as opposed to inhibiting SIRT1 and Bcl2 expression
27101740	Ergothioneine oxidation in the protection against high-glucose induced endothelial senescence: Involvement of SIRT1 and SIRT6
27101740	Notably, the Egt beneficial effect was exerted through the upregulation of sirtuin 1 (SIRT1) and sirtuin 6 (SIRT6) expression and the downregulation of p66Shc and NF-kappaB
27101740	These data provide the first evidence of the Egt ability to interfere with endothelial senescence linked to hyperglycaemia through the regulation of SIRT1 and SIRT6 signaling, thus further strengthening the already assessed role of these two histone deacetylases in type 2 diabetes
26971525	Sirt1: Role Under the Condition of Ischemia/Hypoxia
26971525	Silent information regulator factor 2-related enzyme 1 (sirtuin 1, Sirt1) is a nicotinamide adenine dinucleotide-dependent deacetylase, which can deacetylate histone and non-histone proteins and other transcription factors, and is involved in the regulation of many physiological functions, including cell senescence, gene transcription, energy balance, and oxidative stress
26971525	Studies have demonstrated that aging could enhance the vulnerability of brain, heart, lung, liver, and kidney to ischemia/hypoxia injury and the susceptibility in old folks to ischemia/hypoxia injury might be associated with Sirt1
26971525	In this review, we mainly summarize the role of Sirt1 in modulating pathways against energy depletion and its involvement in oxidative stress, apoptosis, and inflammation under the condition of ischemia/hypoxia
26948035	Seven SIRT family members have been identified in mammals, from SIRT1, the best studied for its role in vascular aging, to SIRT7
26948035	SIRT1 and SIRT2 are localized in the nucleus and cytoplasm
26948035	Previous mechanistic studies have revealed in detail that SIRT1, SIRT3, and SIRT6 show protective functions against vascular aging, and definite vascular function of other SIRTs is under investigation
26940203	SIRT1 alleviates senescence of degenerative human intervertebral disc cartilage endo-plate cells via the p53/p21 pathway
26940203	SIRT1 is a longevity gene that plays a pivotal role in many cellular functions, including cell senescence
26940203	Furthermore, SIRT1 was found to be capable of alleviating the oxidative stress-induced senescence of CEP cells in humans via p53/p21 pathway
26923269	Regulation of SIRT1 in aging: Roles in mitochondrial function and biogenesis
26923269	Silent information regulator-1, also known as sirtuin 1 (SIRT1), has been reported to be involved in the regulation of various important biological processes, including inflammation, mitochondrial biogenesis, as well as cell senescence and consequent aging
26923269	The level of SIRT1 is decreased in both transcriptional and postranscriptional conditions during aging, accompanied by attenuated mitochondrial biogenesis, an important component of aging-related diseases
26923269	Over the last decade, extensive studies have demonstrated that SIRT1 can activate several transcriptional factors, such as peroxisome proliferator activated receptor gamma co-activator 1alpha (PGC-1alpha) and hypoxia-inducible factor 1alpha (HIF-1alpha) resulting in ameliorated mitochondria biogenesis and extended life span
26923269	In this review, we focus on the molecular regulation of SIRT1 and its role in mitochondrial biogenesis during in the context of aging and aging-related diseases
26890602	In addition, the mechanistic relationship of autophagic flux and NAD(+) synthesis and the involvement of mTOR and Sirt1 activities were assessed
26814705	Furthermore, NP treatment induced the activation of Nrf2- and FOXO3A-mediated cellular stress responses, including an increased expression of heme oxygenease (HO-1), sirtuin (SIRT1), and DNA methyltransferase II (DNMT2)
26657715	SIRT1 in Endothelial Cells as a Novel Target for the Prevention of Early Vascular Aging
26657715	Sirtuin 1 (SIRT1), the mammalian ortholog of yeast longevity regulator Sir2, is a nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylase that elicits a variety of vasoprotective functions
26657715	Overexpression of SIRT1 in endothelium prevents cellular senescence, enhances vasodilatory responses, and attenuates ageing-induced vascular damages
26657715	The present review summarizes the recent progresses related to SIRT1-mediated beneficial effects on the prevention of early vascular ageing and discusses the potential of SIRT1 in endothelial cells as an antivascular ageing target
26637971	Recently, it has been reported that senescence-associated microRNA (miR)-195 targets Sirtuin 1 (SIRT1) to advance cellular senescence
26637971	Expression of SIRT1 and telomerase reverse transcriptase (TERT) was downregulated in old SkMs, and transduction of old SkMs with lentiviral miR-195 inhibitor significantly restored their expression
26629991	Metformin and Resveratrol Inhibited High Glucose-Induced Metabolic Memory of Endothelial Senescence through SIRT1/p300/p53/p21 Pathway
26629991	In this study, we investigated the involvement of SIRT1 axis as well as the protective effects of resveratrol (RSV) and metformin (MET), two potent SIRT1 activators, during the occurrence of "metabolic memory" of cellular senescence (senescent "memory")
26629991	It was shown that HN incubation triggered persistent downregulation of deacetylase SIRT1 and upregulation of acetyltransferase p300, leading to sustained hyperacetylation (at K382) and activation of p53, and subsequent p53/p21-mediated senescent "memory
26629991	Interestingly, we found that SIRT1 and p300 could regulate each other in response to HN stimulation, suggesting that a delicate balance between acetyltransferases and deacetylases may be particularly important for sustained acetylation and activation of non-histone proteins (such as p53), and eventually the occurrence of "metabolic memory
26522327	We show that SIRT1, the human homolog of the Saccharomyces cerevisiae protein silent information regulator 2, which is involved in cellular senescence and possibly the response to inflammation, forms a stable complex with HMGB1 in murine macrophage RAW264
26522327	SIRT1 directly interacted with HMGB1 via its N-terminal lysine residues (28-30), and thereby inhibited HMGB1 release to improve survival in an experimental model of sepsis
26522327	By contrast, inflammatory stimuli such as lipopolysaccharide (LPS) and tumor necrosis factor-alpha promoted HMGB1 release by provoking its dissociation from SIRT1 dependent on acetylation, thereby increasing the association between HMGB1 and chromosome region maintenance 1, leading to HMGB1 translocation
26522327	In vivo infection with wild-type SIRT1 and HMGB1(K282930R), a hypo-acetylation mutant, improved survival (85
26522327	7%) during endotoxemia more than infection with wild-type SIRT1 and HMGB1-expressing adenovirus, indicating that the acetylation-dependent interaction between HMGB1 and SIRT1 is critical for LPS-induced lethality
26522327	Taken together, we propose that SIRT1 forms an anti-inflammatory complex with HMGB1, allowing cells to bypass the response to inflammation
26505814	We found that senescence-inducing treatments such as DNA damage and RNA polymerase I inhibition stimulate the binding between the nucleolar protein NML (nucleomethylin) and SirT1
26469953	The mechanism involves not only the inhibition of autophagy early induced by these stimuli in the pathway to senescence, but also the increase in levels and nuclear localization of both the cell cycle suppressors p53/p21 and the longevity promoters FOXO1A, FOXO3A and SIRT1
26466127	We have found that in the diabetic retinas there was an up-regulation of senescence-associated markers SA-beta-Gal, p16INK4a and miR34a, which correlated with decreased expression of SIRT1, a target of miR34a
26456654	Resveratrol is a sirtuin 1 (SIRT1) activator and can function as an anti-inflammatory and antioxidant factor
26456654	In this study, we found that resveratrol had different effects on MSC cultures according to their cell passage and SIRT1 expression
26456654	In early passage MSCs expressing SIRT1, resveratrol decreased ERK and GSK-3beta phosphorylation, suppressing beta-catenin activity
26456654	In contrast, in late passage MSCs, which did not express SIRT1, resveratrol increased ERK and GSK-3beta phosphorylation, activating beta-catenin
26456654	Our findings suggest that resveratrol can be effectively applied to early passage MSC cultures, whereas parameters such as cell passage and SIRT1 expression must be taken into consideration before applying resveratrol to late passage MSCs
26439987	MicroRNA-212 negatively regulates starvation induced autophagy in prostate cancer cells by inhibiting SIRT1 and is a modulator of angiogenesis and cellular senescence
26439987	Elucidating the functional role of miR-212, we demonstrate that miR-212 negatively modulates starvation induced autophagy in PCa cells by targeting sirtuin 1 (SIRT1)
26414199	HDAC4 stabilizes SIRT1 via sumoylation SIRT1 to delay cellular senescence
26414199	This study shows that the expression patterns of HDAC4 and Sirtuin 1 (SIRT1; the mammalian homolog of Sir2) are positively correlated during cellular senescence
26414199	Furthermore, it is demonstrated that HDAC4 increases endogenous SIRT1 expression by enhancing its sumoylation modification levels, thereby stabilizing its protein levels
26413932	SIRT1 Overexpression Maintains Cell Phenotype and Function of Endothelial Cells Derived from Induced Pluripotent Stem Cells
26413932	Sirtuin1 (SIRT1) is an NAD(+)-dependent deacetylase involved in the regulation of cell senescence, redox state, and inflammatory status
26413932	We hypothesize that overexpression of the SIRT1 gene in iPSC-ECs will maintain EC phenotype, function, and proliferative capacity by overcoming early cell senescence
26413932	SIRT1 gene was packaged into a lentiviral vector (LV-SIRT1) and transduced into iPSC-ECs at passage 4
26413932	Beginning with passage 5, iPSC-ECs exhibited a fibroblast-like morphology, whereas iPSC-ECs overexpressing SIRT1 maintained EC cobblestone morphology
26413932	SIRT1 overexpressing iPSC-ECs also exhibited a higher percentage of canonical markers of endothelia (LV-SIRT1 61
26413932	SIRT1 overexpressing iPSC-ECs continued to proliferate through passage 9 with high purity of EC-like characteristics, while iPSC-ECs without SIRT1 overexpression became senescent after passage 5
26413932	Taken together, SIRT1 overexpression in iPSC-ECs maintains EC phenotype, improves EC function, and extends cell lifespan, overcoming critical hurdles associated with the use of iPSC-ECs in translational research
26408226	In PC12 cells, treatment with glutamate induced senescent phenotypes as judged by the cell appearance and senescence-associated ss-galactosidase (SA-ssgal) in parallel with decreased SIRT1 and increased p53 expression
26408226	However, treatment with memantine decreased glutamate-induced senescent PC12 cells and reversed the changes in SIRT1 and p53 expression
26392399	Despite of the shortened telomere, the mitochondrial failure could be overcome through metabolic regulation by caloric restriction (CR) and its mediator Sirtuin 1 (SIRT1)
26392399	Researches have shown that mitochondrial metabolic reprogramming by CR and SIRT1 alleviates functional decline of BMMSCs in aging
26390028	Moreover, silencing miR-195 in OMSCs by transfection of miR-195 inhibitor significantly restored antiaging factors expression including Tert and Sirt1 as well as phosphorylation of Akt and FOXO1
26361874	The deacetylase Sirtuin 1 (SIRT1) regulates the timing of the clock through acetylation of BMAL1 and PER2 and controls the clock-dependent functions, which can also be affected by environmental stressors
26346823	Sirtuin 1 (SIRT1) has been linked to vascular health by upregulating endothelial nitric oxide synthase (eNOS), suppressing oxidative stress, and attenuating telomere shortening
26346823	We hypothesized that T2D gives rise to shortened leukocyte and vascular telomeres alongside reduced vascular SIRT1 expression and increased oxidative stress
26346823	T2D rats had blunted arterial SIRT1 and eNOS protein expression levels which were associated with reduced antioxidant defense capacity
26346823	Our findings suggest that hyperglycemia and a deficit in vascular SIRT1 per se are not sufficient to prematurely shorten vascular telomeres
26330291	We found that FK866 induced cell senescence and diminished cellular NAD(+) levels and SIRT1 activity (detected by acetylation of p53), and these effects were dramatically antagonized by co-treatment with nicotinic acid, nicotinamide, or NAD(+)
26330291	In contrast, the protein expression of SIRT1, AMP-activated protein kinase, mammalian target of rapamycin, and nicotinamide phosphoribosyltransferase (Nampt) was not affected by FK866
26260033	The same pattern was found for deacetylase sirtuin (SIRT)-1 (-57 and -29%), confirming that jet-lagged young rats have an intermediate aging profile
26235577	Curcumin Attenuates Hydrogen Peroxide-Induced Premature Senescence via the Activation of SIRT1 in Human Umbilical Vein Endothelial Cells
26235577	Treatment of HUVECs with H2O2 also down-regulated the phosphorylation of endothelial nitric oxide synthase (eNOS), decreased the level of nitric oxide in the culture medium, and inhibited the protein expression and enzymatic activity of silent information regulator 1 (SIRT1), while pretreatment with curcumin partly reversed these effects (all p<0
26235577	Treatment with curcumin alone enhanced the enzymatic activity of SIRT1, but didn't affect cellular senescence, cell growth or apoptosis compared to the Control
26235577	The inhibition of SIRT1 using SIRT1 short interfering RNA (siRNA) could decrease the expression and phosphorylation of eNOS and abrogate the protective effect of curcumin on H2O2-induced premature senescence
26235577	These findings suggest that curcumin could attenuate oxidative stress-induced HUVECs' premature senescence via the activation of SIRT1
26219912	Aspirin increased the senescence of CRC cells, increased the protein levels of SIRT1, phospho-AMPK (T172), and phospho-acetyl CoA carboxylase (S79), and reduced the cellular level of ATP
26219912	In contrast, treatment with a SIRT1 agonist or an AMP analog induced cellular senescence
26219912	During the progression of aspirin-induced cellular senescence in CRC cells, SIRT1 showed increased deacetylase activity at a relatively early time point but was characterized by decreased activity with increased cytoplasmic localization at a later time point
26194321	Donepezil attenuates high glucose-accelerated senescence in human umbilical vein endothelial cells through SIRT1 activation
26194321	Pretreatment with nicotinamide (NAM), a sirtuin 1 (SIRT1) inhibitor, inhibited the reduction in senescence associated with donepezil
26194321	Indeed, our results indicated that donepezil increased the SIRT1 enzyme activity
26194321	Therefore, these results show that donepezil delays cellular senescence that is promoted under HG condition via activation of SIRT1
26171229	Pharmacological experiments suggested a reduced involvement of SKC a and Na-K ATPase and activation of adenosine monophosphate-activated protein kinase and silent information regulator T1 (sirtuin-1; SIRT1) in mesenteric arteries of 12-week-old SHR
26112889	This review focuses on the cardiovascular effects of Sirt1, Sirt3, Sirt6, and Sirt7
26112889	Most is known about Sirt1
26112889	Given the availability of specific Sirt1 activators or pan-sirtuin activators that boost levels of the sirtuin cofactor NAD(+), we anticipate that this field will move quickly from bench to bedside
26106036	HIS and telomere erosion in HMECs correlate with misregulation of SIRT1 leading to increased levels of acetylated pRb as well as acetylated H4K16 both globally and at telomeric regions
25975679	Inhibition of SIRT1 by sirtinol counteracted the protective effects of melatonin, suggesting that melatonin reversed the senescence in cells through the SIRT1-dependent pathway
25945449	RESULTS: Different transcriptional profiles were observed in young, pre-senescent and senescent HDFs, in which cellular aging increased AKT, FOXO3, CDKN1A and RSK1 mRNA expression level, but decreased ELK1, FOS and SIRT1 mRNA expression level
25945449	The three down-regulated mRNA in cellular aging, ELK1, FOS and SIRT1, were increased with tocotrienol-rich fraction treatment
25938935	Stress-mediated post-translational modification of molecular clock proteins, brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (BMAL1) and PERIOD 2, is associated with a reduction in the activity/level of the deacetylase sirtuin 1 (SIRT1)
25924011	Resveratrol Induced Premature Senescence Is Associated with DNA Damage Mediated SIRT1 and SIRT2 Down-Regulation
25924011	Resveratrol's anti-aging effects both in vitro and in vivo attributed to activation of a (NAD)-dependent histone deacetylase family member sirtuin-1 (SIRT1) protein
25924011	Among those, SIRT1 is the most extensively studied with perceptive effects on mammalian physiology and suppression of the diseases of aging
25924011	Current study was undertaken to investigate the effects of resveratrol in human primary dermal fibroblasts (BJ) and to clarify the role of sirtuin family members in particular SIRT1 and SIRT2 that are known to be involved in cellular stress responses and cell cycle, respectively
25924011	Interestingly, at concentrations where resveratrol induced premature senescence we show a significant decrease in SIRT1 and SIRT2 levels by Western Blot and quantitative RT-PCR analysis
25924011	Conversely inhibition of SIRT1 and SIRT2 via siRNA or sirtinol treatment also induced senescence in BJ fibroblasts associated with increased SA-beta-gal activity, gamma-H2AX phosphorylation and p53, p21CIP1 and p16INK4A levels
25924011	Interestingly DNA damaging agent doxorubicin also induced senescence in BJ fibroblasts associated with decreased SIRT1/2 levels
25924011	In conclusion our data reveal that resveratrol induced premature senescence is associated with SIRT1 and SIRT2 down regulation in human dermal fibroblasts
25924011	Here we suggest that the concomitant decline in SIRT1/2 expression in response to resveratrol treatment may be a cause for induction of senescence, which is most likely mediated by a regulatory mechanism activated by DNA damage response
25920189	In last ten years, lots of studies showed that SIRT1 exerts a protective effect in the progression of the diabetic nephropathy by promoting reconstruction of energy homeostasis, modulating cell redox state, resisting cell apoptosis, inhibiting inflammation and ameliorating renal fibrosis
25920189	SIRT1 has become a potential new target for the treatment of diabetic nephropathy
25914755	Endothelial Cell Senescence Increases Traction Forces due to Age-Associated Changes in the Glycocalyx and SIRT1
25914755	In this study, we sought to determine whether EC senescence increases traction forces through age-associated changes in the glycocalyx and antioxidant regulator deacetylase Sirtuin1 (SIRT1), which is downregulated during aging
25914755	While inhibition of SIRT1 had no significant effect on traction forces or actin organization for young cells, activation of SIRT1 did reduce traction forces and increase peripheral actin in aged ECs
25914755	These results show that EC senescence increases traction forces and alters actin localization through changes to SIRT1 and the glycocalyx
25907989	Amongst the seven known mammalian sirtuin proteins, SIRT1 has gained much attention due to its widely acknowledged roles in promoting longevity and ameliorating age-associated pathologies
25906418	The knockdown of CARM1 in LA4 cells led to decreased sirtuin 1 expression (0
25874702	To assess the cellular senescence of cultured-EPCs, the expression level of sirtuin-1 mRNA and the number of SA-beta-gal positive cell were evaluated
25874702	On the other hand, in microalbuminuria group at day-7, the level of sirtuin-1 mRNA expression of cultured-EPCs was significantly decreased (7
25855056	Here, we use an in vitro model of CR to study the effects of this dietary regime on replicative senescence, cellular lifespan and modulation of the SIRT1 signaling pathway in normal human diploid fibroblasts
25855056	These effects correlated with CR-mediated increases in SIRT1 and decreases in p53 expression levels
25855056	In addition, we show that manipulation of SIRT1 levels by either over-expression or siRNA-mediated knockdown resulted in delayed and accelerated cellular senescence, respectively
25855056	Our results demonstrate that CR can delay senescence and increase replicative lifespan of normal human diploid fibroblasts in vitro and suggest that SIRT1 plays an important role in these processes
25847123	SirT1 and STAT3 protect retinal pigmented epithelium cells against oxidative stress
25847123	It has been previously demonstrated that there are interactions between sirtuin 1 (SirT1) and signal transducer and activator of transcription 3 (STAT3), which have versatile roles in various microenvironments
25847123	The present study aimed to investigate the interactions between SirT1 and STAT3 in RPEs, following exposure to oxidative stress
25847123	The results revealed a downregulation of SirT1 expression, and an upregulation of STAT3 expression during oxidative stress
25847123	Further investigation indicated that SirT1 protected RPEs from oxidative stress-induced damage
25847123	Furthermore, gain- and loss-of-function experiments indicated that SirT1 had negative effects on the regulation of STAT3 expression in RPEs during oxidative stress
25847123	Notably, STAT3 directly protected the cells from oxidative stress, rather than depending on SirT1
25847123	In conclusion, SirT1 had negative effects on the regulation of STAT3 expression during oxidative stress
25847123	However, SirT1 and STAT3 demonstrated protective roles against oxidative stress in RPEs
25835220	METHODS: We measured the expression of the deacetylase Sirtuin 1 (Sirt1) and its transcriptional target Forkhead box O3a (Foxo3a); TBARS, a well-known marker of overall oxidative stress, and catalase activity as index of antioxidation
25835220	RESULTS: Under oxidative stress induction older cells showed a progressive decrease of Sirt1 and Foxo3a expression, persistently high TBARS levels with high, but ineffective Cat activity to counteract such levels
25835220	This dysfunction involves the pathway of Sirt1 a critical regulator of oxidative stress response and cellular lifespan, underlining its crucial role in endothelial homeostasis control during aging and age-associated diseases
25654692	We found that H2O2 treatment resulted in the expression of senescence characteristics in the ADSCs, including decreased proliferation rate, increased senescence-associated beta-galactosidase (SA-beta-gal) activity, decreased silent mating type information regulation 2 homolog (SIRT1) expression, and decreased telomerase activity
25654692	However, TC treatment was sufficient to rescue or reduce the effects of H2O2 induction, ultimately leading to an increased proliferation rate, a decrease in the percentage of SA-beta-gal-positive cells, upregulation of SIRT1 expression, and increased telomerase activity of the senescent ADSCs at the cellular level
25647160	In addition, we found that treatment of keratinocytes with Ex527, a specific inhibitor of sirtuin 1 (SIRT1), attenuated the ability of resveratrol to suppress senescence
25647160	In keeping with the latter observation, we noted that compared to non-senescent keratinocytes, senescent cells lacked SIRT1
25647160	Collectively, these findings suggest that the effects of resveratrol on keratinocyte senescence and proliferation are regulated by the AMPK-FOXO3 pathway and in some situations, but not all, by SIRT1
25635860	SIRT1 suppresses the senescence-associated secretory phenotype through epigenetic gene regulation
25635860	We herein demonstrated that the expression of Sirtuin1 (SIRT1) was decreased and the expression of SASP components was reciprocally increased during cellular senescence
25635860	The mRNAs and proteins of SASP components, such as IL-6 and IL-8, quickly accumulated in SIRT1-depleted cells, and the levels of these factors were also higher than those in control cells, indicating that SIRT1 negatively regulated the expression of SASP factors at the transcriptional level
25635860	SIRT1 bound to the promoter regions of IL-8 and IL-6, but dissociated from them during cellular senescence
25635860	These results suggest that SIRT1 repressed the expression of SASP factors through the deacetylation of histones in their promoter regions
25565110	HF-Cas-fed rats had increased caveolin-1 and down-regulated Sirt1 leading to activations of PPARgamma and p53/p21; whereas, rats fed HF-SPI suppressed caveolin-1and activated Sirt1 to de-acetylate PPARgamma and p53 in bone
25536029	Adaptation was neither prevented by antioxidants nor associated with increased PGC1-alpha/SIRT1/mTOR levels
25512378	Oxidative stress-induced inhibition of Sirt1 by caveolin-1 promotes p53-dependent premature senescence and stimulates the secretion of interleukin 6 (IL-6)
25512378	Sirtuin 1 (Sirt1) is a class III histone deacetylase that regulates a variety of physiological processes, including senescence
25512378	We found that caveolin-1, a structural protein component of caveolar membranes, is a direct binding partner of Sirt1, as shown by the binding of the scaffolding domain of caveolin-1 (amino acids 82-101) to the caveolin-binding domain of Sirt1 (amino acids 310-317)
25512378	Our data show that oxidative stress promotes the sequestration of Sirt1 into caveolar membranes and the interaction of Sirt1 with caveolin-1, which lead to inhibition of Sirt1 activity
25512378	Either down-regulation of Sirt1 expression or re-expression of caveolin-1 in caveolin-1 null MEFs restores reactive oxygen species-induced acetylation of p53 and premature senescence
25512378	Phosphorylation of caveolin-1 on tyrosine 14 promotes the sequestration of Sirt1 into caveolar membranes and activates p53/senescence signaling
25512378	We also identified IL-6 as a caveolin-1-specific cytokine that is secreted by senescent fibroblasts following the caveolin-1-mediated inhibition of Sirt1
25512378	Therefore, by inhibiting Sirt1, caveolin-1 links free radicals to the activation of the p53/senescence pathway and the protumorigenic properties of IL-6
25490147	HF-Cas-fed rats had increased caveolin-1 and down-regulated Sirt1, leading to activations of peroxisome proliferator-activated receptor gamma (PPARgamma) and p53/p21, whereas rats fed HF-SPI suppressed caveolin-1 and activated Sirt1 to deacetylate PPARgamma and p53 in bone
25415045	Sirtuin 1 Activator SRT1720 Protects Against Lung Injury via Reduction of Type II Alveolar Epithelial Cells Apoptosis in Emphysema
25415045	Sirtuin 1 (SIRT1), a NAD(+)-dependent histone deacetylase, regulates many pathophysiological processes including inflammation, apoptosis, cellular senescence and stress resistance
25415045	The main aim of this study was to investigate whether SRT1720, a pharmacological SIRT1 activator, could protect against AECII apoptosis in rats with emphysema caused by cigarette smoke exposure and intratracheal lipopolysaccharide instillation in vivo
25352462	MicroRNA-34a Induces Vascular Smooth Muscle Cells Senescence by SIRT1 Downregulation and Promotes the Expression of Age-Associated Pro-inflammatory Secretory Factors
25352462	Moreover, its well-known target, the longevity-associated protein SIRT1, was significantly downregulated during aging in both endothelial cells and vascular smooth muscle cells
25352462	Increased miR-34a as well as decreased SIRT1 expression was also observed in replicative-senescent human aortic smooth muscle cells
25352462	Finally, SIRT1 protein significantly decreased upon miR-34a overexpression and restoration of its levels rescued miR-34a-dependent human aortic smooth muscle cells senescence, but not senescence-associated secretory phenotype factors upregulation
25352462	Taken together, our findings suggest that aging-associated increase of miR-34a expression levels, by promoting vascular smooth muscle cells senescence and inflammation through SIRT1 downregulation and senescence-associated secretory phenotype factors induction, respectively, may lead to arterial dysfunctions
25304127	In the lungs, SIRT1 inhibits autophagy, cellular senescence, fibrosis, and inflammation by deacetylation of target proteins using NAD(+) as co-substrate and is therefore linked to the redox state
25286678	OBJECTIVE: To study the relationship between SIRT1 and glaucoma trabecular meshwork cell (GTM) cell on DNA double-strand breaks (DSBs) repair capability and resist cellular senescence
25286678	METHODS: The expressions of SIRT1 in GTM and normal trabecular meshwork (HTM) cell detected by RT-RCR and Western blot; HTM and GTM cells divided into four groups separately: Res group (treat cells with 0
25286678	The expression level of SIRT1 in groups was detected by Western blot
25286678	RESULTS: The expression of SIRT1 were observed in both HTM and GTM cells, but the expression level in HTM was higher than that of GTM cells have the ability to express SIRT1, however the expression of SIRT1 was lower than HTM
25286678	Expression levels of SIRT1 presented following treads: Res > Control > microRNA34a > SIRT1-ShRNA
25286678	CONCLUSION: SIRT1 may be useful in predicting the development and prognosis of glaucoma; Res promotes the expression of SIRT1 significantly, and the SIRT1 may protects GTM from oxidative stress-induced DSBs, aging even apoptosis, and promotes cell cycle arrest, which may provide a new target to treat glaucoma
25229978	Recent reports showed that peroxisome proliferator activated receptor gamma (PPARgamma) deacetylation by SIRT1 is involved in delaying cellular senescence and maintaining the brown remodeling of white adipose tissue
25229978	Acetylation of lysine 154 was identified by mass spectrometry (MS) while deacetylation of lysine 155 by SIRT1 was confirmed by in vitro deacetylation assay
25229978	The conserved acetylation sites of Ppargamma1 and the catalytic domain of SIRT1 are both required for the interaction between Ppargamma1 and SIRT1
25229978	Sirt1 and Ppargamma1 converge to govern lipid metabolism in vivo
25189993	Identification of a novel polyprenylated acylphloroglucinolderived SIRT1 inhibitor with cancerspecific anti-proliferative and invasion-suppressing activities
25189993	SIRT1, a class III histone deacetylase, plays a critical role in regulating cancer cell growth, migration and invasion, which makes it a potential target for cancer therapeutics
25189993	In this study, we screened derivatives of several groups of natural products and identified a novel SIRT1 inhibitor JQ-101, a synthetic derivative of the polyprenylated acylphloroglucinol (PPAP) natural products, with an IC(50) for SIRT1 of 30 microM in vitro, with 5-fold higher activity for SIRT1 vs
25189993	Exposure of tumor cells to JQ-101 significantly enhanced acetylation of p53 and histone H4K16 at known sites of SIRT1 deacetylation, validating SIRT1 as its cellular target
25189993	JQ-101 suppressed cancer cell growth and survival by targeting SIRT1, and also exhibited selective cytotoxicity towards a panel of human tumor cell lines, while producing no toxicity in two normal human cell types at comparable concentrations
25189993	In summary, we have identified JQ-101 as a new SIRT1 inhibitor which may have potential application in cancer treatment through its ability to induce tumor cell apoptosis and senescence and suppress cancer cell invasion
25186470	Knockdown of FOXO1 and FOXO1+3 resulted in significant reductions in levels of glutathione peroxidase 1 (GPX-1), catalase, light chain 3 (LC3), Beclin1, and sirtuin 1 (SIRT-1) proteins following treatment with tBHP
25184156	Sirt1 is the major sirtuin and has been shown to involve various cellular processes, including antiapoptosis, cellular senescence
25184156	Sirt1 was reported to be overexpressed in many cancers, including lung cancer
25184156	Sirtinol, a specific inhibitor of Sirt1, has been shown to induce apoptosis of cancer cells by elevating endogenous level of reactive oxygen species
25184156	On the contrary, sirtinol treatment causes the significantly increased level of FoxO3a, a proapoptotic transcription factor targeted by Sirt1
25184156	Overall, this study demonstrates that sirtinol attenuates the proliferation and induces apoptosis of NSCLC cells, indicating the potential treatment against NSCLC cells by inhibiting Sirt1 in future applications
25165029	Molecular Insights into SIRT1 Protection Against UVB-Induced Skin Fibroblast Senescence by Suppression of Oxidative Stress and p53 Acetylation
25165029	This study was designed to investigate the protective effect of Sirtuin1 (SIRT1) on the UVB-induced premature senescence
25165029	However, adenovirus-mediated SIRT1 overexpression significantly protected fibroblasts from UVB-induced cellular deterioration
25165029	Molecular analysis demonstrated that deacetylation of Forkhead box O3alpha (FOXO3alpha) by SIRT1 changed the transcriptional activity of FOXO3alpha and increased resistance to the oxidative stress
25165029	In addition, SIRT1 suppressed UVB-induced p53 acetylation and its transcriptional activity, which directly affected the cell cycle arrest induced by UVB
25165029	Further study demonstrated that SIRT1 activation inhibited cell senescence in the skin of the HR1 hairless mouse exposed to UVB
25165029	The study identifies a new role for SIRT1 in the UVB-induced senescence of skin fibroblats and provides a potential target for skin protection through molecuar insights into the mechanisms responsible for UVB-induced photoaging
25148910	Exercise training enhanced SIRT1 longevity signaling replaces the IGF1 survival pathway to attenuate aging-induced rat heart apoptosis
25148910	SIRT1 regulates important cellular processes, including anti-apoptosis, neuronal protection, cellular senescence, aging, and longevity
25148910	However, levels of SIRT1 and its downstream target PGC-1alpha were found to increase with age and compensatory performance
25132913	No significant change was observed on the expression of CCND1, SIRT1, and miR-34a upstream transcriptional regulator, TP53
25070626	We show that prolonged IGF-1 treatment inhibits SIRT1 deacetylase activity, resulting in increased p53 acetylation as well as p53 stabilization and activation, thus leading to premature cellular senescence
25070626	In addition, either expression of SIRT1 or inhibition of p53 prevented IGF-1-induced premature cellular senescence
25000517	In this study, we investigate the molecular mechanisms behind SIRT1-induced potentiation of hTERT transcription and show that FOXO3a functions downstream of SIRT1 and prevents the induction of cellular senescence by enhancing hTERT gene expression
25000517	Taken together, this pathway might constitute the molecular basis for the anti-senescence effects of SIRT1 and FOXO3a
24959282	Sirt1 is a tumor promoter in lung adenocarcinoma
24959282	Sirtuin 1 (Sirt1) is a nicotinamide adenine dinucleotide-dependent class III histone deacetylase
24959282	Notably, previous data have indicated that Sirt1 is both a tumor promoter and a tumor suppressor in tumorigenesis
24959282	However, Sirt1 expression in primary lung adenocarcinoma remains unknown
24959282	Immunohistochemical staining was performed to investigate Sirt1 expression in cancer cells in 125 consecutive resected cases of primary lung adenocarcinoma
24959282	Sirt1 expression was found to be increased in 26 (20
24959282	In the Sirt1-positive expression group, Sirt1 expression correlated with a higher Ki67 index and higher TNM classification, particularly for lymph node invasion and metastasis, and with a higher number of pulmonary vein invasion and lymphatic duct invasion
24959282	These results indicate that Sirt1 overexpression plays a promotional role in tumorigenesis and is closely associated with invasion and metastasis and, thus, it may be associated with prognosis
24917814	SIRT1 ameliorates age-related senescence of mesenchymal stem cells via modulating telomere shelterin
24917814	Here, we describe the effects of SIRT1, a NAD(+)-dependent deacetylase, on age-related MSCs senescence
24917814	Knockdown of SIRT1 in young MSCs induced cellular senescence and inhibited cell proliferation whereas overexpression of SIRT1 in aged MSCs reversed the senescence phenotype and stimulated cell proliferation
24917814	These results suggest that SIRT1 plays a key role in modulating age-induced MSCs senescence
24917814	SIRT1 protected MSCs from age-related DNA damage, induced telomerase reverse transcriptase (TERT) expression and enhanced telomerase activity but did not affect telomere length
24917814	SIRT1 positively regulated the expression of tripeptidyl peptidase 1 (TPP1), a component of the shelterin pathway that protects chromosome ends from DNA damage
24917814	Together, the results demonstrate that SIRT1 quenches age-related MSCs senescence by mechanisms that include enhanced TPP1 expression, increased telomerase activity and reduced DNA damage
24878874	However, adipose tissue-emanated SASP depress sirtuin-1 expression, leading adipocytes to a perpetual state of unresolved inflammation, due to a dampening of the heat shock response
24729935	Studies have identified alterations in the level or activity of factors such as SIRT1, PGC-1alpha, HIF-1alpha and c-MYC involved in key regulatory processes in the maintenance of mitochondrial structural integrity, biogenesis and function
24729176	Hydrogen sulfide delays nicotinamide-induced premature senescence via upregulation of SIRT1 in human umbilical vein endothelial cells
24729176	The premature senescence-like phenotype HUVECs (the fourth passage) was induced by treatment with nicotinamide (NAM, an inhibitor of SIRT1, 5 mmol/L, 12 h)
24729176	The mRNA and protein levels of SIRT1 were detected using RT-PCR and western blotting analysis, respectively
24729176	Furthermore, we found that both on protein and mRNA levels of SIRT1 in the Y+N+S50 group was significantly increased compared with that in Y+N group
24729176	In conclusion, NaHS delays senescence of HUVECs induced by NAM via upregulation of SIRT1 expression
24727683	In the current study, we sought to examine whether IS regulates sirtuin 1 (Sirt1) and affects endothelial senescence via AhR activation
24727683	The intracellular nicotinamide phosphoribosyltransferase (iNampt) activity, cellular NAD()/NADPH ratio and Sirt1 activity were analyzed according to a colorimetric assay to determine the mechanism of cellular senescence
24727683	RESULTS: IS decreased the iNampt activity, NAD()/NADPH ratio and Sirt1 activity, resulting in an increase in the percentage of SA beta-gal-positive cells
24697269	In an effort to identify small molecule inhibitors of sirtuins for potential use as chemotherapeutics as well as tools to modulate sirtuin activity, we previously identified a nonselective sirtuin inhibitor called cambinol (IC50 approximately 50 muM for SIRT1 and SIRT2) with in vitro and in vivo antilymphoma activity
24697269	8-fold selectivity for SIRT1, 24 with >15
24697269	3-fold selectivity for SIRT3 versus SIRT1 and SIRT2, respectively
24697269	In vitro cytotoxicity studies with these compounds as well as EX527, a potent and selective SIRT1 inhibitor, suggest that antilymphoma activity of this compound class may be predominantly due to SIRT2 inhibition
24651677	However, pharmacological activation of sirtuin 1 (using resveratrol or SRT1720) protected ECs from disturbed flow-induced senescence
24651677	CONCLUSIONS: Disturbed flow promotes endothelial senescence via a p53-p21-dependent pathway which can be inhibited by activation of sirtuin 1
24651677	These observations support the principle that pharmacological activation of sirtuin 1 may promote cardiovascular health by suppressing EC senescence at atheroprone sites
24473773	1 binds with high affinity O-acetyl ADP ribose, a small metabolite produced by the reaction catalysed by NAD+-dependent deacetylase SIRT1, whereas macroH2A1
24405415	The HUVECs treated with KP exhibited the senescent phenotype, as determined using a senescence-associated beta-galactosidase assay, cell morphology analysis, and decreased Sirt1 (sirtuin 1) expression and increased p53 expression shown by Western blot analysis
24367027	SIRT1, a representative sirtuin family, has been demonstrated to activate autophagy, but a role for SIRT6 in autophagy activation has not been shown
24238886	This study revealed that mussel oligopeptides could protect against cellular senescence induced by H2O2, and the effects were closely associated with redox cycle modulating and potentiating the SIRT1 pathway
24078830	Bisdemethoxycurcumin Increases Sirt1 to Antagonize t-BHP-Induced Premature Senescence in WI38 Fibroblast Cells
24078830	Notably, we found that BDMC treatment activated Sirt1/AMPK signaling pathway
24078830	Moreover, downregulating Sirt1 by the pharmacological inhibitor nicotianamine or small interfering RNA blocked BDMC-mediated protection against t-BHP-mediated decrease in proliferation
24078830	These results suggested that BDMC prevented t-BHP-induced cellular senescence, and BDMC-induced Sirt1 may be a mechanism mediating its beneficial effects
23997094	Similarly, sirtuin expression was relatively well-preserved in aorta from both genotypes, whereas expression of SIRT1, SIRT2, SIRT3, SIRT4, and SIRT6 were significantly reduced in the aortic valve
23982736	Intriguingly, co-expression of SIRT1 and p53 dramatically reduced the levels of Ac-p53, however, low doses of metformin treatment partially reversed the effect of SIRT1 on p53 acetylation and elevated SA-beta-gal activity
23968571	The longevity regulator SIRT1 is an enzyme catalyzing the deacetylation of protein substrates, in turn modulating their biological functions
23968571	In aged arteries, SIRT1 expression and activity is blunted, which contributes to the development of atherosclerosis and abnormal vascular responses
23968571	A recent study suggests that cyclin-dependent kinase 5 (CDK5) is responsible for the phosphorylation of SIRT1 at the serine 47 residue
23968571	This modification blocks the anti-senescence activity of SIRT1 and plays a critical role in the loss-of-SIRT1 function during vascular ageing
23968571	Thus, by inhibiting CDK5, SIRT1 function can be improved, in turn preventing the development of atherosclerosis and slowing down the process of vascular ageing
23953979	Possible mechanisms that mediate the consequences of genomic instability at the local vascular and at the systemic level, such as cell senescence, mutations, mitochondrial damage, and sirtuin 1 and IGF-1 decrease, are discussed and important goals for future research are set
23897750	Senescence negatively correlated with the expression and activity of sirtuin-1 (SIRT1), a protein deacetylase that protects against DNA damage and cellular senescence
23897750	Inhibition of DNA damage response by silencing of ataxia telangiectasia mutated (ATM) kinase resulted in upregulation of SIRT1 expression and decreased senescence
23879090	NPCs at passage 7 were randomly divided into 3-D alginate microsphere control group (group A), RES group (group B), silent mating type information regulation 2 homolog 1 (SIRT1)- small interfering RNA (siRNA) + RES group (group C), and negative control-siRNA + RES group (group D); and NPCs in the in-vitro monolayer culture was monolayer control group (group E)
23879090	After corresponding treatment, Western blot was used for determining the protein expressions of SIRT1, Aggrecan, and collagen type II; real-time fluorescence quantitative PCR was used for detecting SIRT1 mRNA expression
23879090	The protein expressions of SIRT1, collagen type II, and Aggrecan in group B were significantly improved when compared with that in group A (P < 0
23879090	Real-time fluorescence quantitative PCR and Western blot showed that the expressions of SIRT1 mRNA and proteins in group C were significantly inhibited after transfected with SIRT1-siRNA when compared with those in groups B and D (P < 0
23879090	In 3-D alginate microsphere culture, RES could restore the phenotype of dedifferentiated NPCs and synthesize more extracellular matrix, which is related to the regulation of SIRT1
23744621	Stachydrine ameliorates high-glucose induced endothelial cell senescence and SIRT1 downregulation
23744621	Western blot analysis and confocal-laser scanning microscopy revealed that stachydrine also blocked the high-glucose induced upregulation of p16(INK4A) and downregulation of SIRT1 expression and enzyme activity
23744621	Taken together, results here presented are the first evidence that stachydrine, a naturally occurring compound abundant in citrus fruit juices, inhibits the deleterious effect of high-glucose on EC and acts through the modulation of SIRT1 pathway
23727633	Glucocorticoids induce senescence in primary human tenocytes by inhibition of sirtuin 1 and activation of the p53/p21 pathway: in vivo and in vitro evidence
23727633	Levels of the p53 deacetylase sirtuin 1 were lower in dexamethasone-treated cells compared with controls
23727633	Activation of sirtuin 1 either by exogenous overexpression or by treatment with resveratrol or low glucose prevented dexamethasone-induced senescence
23698802	SIRT1, heme oxygenase-1 and NO-mediated vasodilation in a human model of endogenous angiotensin II type 1 receptor antagonism: implications for hypertension
23698802	SIRT1 upregulates eNOS activity and inhibits endothelial cell senescence, and reduced SIRT1 is related to oxidative stress and reduced NO-dependent dilation
23698802	To our knowledge, in BS/GS patients SIRT1 has never been evaluated
23600198	OBJECTIVE: To determine miRNA-34a regulated cell senescence indirectly through targeting silent mating-type information regulation 2 homologue 1 (SIRT1) in vitro experiment
23600198	The expression levels of SIRT1 in each cell groups were detected by RT-PCR and Western blot
23600198	The HUVEC cells were divided into different group: transfected with pre-miRNA-34a expression vector (HUVEC-pre-miRNA-34a), transfected with miRNA-1792 expression vector (HUVEC-pre-miRNA-1792), treated HUVEC cell with SIRT1 activator resveratrol (final concentration 1 micromol/L, treatment for 2 h)(HUVEC-Res), and HUVEC cells without any treatment as the control
23600198	RT-PCR and Western blot indicated that the overexpression of miRNA-34a down regulated mRNA and protein level of SIRT1 in HEK293-miRNA-34a and HUVEC-miRNA-34a cell groups (P < 0
23600198	CONCLUSION: miRNA-34a regulated cell senescence indirectly through targeting SIRT1
23588928	Hydrogen sulfide prevents H(2)O(2)-induced senescence in human umbilical vein endothelial cells through SIRT1 activation
23588928	Pretreatment with nicotinamide (NAM), a sirtuin 1 (SIRT1) inhibitor, inhibited the reduction in senescence associated with H2S
23588928	Immunoblot analyses revealed that SIRT1 levels in senescent HUVECs treated with NaHS (60 microM) were indistinguishable from controls; however, analyses of SIRT1 activity indicated that SIRT1 enzyme activity was enhanced
23588928	The present study demonstrated that H2S protects against HUVEC senescence, potentially through modulation of SIRT1 activity
23549616	Upregulation of SIRT1 by 17beta-estradiol depends on ubiquitin-proteasome degradation of PPAR-gamma mediated by NEDD4-1
23549616	17beta-estradiol (E2) treatment of cells results in an upregulation of SIRT1 and a down-regulation of PPARgamma
23549616	Taken together, our data show that E2 could upregulate SIRT1 expression via promoting the PPARGamma ubiquitination-proteasome degradation pathway to delay the process of cell senescence
23542362	Redox regulation of SIRT1 in inflammation and cellular senescence
23542362	Sirtuin 1 (SIRT1) regulates inflammation, aging (life span and health span), calorie restriction/energetics, mitochondrial biogenesis, stress resistance, cellular senescence, endothelial functions, apoptosis/autophagy, and circadian rhythms through deacetylation of transcription factors and histones
23542362	SIRT1 level and activity are decreased in chronic inflammatory conditions and aging, in which oxidative stress occurs
23542362	SIRT1 is regulated by a NAD(+)-dependent DNA repair enzyme, poly(ADP-ribose) polymerase-1 (PARP1), and subsequent NAD(+) depletion by oxidative stress may have consequent effects on inflammatory and stress responses as well as cellular senescence
23542362	SIRT1 has been shown to undergo covalent oxidative modifications by cigarette smoke-derived oxidants/aldehydes, leading to posttranslational modifications, inactivation, and protein degradation
23542362	Furthermore, oxidant/carbonyl stress-mediated reduction of SIRT1 leads to the loss of its control on acetylation of target proteins including p53, RelA/p65, and FOXO3, thereby enhancing the inflammatory, prosenescent, and apoptotic responses, as well as endothelial dysfunction
23542362	In this review, the mechanisms of cigarette smoke/oxidant-mediated redox posttranslational modifications of SIRT1 and its roles in PARP1 and NF-kappaB activation, and FOXO3 and eNOS regulation, as well as chromatin remodeling/histone modifications during inflammaging, are discussed
23542362	Furthermore, we have also discussed various novel ways to activate SIRT1 either directly or indirectly, which may have therapeutic potential in attenuating inflammation and premature senescence involved in chronic lung diseases
23531985	Sirtuin 1 (SIRT1) deacetylase and p66 share overlapping biological functions but induce divergent phenotypes, including opposite effects on longevity, ROS metabolism, cell senescence, and apoptosis
23531985	Exciting new data from our laboratory show that SIRT1 is upregulated in the kidneys of p66 null Akita mice and decreases acetylation of p53, which destabilizes the p53 protein and prevents the transcription of p53 proapoptosis genes
23531985	Conversely, SIRT1 activates the transcription of FOXO3a-dependent stress gene programs that detoxify ROS and promote the survival phenotype
23525956	Identification of a small molecule activator of SIRT1 gene expression
23525956	Increased SIRT1 expression exerts beneficial effects in transgenic animal models, ameliorating the onset and progression of aging-related disease phenotypes in various organs including the heart
23525956	The potential beneficial effects of SIRT1 have made SIRT1 a prime therapeutic target for age-related diseases and considerable efforts led to the identification of small molecule activator of SIRT1 protein
23525956	Thus far, however, a small molecule activator of SIRT1 gene expression has not been reported
23525956	Here, we report that syringaresinol, isolated from Panax ginseng berry pulp, is an activator of SIRT1 gene expression
23525956	Using human umbilical endothelial cells (HUVECs), we show that syringaresinol treatment induced binding of FOXO3 to the SIRT1 promoter in a sequence-specific manner, leading to induction of SIRT1 expression
23525956	Increased SIRT1 expression in HUVECs by syringaresinol treatment delayed cellular senescence and improved various markers of endothelial functions in a FOXO3 dependent manner
23525956	Collectively, these findings bring to light a new transcription activator of SIRT1 that may have therapeutic potential
23430617	PGC-1alpha disruption results in reduced expression of the longevity-related deacetylase sirtuin 1 (SIRT1) and the antioxidant catalase, and increased expression of the senescence marker p53 in aortas
23430617	Further, angiotensin II, a major hormonal inducer of vascular senescence, induces prolonged lysine acetylation of PGC-1alpha and releases the PGC-1alpha-FoxO1 complex from the SIRT1 promoter, thus reducing SIRT1 expression
23430617	The phosphorylation-defective mutant PGC-1alpha S570A is not acetylated, is constitutively active for forkhead box O1-dependent SIRT1 transcription, and prevents angiotensin II-induced senescence
23430617	Acetylation of PGC-1alpha by angiotensin II interrupts the PGC-1alpha-forkhead box O1-SIRT1 feed-forward signaling circuit leading to SIRT1 and catalase downregulation and vascular senescence
23342163	We also found that p300 and SIRT1 regulate each other in such process, as silencing one led to increase of the others' expression
23342163	Chemically induced increased SIRT1 activity and p300 knockdown corrected these abnormalities slowing aging-like changes
23342163	Diabetic animals showed increased cellular senescence in renal glomerulus and retinal blood vessels along with reduced SIRT1 mRNA expressions in these tissues
23342163	Data from this study demonstrated that hyperglycemia accelerates aging-like process in the vascular ECs and such process is mediated via downregulation of SIRT1, causing reduction of mitochondrial antioxidant enzyme in a p300 and FOXO1 mediated pathway
23339189	SIRT1 is purposed to promote longevity and to suppress the initiation of some cancers
23339189	Nevertheless, SIRT1 is reported to function as a tumor suppressor as well as an oncogenic protein
23339189	In addition, human HCC cell lines (Hep3B, HepG2, HuH7, HLE, HLF, HepKK1, skHep1) were screened for the expression of the sirtuin family members and only SIRT1 was consistently overexpressed compared with normal hepatocytes
23339189	Knockdown or inhibition of SIRT1 activity had a cytostatic effect, characterized by an altered morphology, impaired proliferation, an increased expression of differentiation markers, and cellular senescence
23339189	In an orthotopic xenograft model, knockdown of SIRT1 resulted in 50% fewer animals developing tumors and cambinol treatment resulted in an overall lower tumor burden
23339189	Taken together, our data show that inhibition of SIRT1 in HCC cells impairs their proliferation in vitro and tumor formation in vivo
23332867	Sirtuin 1 (SIRT1): a potential immunohistochemical marker and therapeutic target in soft tissue neoplasms with myoid differentiation
23332867	Sirtuin, silent mating-type information regulation 2 homolog Saccharomyces cerevisiae 1 (SIRT1), is a protein that has been implicated in multiple mammalian functions including cell aging, stress resistance, and differentiation
23332867	SIRT1 has also been shown to be involved in multiple tumors
23332867	In addition, new pharmacotherapies have recently been approved that target SIRT1
23332867	The purpose of this study was to use immunohistochemistry to characterize SIRT1 protein expression in human soft tissue neoplasms with the hopes of finding new diagnostic and therapeutic modalities
23332867	SIRT1 immunoreactivity was reviewed in a series of 164 soft tissue tumors including alveolar soft part sarcoma, angiomyolipoma, clear cell sarcoma, desmoid/fibromatosis, desmoplastic small round cell tumor, Ewing sarcoma, gastrointestinal stromal tumor, glomus tumor, leiomyoma, leiomyosarcoma, lipoma, liposarcoma, malignant peripheral nerve sheath tumor, nodular fasciitis, osteosarcoma, rhabdomyosarcoma, schwannoma, solitary fibrous tumor, synovial sarcoma, undifferentiated pleomorphic sarcoma, and Wilms tumor
23332867	In addition, numerous benign tissues were tested for SIRT1 reactivity
23332867	In nonneoplastic tissue, strong cytoplasmic SIRT1 reactivity was observed in all prostate stroma, smooth muscle, and striated muscle
23332867	A similar pattern of cytoplasmic SIRT1 expression was observed in soft tissue neoplasms with myoid differentiation, namely, angiomyolipoma (100%), glomus tumor (100%), leiomyoma (90%), leiomyosarcoma (76
23332867	Although the physiologic role of SIRT1 remains to be clarified in myoid tissues and neoplasms differentiating along these lines, this observation points to a potential role for this marker in diagnostic immunohistochemistry
23332867	Furthermore, the recent emergence of drugs capable of selectively inhibiting SIRT1 raises the possibility of a potential application for targeted therapy
23332867	Additional studies are necessary to further characterise the role of SIRT1 in myoid tissues and neoplasms
23293221	Increasing evidence shows that resveratrol, enriched in certain foods, for example red grapes and wine, has anti-tumor and anti-aging effects on somatic tissues by influencing various signaling pathways, including anti-oxidation, as well as activating Sirt1 and telomerase
23259030	The involvement of Sirt1 and acetylated p53 was examined as an underlying mechanism for the senescence preventive activity of EGCG in HDFs
23259030	Furthermore, EGCG was found to prevent serial passage- and H(2)O(2)-induced senescence in HDFs by suppressing p53 acetylation, but the Sirt1 activity was unaffected
23224247	Vascular smooth muscle cell sirtuin 1 protects against DNA damage and inhibits atherosclerosis
23224247	Sirtuin 1 deacetylase (SIRT1) regulates cell ageing and energy metabolism and regulates the DNA damage response through multiple targets
23224247	However, the direct role of SIRT1 in atherosclerosis and how SIRT1 in VSMCs might regulate atherosclerosis are unknown
23224247	METHODS AND RESULTS: SIRT1 expression was reduced in human atherosclerotic plaques and VSMCs both derived from plaques and undergoing replicative senescence
23224247	SIRT1 inhibition reduced DNA repair and induced apoptosis, in part, through reduced activation of the repair protein Nijmegen Breakage Syndrome-1 but not p53
23224247	Fat feeding reduced SIRT1 and induced DNA damage in VSMCs
23224247	VSMCs from mice expressing inactive truncated SIRT1 (Deltaex4) showed increased oxidized low-density lipoprotein-induced DNA damage and senescence
23224247	CONCLUSIONS: SIRT1 is reduced in human atherosclerosis and is a critical regulator of the DNA damage response and survival in VSMCs
23224247	VSMC SIRT1 protects against DNA damage, medial degeneration, and atherosclerosis
23201774	METHODS AND RESULTS: mRNA expression analysis demonstrated comparable levels of SIRT1 and SIRT6 transcripts in endothelial cells derived from different vascular beds and significantly higher levels of SIRT6 in these cells relative to those in haematopoietic progenitor cells
23193674	Silent information regulator factor 2-related enzyme 1 (Sirtuins 1, SIRT1) is a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, which can deacetylate histone and non-histone proteins and other transcription factors, and is involved in the regulation of many physiological functions, including gene transcription, energy metabolism, cell senescence and oxidative stress
23193674	Recent studies show that through adjusting the activity of endothelial nitric oxide syntheses (eNOS), p53, forkhead box class O (FOXO) and nuclear factor kappa B (NF-kappaB), SIRT1 can protect the functions of vascular endothelia and nerves in a variety of pathological conditions
23193674	Therefore, SIRT1 may be used as a potential therapeutic target of these diseases, particularly erectile dysfunction, which are associated with endothelial dysfunction
23000914	The present study demonstrates that upregulation of SIRT1 by peroxisome proliferator-activated receptor (PPAR) delta attenuates premature senescence in angiotensin (Ang) II-treated human coronary artery endothelial cells (HCAECs)
23000914	A marked concentration- and time-dependent increase in the mRNA levels of SIRT1 was observed in GW501516-treated HCAECs
23000914	In addition, activation of PPARdelta, but not PPARalpha or PPARgamma, significantly enhanced SIRT1 promoter activity and protein expression
23000914	Down-regulation or inhibition of SIRT1 by siRNA or sirtinol abrogated the effects of PPARdelta on Ang II-induced premature senescence and ROS generation, respectively
23000914	Furthermore, resveratrol, a well-known activator of SIRT1, mimicked the action of PPARdelta on Ang II-induced premature senescence and ROS generation
23000914	Taken together, these results indicate that the anti-senescent activities of PPARdelta may be achieved at least in part by fine tuning the expression of SIRT1 in the vascular endothelium
22981429	THSG weekly activated SIRT1 activity, stimulated eNOS promoter reporter gene activity, and ameliorated H(2)O(2)-induced cellular senescence and K373 acetylation of p53 in cultured human umbilical vein endothelial cells (HUVECs)
22981429	CONCLUSIONS: THSG improves blood flow and ameliorates vascular senescence by increasing eNOS expression and Sirt1 activity and decreasing acetylation of p53 at K373 site, at least in part, both in vitro and in vivo
22971926	We also found that sirtuin 1 (SIRT1) deacetylase, a controller of cellular senescence, was decreased in MDH1 knockdown cells
22971926	These results indicate that the decrease in MDH1 and subsequent reduction in NAD/NADH ratio, which causes SIRT1 inhibition, is a likely carbohydrate metabolism-controlled cellular senescence mechanism
22964779	The aim of this study was to investigate the antiaging effects of simvastatin as well as its effects on sirtuin 1 (SIRT1) expression in endothelial cells
22964779	Aortic beta-galactosidase staining was undertaken to determine senescence, and SIRT1 protein expression was evaluated using Western blot analysis
22964779	After simvastatin therapy, arterial endothelial cell aging was significantly reduced, and SIRT1 expression was significantly increased
22964779	The OX-LDL significantly accelerated the senescence of umbilical vein endothelial cells and decreased SIRT1 expression
22964779	The OX-LDL-induced downregulation of SIRT1 was blocked by simvastatin
22964779	Simvastatin treatment also reduced umbilical vein endothelial cell aging and increased SIRT1 expression
22796566	Perspectives on translational and therapeutic aspects of SIRT1 in inflammaging and senescence
22796566	Sirtuin1 (SIRT1), a type III protein deacetylase, is considered as a novel anti-aging protein involved in regulation of cellular senescence/aging and inflammation
22796566	SIRT1 level and activity are decreased during lung inflammaging caused by oxidative stress
22796566	A variety of dietary polyphenols and pharmacological activators are shown to regulate SIRT1 so as to intervene the progression of type 2 diabetes, cancer, cardiovascular diseases, and chronic obstructive pulmonary disease associated with inflammaging
22796566	However, recent studies have shown the non-specific regulation of SIRT1 by the aforementioned pharmacological activators and polyphenols
22796566	In this perspective, we have briefly discussed the role of SIRT1 in regulation of cellular senescence and its associated secretory phenotype, DNA damage response, particularly in lung inflammaging and during the development of chronic obstructive pulmonary diseases
22796566	We have also discussed the potential directions for future translational therapeutic avenues for SIRT1 in modulating lung inflammaging associated with senescence in chronic lung diseases associated with increased oxidative stress
22788682	A majority of PAEC underwent accelerated senescence, as indicated by morphological changes, increased 21 kD cyclin-dependent kinase inhibitor (p21/waf1), decreased sirtuin 1 (SIRT1), and elevated senescence-associated beta-galactosidase (SA-beta-gal)
22783411	Effects of gambogic acid on the activation of caspase-3 and downregulation of SIRT1 in RPMI-8226 multiple myeloma cells via the accumulation of ROS
22783411	Mammalian SIRT1, as the closest homolog of the yeast Sir2, was extensively involved in regulating cell processes, including cell senescence, aging and neuronal protection, as well as having anti-apoptotic properties
22783411	Moreover, SIRT1 overexpression has been shown to protect cancer cells from chemotherapy and ionizing radiation
22783411	In the present study, we demonstrated that GA has the potential to downregulate the expression of SIRT1 via ROS accumulation
22753194	Cyclin-dependent kinase 5-mediated hyperphosphorylation of sirtuin-1 contributes to the development of endothelial senescence and atherosclerosis
22753194	Sirtuin-1 (SIRT1) is an NAD-dependent deacetylase possessing antiaging activities
22753194	During the occurrence of endothelial senescence, both the expression and activity of SIRT1 are downregulated
22753194	Western blotting revealed that phosphorylation of SIRT1 at serine 47 (S47) was significantly enhanced in senescent endothelial cells
22753194	Mutation of S47 to nonphosphorable alanine (S47A) enhanced whereas replacing S47 with phospho-mimicking aspartic acid (S47D) abolished the antisenescent, growth-promoting, and LKB1-downregulating actions of SIRT1
22753194	Phosphorylation at S47 was critically involved in the nuclear retention of SIRT1 but abolished its association with the telomeric repeat-binding factor 2-interacting protein 1
22753194	Cyclin-dependent kinase 5 (CDK5) was identified as an SIRT1 kinase modulating S47 phosphorylation
22753194	Knockdown or inhibition of CDK5 reduced the number of senescent endothelial cells, promoted nuclear exportation of SIRT1, and attenuated the expression of inflammatory genes in porcine aortic endothelial cells
22753194	CONCLUSION: CDK5-mediated hyperphosphorylation of SIRT1 facilitates the development of endothelial senescence and atherosclerosis
22744176	Endothelium-specific SIRT1 overexpression inhibits hyperglycemia-induced upregulation of vascular cell senescence
22744176	Mammalian sirtuin 1 (SIRT1) has been shown to decrease high-glucose-induced endothelial cell senescence in vitro and prevent hyperglycemia-induced vascular dysfunction
22744176	We used endothelium-specific SIRT1 transgenic (SIRT1-Tg) mice and wild-type (WT) mice to construct a 40-week streptozotocin (STZ)-induced diabetic mouse model
22563892	NO and COX-2, in addition to activation of SIRT1, play a critical role in the inhibition of senescence induction in human endothelial cells by RWE
22555620	In this report, we show that OVX-induced bone loss is associated with profound decreases in collagen 1 and Sirt1
22555620	Finally, we demonstrated that bone cell senescence is associated with decreased Sirt1 expression and activated p53, p16, and p21
22552606	Hypermethylation of HIC1 promoter and aberrant expression of HIC1/SIRT1 might contribute to the carcinogenesis of pancreatic cancer
22552606	METHODS: Methylation of HIC1 promoter HIC1 and SIRT1 expression were detected in human normal pancreas (NP), CP and pancreatic adenocarcinoma tissues
22552606	CONCLUSIONS: Our results indicate that hypermethylation of HIC1 promoter in CP may contribute to the aberrant expression of HIC1/SIRT1 pathway and then involve in the pancreatic carcinogenesis
22546858	SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice
22546858	However, the molecular signals underlying the premature aging in lungs, and whether SIRT1 protects against cellular senescence and various pathophysiological alterations in emphysema, remain unknown
22546858	SIRT1 activation by both genetic overexpression and a selective pharmacological activator, SRT1720, attenuated stress-induced premature cellular senescence and protected against emphysema induced by cigarette smoke and elastase in mice
22546858	Ablation of Sirt1 in airway epithelium, but not in myeloid cells, aggravated airspace enlargement, impaired lung function, and reduced exercise tolerance
22546858	These effects were due to the ability of SIRT1 to deacetylate the FOXO3 transcription factor, since Foxo3 deficiency diminished the protective effect of SRT1720 on cellular senescence and emphysematous changes
22546858	Thus, SIRT1 protects against emphysema through FOXO3-mediated reduction of cellular senescence, independently of inflammation
22510478	This inhibition in large part resulted from the downregulation of SIRT1, which in turn was because of decrease in the expression of the translation regulator HuR
22284404	Resveratrol reduces vascular cell senescence through attenuation of oxidative stress by SIRT1/NADPH oxidase-dependent mechanisms
22284404	This study was undertaken to investigate the effects of resveratrol (Res) on amelioration of vascular cell aging and the role of SIRT1/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase pathway
22284404	Res protected against HFS- or high-glucose-induced increase in NADPH oxidase p47phox expression and decrease in SIRT1 level
22284404	Apocynin, a NADPH oxidase inhibitor, down-regulated p47phox protein expression, but had no influence on SIRT1 protein; sirtinol, a SIRT1 inhibitor, aggravated the decrease in SIRT1 protein level and the increase in p47phox protein expression induced by high glucose
22284404	The underlying mechanism is at least SIRT1/NADPH oxidase pathway dependent
22234173	Cathepsin cleavage of sirtuin 1 in endothelial progenitor cells mediates stress-induced premature senescence
22234173	In this study, we examined the impact of a range of cardiovascular risk factors on the expression of sirtuin 1 (SIRT1), SIPS, and apoptosis, and we documented the role of SIRT1 in reduced EC and endothelial progenitor cell (EPC) viability
22234173	These findings were confirmed in mice with selective endothelial SIRT1 knockout
22234173	We provide evidence that SIRT1 is an important substrate of cysteine cathepsins B, S, and L
22234173	An antioxidant/peroxynitrite scavenger, ebselen, prevented stress-induced SIRT1 depletion and subversion of autophagy by mitigating lysosomal dysfunction
22234173	In conclusion, our data advance the concept of "stem cell aging" by establishing the critical role of lysosomal dysfunction in the development of SIPS through the cathepsin-induced proteolytic cleavage of SIRT1, a mechanism linking cell stress to apoptosis and SIPS
22234173	The proposed mechanism of SIRT1 depletion in stress has all of the attributes of being a paradigm of SIPS of EPCs
22228303	We identified Sirt1 as a direct target of miR-138, -181a, and -181b, whereas DeltaNp63 expression was inhibited by miR-130b
22197555	SIRT1 prevents replicative senescence of normal human umbilical cord fibroblast through potentiating the transcription of human telomerase reverse transcriptase gene
22197555	SIRT1, the mammalian homolog of sirtuins, has emerged as a mediator of the beneficial effects of calorie restriction
22197555	Among them, we focused on the SIRT1-induced prevention of cellular senescence, and tried to reveal the molecular mechanisms that define the effects of SIRT1
22197555	Firstly in this study, we observed that overexpression of SIRT1 resulted in the prevention of cellular senescence of normal human umbilical cord fibroblast HUC-F2 cells
22197555	Results showed that SIRT1, SIRT1 activator, resveratrol, and SIRT1 activating condition, starved condition, increased the transcription of hTERT in HUC-F2 cells
22197555	Next, we found that SIRT1 increased hTERT transcription in a c-MYC-dependent manner, triggered the transcription of the c-MYC gene and increased the amount of c-MYC recruited to the hTERT promoter
22197555	Further, SIRT1 increased the transcriptional activation ability of c-MYC and correspondingly increased the amount of acetylated H4 histone at the hTERT promoter
22197555	All of these results indicated that SIRT1 activates hTERT transcription through the involvement of c-MYC, and suggested that this SIRT1-induced augmentation of hTERT transcription resulted in the extension of the cellular life span of HUC-F2 cells
22190494	The c-MYC oncoprotein, the NAMPT enzyme, the SIRT1-inhibitor DBC1, and the SIRT1 deacetylase form a positive feedback loop
22190494	Silent information regulator 1 (SIRT1) represents an NAD(+)-dependent deacetylase that inhibits proapoptotic factors including p53
22190494	Here we determined whether SIRT1 is downstream of the prototypic c-MYC oncogene, which is activated in the majority of tumors
22190494	Elevated expression of c-MYC in human colorectal cancer correlated with increased SIRT1 protein levels
22190494	Activation of a conditional c-MYC allele induced increased levels of SIRT1 protein, NAD(+), and nicotinamide-phosphoribosyltransferase (NAMPT) mRNA in several cell types
22190494	This increase in SIRT1 required the induction of the NAMPT gene by c-MYC
22190494	NAMPT is the rate-limiting enzyme of the NAD(+) salvage pathway and enhances SIRT1 activity by increasing the amount of NAD(+)
22190494	In primary human fibroblasts previously immortalized by introduction of c-MYC, down-regulation of SIRT1 induced senescence and apoptosis
22190494	In various cell lines inactivation of SIRT1 by RNA interference, chemical inhibitors, or ectopic DBC1 enhanced c-MYC-induced apoptosis
22190494	Furthermore, SIRT1 directly bound to and deacetylated c-MYC
22190494	Enforced SIRT1 expression increased and depletion/inhibition of SIRT1 reduced c-MYC stability
22190494	Depletion/inhibition of SIRT1 correlated with reduced lysine 63-linked polyubiquitination of c-Myc, which presumably destabilizes c-MYC by supporting degradative lysine 48-linked polyubiquitination
22190494	Moreover, SIRT1 enhanced the transcriptional activity of c-MYC
22190494	Taken together, these results show that c-MYC activates SIRT1, which in turn promotes c-MYC function
22178470	SIRT1 as a therapeutic target in inflammaging of the pulmonary disease
22178470	Sirtuin1 (SIRT1), a nicotinamide adenine dinucleotide (NAD(+))-dependent protein/histone deacetylase, regulates inflammation, senescence/aging, stress resistance, and deoxyribonucleic acid (DNA) damage repair via deacetylating intracellular signaling molecules and chromatin histones
22178470	The present review describes the mechanism and regulation of SIRT1 by environmental agents/oxidants/reactive aldehydes and pro-inflammatory stimuli in lung inflammation and aging
22178470	The role of dietary polyphenols in regulation of SIRT1 in inflammaging is also discussed
22178470	SIRT1 regulates inflammaging via regulating forkhead box class O 3, p53, nuclear factor kappa B, histones and various proteins involved in DNA damage and repair
22178470	Polyphenols and its analogs have been shown to activate SIRT1 although they have anti-inflammatory and antioxidant properties
22133824	Regulatory Mechanism of Mammalian Sirtuin SIRT1 in Vascular calcification: impact of vascular smooth muscle cell senescence]
22133824	Our new findings show that the senescent phenotypic change is associated with osteoblastic trans-differentiation in SMC and mammalian sirtuin SIRT1, which is well known as a longevity gene, can play an inhibitory role in the cellular senescence-related vascular calcification under hyperphosphatemia
22119379	Expression of SIRT1, which has attracted attention as an anti-aging factor in recent years, was significantly decreased in H(2)O(2)-exposed NHDF cells compared to untreated cells
22119379	However, pretreatment NHDF cells with AA-2G before H(2)O(2) exposure significantly inhibited this decrease in SIRT1 expression, whereas ascorbic acid had no effect
22038097	SIRT1 is required for long-term growth of human mesenchymal stem cells
22038097	In this study, we found that NAD-dependent protein deacetylase SIRT1 is differentially expressed in both human bone marrow-derived MSCs (B-MSCs) and adipose tissue-derived MSCs after increasing passages of cell culture
22038097	Using lentiviral shRNA we demonstrated that selective knockdown of SIRT1 in human MSCs at early passage slows down cell growth and accelerates cellular senescence
22038097	Conversely, overexpression of SIRT1 delays senescence in B-MSCs that have undergone prolonged in vitro culturing and the cells do not lose adipogenic and osteogenic potential
22038097	In addition, we found that the delayed accumulation of the protein p16 is involved in the effect of SIRT1
22038097	However, resveratrol, which has been used as an activator of SIRT1 deacetylase activity, only transiently promotes proliferation of B-MSCs
22038097	Our findings will help us understand the role of SIRT1 in the aging of normal diploid cells and may contribute to the prevention of human MSCs senescence thus benefiting MSCs-based tissue engineering and therapies
21968188	This acetylation event was suppressed by SIRT1 activation
21968188	CKIIalpha and CKIIbeta were co-immunoprecipitated with SIRT1 in a p53-independent manner
21968188	Maltose binding protein pull-down and yeast two-hybrid indicated that SIRT1 bound to CKIIbeta, but not to CKIIalpha
21968188	CKII inhibition reduced SIRT1 activity in cells
21968188	CKII phosphorylated and activated human SIRT1 in vitro
21968188	Finally, SIRT1 overexpression antagonized CKII inhibition-mediated cellular senescence
21968188	These results reveal that CKII downregulation induces p53 stabilization by negatively regulating SIRT1 deacetylase activity during senescence
25961265	Interestingly, also an inhibitor of SIRT1, a class HDAC III, induces cellular senescence
21909125	The expression levels of Sirt1 mRNA and protein were measured by RT-PCR and Western blot, respectively
21909125	RHL (5 and 10 mumol/L) enhanced both mRNA transcription and protein expression of Sirt1
21909125	H2O2 (100 mumol/L) significantly decreased Sirt1 expression, and induced up-regulation of p53 acetylation and p16(INK4a), which were blocked by pre-treatment with RHL (10 mumol/L)
21909125	Interference with siRNA for Sirt1 abolished the effect of RHL
21909125	CONCLUSION: RHL protected HUVECs against cellular senescence induced by H2O2, via up-regulation of Sirt1 expression and down-regulation of the expression of acetyl-p53 and p16(INK4a)
21861060	Silent information regulator 1 (SIRT1), an NAD(+)-dependent deacetylase, is involved in the regulation of gene transcription, energy metabolism and cell aging
21861060	Recent studies have showed that SIRT1 possesses neuroprotective effects, however, it is not very clear how SIRT1 exerts the neuroprotection in Alzheimer's disease (AD)
21861060	In this review, we summarized the neuroprotective role of SIRT1 in AD and its possible molecular mechanisms, proposing a novel strategy for preventing and treating neurodegeneration
21719763	Sirtuin 1 retards hyperphosphatemia-induced calcification of vascular smooth muscle cells
21719763	Recent studies have demonstrated that mammalian sirtuin 1 (SIRT1), a histone deacetylase, is an exciting target for cardiovascular disease management
21719763	Here, we investigated the role of SIRT1 in a calcification model of vascular smooth muscle cells (SMCs)
21719763	In cultured SMCs, inorganic phosphate (Pi) stimulation dose-dependently increased SAbeta-gal-positive cells, and Pi-induced senescence was associated with downregulation of SIRT1 expression, leading to p21 activation
21719763	The activation via SIRT1 downregulation was blunted by inhibition of Pi cotransporter
21719763	Activation of SIRT1 by resveratrol significantly reduced the senescence-associated calcification
21719763	Conversely, SIRT1 knockdown by small interfering RNA accelerated the Pi-induced SMC senescence and subsequent calcification
21719763	In addition, SIRT1 knockdown induced phenotypic change from a differentiated state to osteoblast-like cells
21719763	CONCLUSIONS: SIRT1 plays an essential role in preventing hyperphosphatemia-induced arterial calcification via inhibition of osteoblastic transdifferentiation
21549004	Mammalian Sirt1: insights on its biological functions
21549004	Sirt1 (member of the sirtuin family) is a nicotinamide adenosine dinucleotide (NAD)-dependent deacetylase that removes acetyl groups from various proteins
21549004	Sirt1 performs a wide variety of functions in biological systems
21549004	The current review focuses on the biological functions of Sirt1 in obesity-associated metabolic diseases, cancer, adipose tissue, aging, cellular senescence, cardiac aging and stress, prion-mediated neurodegeneration, inflammatory signaling in response to environmental stress, development and placental cell survival
21527554	Sirtuin 1 is upregulated in a subset of hepatocellular carcinomas where it is essential for telomere maintenance and tumor cell growth
21527554	Sirtuin 1 (SIRT1) is a class III histone deacetylase that is implicated in gene regulations and stress resistance
21527554	Downregulation of SIRT1 consistently suppressed the proliferation of HCC cells via the induction of cellular senescence or apoptosis
21527554	SIRT1 silencing also caused telomere dysfunction-induced foci and nuclear abnormality that were clearly associated with reduced expressions of telomerase reverse transcriptase (TERT), and PTOP, which is a member of the shelter in complex
21505241	Cloning, purification, crystallization and preliminary crystallographic analysis of the human histone deacetylase sirtuin 1
21505241	Human sirtuin 1 is a member of the histone deacetylase family and is involved in cellular aging, tumourigenesis and cellular metabolism
21505241	Recombinant sirtuin 1 comprising residues 140-747 was crystallized using the hanging-drop vapour-diffusion method
21497775	Silent information regulator 2 (Sir2/Sirt1), a member of the sirtuin family of class III histone deacetylases, has been implicated extensively in lifespan extension and is a prominent drug target in antiaging medicine
21497775	The mammalian Sirt1 has multiple targets, which include histones, transcription factors, and other molecules that collectively modulate energy metabolism, stress response, and cell/tissue survival
21497775	Several of Sirt1's substrates regulate key metabolic processes, and Sirt1 activation may underlie the lifespan prolonging effect of caloric restriction
21497775	Several studies also point towards a general tumor suppressive role for Sirt1, at least in the context of certain human cancers
21471201	Cancer cell survival following DNA damage-mediated premature senescence is regulated by mammalian target of rapamycin (mTOR)-dependent Inhibition of sirtuin 1
21471201	This process involved the mTOR-dependent phosphorylation of SIRT1 at serine 47, resulting in the inhibition of the deacetylase activity of SIRT1
21471201	SIRT1 phosphorylation caused concomitant increases in p65/RelA NF-kappaB acetylation and the expression of an anti-apoptotic Bfl-1/A1
21471201	SIRT1 physically interacts with the mTOR-Raptor complex, and a single amino acid substitution in the TOS (TOR signaling) motif in the SIRT1 prevented Ser-47 phosphorylation and Bfl-1/A1 induction
21471201	The pharmacologic and genetic inhibition of mTOR, unphosphorylatable S47A, or F474A TOS mutants restored SIRT1 deacetylase activity, blocked Bfl-1/A1 induction, and sensitized prematurely senescent SCC cells for apoptosis
21471201	These results demonstrate that the inhibition of SIRT1 by mTOR fosters survival of DNA damage-induced prematurely senescent SCC cells via Bfl-1/A1 in the absence of functional p53
21469181	E(2) had no regulatory effects on the expression rates of the cell cycle regulator p21 and the DNA repair proteins SIRT1 and XRCC5
21390332	GR resulted in an increased expression of SIRT1, a NAD-dependent histone deacetylase, which has positive correlation with CR-induced longevity
21390332	The elevated SIRT1 was accompanied by enhanced activation of the Akt/p70S6K1 signaling pathway in response to GR
21390332	Furthermore, knockdown of SIRT1 abolished GR-induced p16 repression as well as Akt/p70S6K1 activation implying that SIRT1 may affect p16 repression through direct deacetylation effects and indirect regulation of Akt/p70S6K1 signaling
21376036	SIRT1 and XRCC5 were up-regulated after oxidant insult and expression levels increased in aging cells
21284033	SIRT1 and XRCC5 enable cells to cope with unfavorable growing conditions
21190955	Aldosterone induced senescence-like changes in the kidney, exhibited by increased expression of the senescence-associated beta-galactosidase, overexpression of p53 and cyclin-dependent kinase inhibitor (p21), and decreased expression of SIRT1
21190955	Furthermore, aldosterone induced similar changes in senescence-associated beta-galactosidase, p21, and SIRT1 expression in cultured human proximal tubular cells, which were normalized by an antioxidant, N-acetyl L-cysteine, or gene silencing of MR
21169404	Mthfr deficiency induces endothelial progenitor cell senescence via uncoupling of eNOS and downregulation of SIRT1
21169404	Impaired differentiation of EPCs induced by Mthfr deficiency correlated with increased senescence, decreased telomere length, and reduced expression of SIRT1
21169404	Addition of sepiapterin maintained cell senescence and SIRT1 expression at levels comparable to the wild type
21169404	Taken together, these results demonstrate that Mthfr deficiency impairs EPC formation and increases EPC senescence by eNOS uncoupling and downregulation of SIRT1
21130086	The various signaling networks responsible for the anti-ageing and anti-senescence activity of SIRT1 have been discussed
21108727	Mechanistically, we find that both Ku and SIRT1 are induced during restoration and are required for senescent cells to return to a youthful phenotype
20829644	Among the sirtuin family proteins in mammals, the one most similar to yeast Sir2 is SIRT1, which is involved in multiple pathways, including the repair of DNA double-strand breaks
20829644	Although the role of SIRT1 in mammalian longevity is not clear, it is expressed throughout the retina, where it may suppress aging
20829644	In fact, a mutant mouse model of retinal degeneration shows an abnormal subcellular localization of SIRT1 protein and accelerated retinal cell apoptosis
20813124	High-affinity Na(+)-dependent dicarboxylate cotransporter promotes cellular senescence by inhibiting SIRT1
20813124	NAD(+)-dependent histone deacetylase sirtuin1 (SIRT1) prolongs mammalian cellular lifespan
20813124	Therefore, we propose that NaDC3 accelerates cellular aging by inhibiting SIRT1
20813124	Meanwhile, the level of SIRT1 activity was down-regulated
20813124	In WI38/hNaDC3 cells treated with the activators of SIRT1, aging-related phenotypes induced by NaDC3 were obviously improved
20813124	Thus, NaDC3 promotes cellular senescence probably by inhibiting NAD(+)-dependent SIRT1
20713685	VAT-EC had enhanced expression of the cellular senescence markers, IGFBP3 and gamma-H2AX, and decreased expression of SIRT1
20660480	SIRT1 is regulated by a PPAR{gamma}-SIRT1 negative feedback loop associated with senescence
20660480	Human Silent Information Regulator Type 1 (SIRT1) is an NAD(+)-dependent deacetylase protein which is an intermediary of cellular metabolism in gene silencing and aging
20660480	SIRT1 has been extensively investigated and shown to delay senescence; however, less is known about the regulation of SIRT1 during aging
20660480	In this study, we show that the peroxisome proliferator-activated receptor-gamma (PPARgamma), which is a ligand-regulated modular nuclear receptor that governs adipocyte differentiation and inhibits cellular proliferation, inhibits SIRT1 expression at the transcriptional level
20660480	Moreover, both PPARgamma and SIRT1 can bind the SIRT1 promoter
20660480	PPARgamma directly interacts with SIRT1 and inhibits SIRT1 activity, forming a negative feedback and self-regulation loop
20660480	These results demonstrate a mutual regulation between PPARgamma and SIRT1 and identify a new posttranslational modification that affects cellular senescence
20627091	Searching for how miR-34a affects senescence, we discovered that SIRT1 is a target of miR-34a
20627091	Over-expressing miR-34a inhibits SIRT1 protein expression, and knocking down miR-34a enhances SIRT1 expression
20627091	MiR-34a triggers endothelial senescence in part through SIRT1, since forced expression of SIRT1 blocks the ability of miR-34a to induce senescence
20627091	Our data suggest that miR-34a contributes to endothelial senescence through suppression of SIRT1
20488443	Sirt1 plays an important role in mediating greater functionality of human ES/iPS-derived vascular endothelial cells
20488443	We then analyzed the gene expressions of HAECs, ESECs and iPSECs, and observed that the expression level of Sirt1, a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase, is higher in ESECs and iPSECs than in HAECs
20488443	The inhibition of Sirt1 with a Sirt1-specific inhibitor and siRNA antagonized these differences between the three types of cells
20488443	CONCLUSIONS: Sirt1 plays a key role in the high cellular function of ESECs and iPSECs
20450879	Sirtuin 1 (SIRT1) is known to deacetylate histones and non-histone proteins including transcription factors thereby regulating metabolism, stress resistance, cellular survival, cellular senescence/aging, inflammation-immune function, endothelial functions, and circadian rhythms
20450879	In addition, these polyphenols have also been shown to activate SIRT1 directly or indirectly in a variety of models
20450879	Therefore, activation of SIRT1 by polyphenols is beneficial for regulation of calorie restriction, oxidative stress, inflammation, cellular senescence, autophagy/apoptosis, autoimmunity, metabolism, adipogenesis, circadian rhythm, skeletal muscle function, mitochondria biogenesis and endothelial dysfunction
20450879	In this review, we describe the regulation of SIRT1 by dietary polyphenols in various cellular functions in response to environmental and pro-inflammatory stimuli
20424141	MiR-34a, recently reported as a tumor suppressor, has been found to target silent information regulator 1 (Sirt1), leading to cell cycle arrest or apoptosis
20424141	The present study tested the hypothesis that miR-34a inhibits EPC-mediated angiogenesis by inducing senescence via suppressing Sirt1
20424141	MiR-34a overexpression led to a significantly increased EPC senescence, paralleled with an approximately 40% Sirt1 reduction
20424141	Furthermore, knockdown of Sirt1 by its siRNA resulted in diminished EPC angiogenesis and increased senescence
20424141	Finally, overexpression of miR-34a increased the level of Sirt1 effector-acetylated forkhead box O transcription factors 1 (FoxO1), an effect mimicked in EPCs following Sirt1 knockdown
20424141	In conclusion, miR-34a impairs EPC-mediated angiogenesis by induction of senescence via inhibiting Sirt1
20224429	In addition, the increase in levels of intracellular reactive oxygen species and downregulation of SIRT1 gene expression induced by homocysteine were significantly reversed by selaginellin
20224429	Our study suggests that selaginellin has a protective effect against homocysteine-induced senescence through mechanisms related to antioxidation via scavenging reactive oxygen species and upregulating the expression of SIRT1 gene
20203304	SIRT1 promotes proliferation and prevents senescence through targeting LKB1 in primary porcine aortic endothelial cells
20203304	SIRT1 is a conserved NAD(+)-dependent deacetylase possessing beneficial effects against aging-related diseases, despite that the detailed functional mechanisms are largely uncharacterized
20203304	OBJECTIVE: The present study is designed to evaluate the protective effects of SIRT1 on endothelial senescence and to elucidate the underlying mechanisms
20203304	Both mRNA and protein expressions of SIRT1 were progressively decreased
20203304	Overexpression of LKB1 promoted cellular senescence and retarded endothelial proliferation, which could be blocked by increasing SIRT1 levels
20203304	Knocking down of SIRT1 induced senescence and elevated the protein levels of LKB1 and phosphorylated AMPK(Thr172)
20203304	CONCLUSIONS: SIRT1 and LKB1/AMPK are the 2 key sensor systems for regulating endothelial cell survival, proliferation and senescence
20203304	The protective activities of SIRT1 may be achieved at least in part by fine tuning the acetylation/deacetylation status and stabilities of LKB1 protein
20157516	Anti-aging protein SIRT1: a role in cervical cancer
20132235	The beneficial effects of BTM-0512 on high glucose-induced senescence were blocked by splimtomicin, the specific inhibitor of SIRT1, or by silencing DDAH2 expression
20078953	As the most homologic homologue of silent information regulator 2 of yeast, Sirt1 gene is extensively expressed in mature tissues, and is rich in early embryo and reproductive cells
20078953	Furthermore, Sirt1 gene is an essential endogenous apoptosis inhibitor
27713233	However, in recent years it has been demonstrated that the families of enzymes called sirtuins, specifically situin 1 (SIRT1), have an anti-aging action
27713233	Thus, the natural compound resveratrol is a natural compound that shows a very strong activation of SIRT1 and also shows antioxidant effects
19887452	Overexpression or activation of SIRT1 significantly reduces the IR-induced senescence phenotype, whereas inhibition of SIRT1 activity induces senescence
19833096	Red wine decreases asymmetric dimethylarginine via SIRT1 induction in human endothelial cells
19833096	Blockade of SIRT1 activity abolished the effect of red wine on ADMA
19833096	These data are the first demonstration that RW by activating SIRT1 impairs synthesis and increases metabolism of ADMA
19818845	Here we review such roles and discuss the entangled relationships between HDAC1 with histone acetyltransferases and other HDACs including SIRT1
19786632	METHODS AND RESULTS: miR-217 inhibits SirT1 expression through a miR-217-binding site within the 3'-UTR of SirT1
19786632	In young human umbilical vein endothelial cells, human aortic endothelial cells, and human coronary artery endothelial cells, miR-217 induces a premature senescence-like phenotype and leads to an impairment in angiogenesis via inhibition of SirT1 and modulation of FoxO1 (forkhead box O1) and endothelial nitric oxide synthase acetylation
19786632	Conversely, inhibition of miR-217 in old endothelial cells ultimately reduces senescence and increases angiogenic activity via an increase in SirT1
19786632	CONCLUSIONS: Our data pinpoint miR-217 as an endogenous inhibitor of SirT1, which promotes endothelial senescence and is potentially amenable to therapeutic manipulation for prevention of endothelial dysfunction in metabolic disorders
19625699	Sirtuin 1
19520256	Sirolimus and everolimus induce endothelial cellular senescence via sirtuin 1 down-regulation: therapeutic implication of cilostazol after drug-eluting stent implantation
19520256	OBJECTIVES: The aim of this study was to compare the effects of paclitaxel, sirolimus, and everolimus on the senescent phenotype in human endothelial cells, and to further investigate possible involvement of mammalian sirtuin 1 (Sirt1) down-regulation as a mechanism
19520256	Recently, the down-regulation of Sirt1 has been shown to mediate oxidative stress-induced endothelial senescence
19520256	RESULTS: Treatment with paclitaxel, sirolimus, and everolimus significantly caused a senescent phenotype and PAI-1 up-regulation, associated with a decrease in endothelial nitric oxide synthase (eNOS) and Sirt1 expression
19520256	Overexpression of Sirt1 or Sirt1 activation reversed the sirolimus- or everolimus-induced senescent phenotype
19520256	Interestingly, paclitaxel-induced senescence was not suppressed by Sirt1 overexpression, suggesting the existence of a different mechanism
19520256	CONCLUSIONS: Sirolimus and everolimus induce endothelial senescence involving down-regulation of Sirt1
19520256	Because sirolimus and everolimus are involved in Sirt1 modulation, cilostazol rescues HUVEC from sirolimus- or everolimus-induced senescence
19439501	SIRT1 controls circadian clock circuitry and promotes cell survival: a connection with age-related neoplasms
19439501	SIRT1, a nicotinamide adenine dinucleotide (NAD(+))-dependent sirtuin, has been shown to promote cell survival by inhibiting apoptosis or cellular senescence in mammalian cells
19439501	Recent studies have provided a link between the cellular metabolic function of SIRT1 and the circadian rhythm (controlled by a clock machinery), which, if deregulated, may lead to an increased risk for some cancers
19439501	On the basis of scientific evidence, we propose a hypothesis that SIRT1 inhibition will impart an antiproliferative response in age-related cancers via resynchronization of deregulated core clock circuitry at the cellular level
19318942	Molecular analyses identified the role of sirtuin 1 in preventing cell senescence; shed light on the role of polycomb group (PcG) protein Bmi-1 in senescence
19286634	Protective role of SIRT1 in diabetic vascular dysfunction
19286634	SIRT1, a mammalian homolog of Sir2, has been reported to downregulate p53 activity and thereby prolong the lifespan of cells
19286634	Although recent evidence suggests a link between SIRT1 activity and metabolic homeostasis during CR, its pathological role in human disease is not yet fully understood
19286634	METHODS AND RESULTS: Treatment of human endothelial cells with high glucose decreases SIRT1 expression and thus activates p53 by increasing its acetylation
19286634	Introduction of SIRT1 or disruption of p53 inhibits high glucose-induced endothelial senescence and dysfunction
19286634	Likewise, activation of Sirt1 prevents the hyperglycemia-induced vascular cell senescence and thereby protects against vascular dysfunction in mice with diabetes
19286634	CONCLUSIONS: These findings represent a novel mechanism of vascular cell senescence induced by hyperglycemia and suggest a protective role of SIRT1 in the pathogenesis of diabetic vasculopathy
19221490	MiR-34, SIRT1 and p53: the feedback loop
19221490	We recently found that miR-34a inhibits SIRT1, a gene that regulates cellular senescence and limits longevity
19221490	SIRT1 also regulates p53 dependent apoptosis through deacetylating and stabilizing p53
19221490	Based on this observation, we propose a positive feedback loop, in which p53 induces expression of miR-34a which suppresses SIRT1, increasing p53 activity
18797187	Sirt1, notch and stem cell "age asymmetry"
18797187	The protein-deacetylase, SIRT1, has received much attention because of its roles in oxygen metabolism, cellular stress response, aging, and has been investigated in various species and cell types including embryonic stem cells
18797187	However, there is a dearth of information on SIRT1 in adult stem cells, which have a pivotal role in adult aging processes
18797187	Here, we discuss the potential relationships between SIRT1 and the surface receptor protein, Notch, with stem cell self-renewal, asymmetric cell division, signaling and stem cell aging
18638538	Our recent results also provide evidence for a role of the mammalian Sir2 ortholog SirT1 in the activation of a highly conserved neuronal pathway and in the sensitization of neurons to oxidative damage
18638538	However, the mean lifespan of the SirT1(+/-) mice is not different from that of wild type animals, and the survival of SirT1(-/-) mice was reduced under both normal and calorie restricted conditions
18638538	Here, I review the studies linking SirT1, IGF-I signaling and starvation in various model organisms with a focus on the post-mitotic cells, which indicate that sirtuins can play both protective and pro-aging roles
18536570	Sirtuin 1, stem cells, aging, and stem cell aging
18536570	We consider recent information on sirtuin 1, its role in aging and metabolism in several species and tissues, and attempt to anticipate how it might influence stem cell aging
18536570	Recent work indicates that sirtuin 1 influences growth-factor responses and maintenance of stem cells
18536570	Sirtuin 1 is required for calorie restriction-induced lifespan extension in mice, and calorie restriction upregulates sirtuin 1 in humans
18536570	Sirtuin 1 also appears to influence lineage/cell-fate decisions of stem cells via redox status
18520066	Among homologs of the silent information regulator (Sir), sirtuin 1 (SIRT1) is suggested as a regulator of the apoptotic response to DNA damage
18520066	Since it has been suggested that the aging process can be delayed by the attenuation of oxidative damage such as DNA damage or SIRT1 modulation, we focused on the protective effect against cellular oxidative damage of persimmon peel, a proanthocyanidin-rich food, in relation to its level of polymerization
18520066	On the other hand, the nuclear SIRT1 level was decreased in H2O2-treated as compared with non-pretreated cells
18520066	However, pretreatments with polymers and oligomers led to a decrease in 8-OHdG and elevation in nuclear SIRT1 expression in a concentration-dependent manner
18369446	1/SIRT1 and lagr-1/LASS2
18320031	SIRT1 overexpression antagonizes cellular senescence with activated ERK/S6k1 signaling in human diploid fibroblasts
18320031	The SIRT1, mammalian homologue of Sir2, regulates signaling for favoring survival in stress
18320031	But whether SIRT1 has the function to influence cell viability and senescence under non-stressed conditions in human diploid fibroblasts is far from unknown
18320031	Our data showed that enforced SIRT1 expression promoted cell proliferation and antagonized cellular senescence with the characteristic features of delayed Senescence-Associated beta-galactosidase (SA-beta-gal) staining, reduced Senescence-Associated Heterochromatic Foci (SAHF) formation and G1 phase arrest, increased cell growth rate and extended cellular lifespan in human fibroblasts, while dominant-negative SIRT1 allele (H363Y) did not significantly affect cell growth and senescence but displayed a bit decreased lifespan
18320031	Western blot results showed that SIRT1 reduced the expression of p16(INK4A) and promoted phosphorylation of Rb
18320031	Our data also exposed that overexpression of SIRT1 was accompanied by enhanced activation of ERK and S6K1 signaling
18320031	These effects were mimicked in both WI38 cells and 2BS cells by concentration-dependent resveratrol, a SIRT1 activator
18320031	It was noted that treatment of SIRT1-
18320031	It was also observed that the expression of SIRT1 and phosphorylation of ERK and S6K1 was declined in senescent 2BS
18203716	Mammalian Sir2 (SIRT1) has also been found to regulate premature cellular senescence induced by the tumor suppressors PML and p53
18203716	SIRT1 plays an important role in cell survival promoted by calorie restriction
18203716	Here we show that SIRT1 interacts with WRN both in vitro and in vivo; this interaction is enhanced after DNA damage
18203716	WRN acetylation decreases its helicase and exonuclease activities, and SIRT1 can reverse this effect
18203716	Down-regulation of SIRT1 reduces WRN translocation from nucleoplasm to nucleoli after DNA damage
18193082	SIRT1 negatively regulates HDAC1-dependent transcriptional repression by the RBP1 family of proteins
18193082	Further work uncovered an interaction between RBP1 family proteins and the mammalian homologue of SIR2, SIRT1
18193082	Interestingly, the HDAC-dependent transcriptional repression domain of RBP1 proteins, termed R2, is necessary and sufficient for the interaction with SIRT1
18193082	In vitro and in vivo binding studies indicated that the p33(ING1b) and p33(ING2) subunits of the mSIN3A/HDAC1 complex are responsible for the recruitment of SIRT1 to the R2 domain
18193082	To investigate the biological relevance of this interaction, we used the sirtuin activator resveratrol and the sirtuin inhibitor sirtinol in transcriptional repression assays and demonstrated that SIRT1 activity negatively regulates R2-mediated transcriptional repression activity
18193082	Explicitly, SIRT1 is recruited by ING proteins and inhibits R2-associated mSIN3A/HDAC1 transcriptional repression activity
17996922	Expression and localization of Werner syndrome protein is modulated by SIRT1 and PML
17996922	Interestingly, mRFP-WRN relocalizes from nucleoli to the nucleoplasm, frequently showing conspicuous nucleolar exclusion as well as a decrease in frequency of mRFP-WRN nuclear bodies in response to overexpression of wild-type and deacetylase mutant (H363Y) SIRT1 proteins
17996922	Similar nucleolar relocalization in response to wild-type SIRT1 was detected for mRFP-labeled BLM
17996922	Moreover, increased SIRT1 expression was associated with the downregulation of endogenous WRN and a decreased frequency of cells with BRCA1 foci
17996922	Our data indicate for the first time that SIRT1 protein may be functionally associated with WRN and BLM helicases and that some major SIRT1 functions may not require its deacetylase activity
17916362	Sirt1 modulates premature senescence-like phenotype in human endothelial cells
17916362	Mammalian Sirt1 NAD(+)-dependent protein deacetylase, the closest homolog of Sir2, regulates cell cycle, cellular senescence, apoptosis and metabolism, by functional interactions with a number of biological molecules such as p53
17916362	To investigate a role of Sirt1 in endothelial dysfunction and premature senescence, we examined the effects of Sirt1 inhibition in human umbilical vein endothelial cells (HUVEC)
17916362	Sirt1 inhibition by sirtinol, which is a 2-hydroxy-1-napthaldehyde derivative, or siRNA for Sirt1-induced premature senescence-like phenotype, as judged by increased senescence-associated beta-galactosidase (SA-beta-gal) activity, sustained growth arrest and enlarged and flattened cell morphology at 10 days after the treatment
17916362	Sirt1 inhibition by sirtinol or Sirt1 siRNA increased PAI-1 expression and decreased both protein expression and activity of eNOS
17916362	Treatment with sirtinol or Sirt1 siRNA increased acetylation of p53, while p53 expression was unaltered
17916362	Impaired epidermal growth factor-induced activation of mitogen-activated protein kinases was associated with Sirt1 inhibition-induced senescence-like growth arrest
17916362	Conversely, overexpression of Sirt1 prevented hydrogen peroxide-induced SA-beta-gal activity, morphological changes and deranged expression of PAI-1 and eNOS
17916362	These results showed that Sirt1 inhibition increased p53 acetylation and induced premature senescence-like phenotype in parallel with increased PAI-1 and decreased eNOS expression
17916362	Our data suggest that Sirt1 may exert protective effects against endothelial dysfunction by preventing stress-induced premature senescence and deranged expression of PAI-1 and eNOS
17691205	METHODS: Silent mating type information regulation 2 homolog 1 (SIRT1) was investigated by immunostaining, Westem blotting, and cytometry on normal human skin cells in culture and on healthy skin samples ex vivo
17691205	Subjects applied a formulation enriched in 1% of the yeast biopeptides SIRT1 activator once daily to the face and neck for 4 weeks
17691205	RESULTS: The yeast Kluyveromyces biopeptides 1) significantly increased SIRT1 expression in normal human dermal skin fibroblasts in vitro (+172%) and in epidermal cells of healthy human skin ex vivo and 2) decreased cell senescence and DNA fragmentation induced by ultraviolet-B (UVB) stress
17595514	H2O2 accelerates cellular senescence by accumulation of acetylated p53 via decrease in the function of SIRT1 by NAD+ depletion
17595514	It has been reported that p53 acetylation, which promotes cellular senescence, can be regulated by the NAD(+)-dependent deacetylase SIRT1, the human homolog of yeast Sir2, a protein that modulates lifespan
17595514	To clarify the role of SIRT1 in cellular senescence induced by oxidative stress, we treated normal human diploid fibroblast TIG-3 cells with H(2)O(2) and examined DNA cleavage, depletion of intracellular NAD(+), expression of p21, SIRT1, and acetylated p53, cell cycle arrest, and senescence-associated beta-galactosidase (SA-beta-gal) activity
17595514	The amount of acetylated p53 was increased in TIG-3 cells at 4h after H(2)O(2) treatment, while there was little to no decrease in SIRT1 protein expression
17433727	Human SIRT1: a potential biomarker for tumorigenesis
17433727	Accumulating body of evidence reveals that hSIRT1, an NAD(+)-dependent protein deacetylase, is involved in regulating numerous biological processes
17433727	Therefore cellular functions of hSIRT1 are highly pleiotropic
17433727	The integrated hypothetical mechanisms of hSIRT1 action contributing to regulating cellular senescence and longevity have been proposed
17433727	Based on recent evidence, I propose that hSIRT1 is a potential biomarker for tumorigenesis
16940753	DeltaNp63alpha overexpression induces downregulation of Sirt1 and an accelerated aging phenotype in the mouse
16940753	We found that aging in deltaNp63alpha transgenic mice and other mouse models correlated with levels of Sirt1, a mammalian SIR2 orthologue thought to extend the lifespan in lower species
16940753	Moreover, increased deltaNp63alpha expression induced cellular senescence that was rescued by Sirt1
16940753	Our data suggest that deltaNp63alpha levels may affect aging in mammals, at least in part, through regulation of Sirt1
16546327	SIRT1: tumor promoter or tumor suppressor
16546327	The demonstrated roles of SIRT1, the mammalian counterpart of the yeast SIR2, reveal that SIRT1 regulates important cellular processes including anti-apoptosis, neuronal protection, cellular senescence, aging and longevity
16546327	Based on the observations that SIRT1 is upregulated in tumor cells, the hypothesis is that deregulation of SIRT1 expression may promote tumorigenesis by altering cellular signaling or by inducing modulation of chromatin remodeling leading to promotion of tumorigenesis
16546327	Further studies will shed new light on the underlying mechanisms of tumorigenesis mediated by SIRT1
16170353	Sirt1 inhibitor, Sirtinol, induces senescence-like growth arrest with attenuated Ras-MAPK signaling in human cancer cells
16170353	However, a potential antiproliferative effect of inhibitor for Sirt1, which is an NAD(+)-dependent deacetylase and belongs to class III histone deacetylases, has not yet been explored
16170353	Here, we show that Sirt1 inhibitor, Sirtinol, induced senescence-like growth arrest characterized by induction of senescence-associated beta-galactosidase activity and increased expression of plasminogen activator inhibitor 1 in human breast cancer MCF-7 cells and lung cancer H1299 cells
16170353	These results suggest that inhibitors for Sirt1 may have anticancer potential, and that impaired activation of Ras-MAPK pathway might take part in a senescence-like growth arrest program induced by Sirtinol
15171255	Subsequent work has also identified Sir2alpha, a NAD-dependent histone deacetylase that can attenuate p53 transcriptional activity through deacetylation
15171255	We present data indicating that both HDAC1 and Sir2alpha are critical for p53-dependent stress response
15171255	Finally, we propose a model regarding the differential roles of HDAC1 and Sir2alpha in the regulation of p53 function
12960381	SIRT1 is a mammalian homolog of the Saccharomyces cerevisiae chromatin silencing factor Sir2
12960381	Dominant-negative and overexpression studies have implicated a role for SIRT1 in deacetylating the p53 tumor suppressor protein to dampen apoptotic and cellular senescence pathways
12960381	To elucidate SIRT1 function in normal cells, we used gene-targeted mutation to generate mice that express either a mutant SIRT1 protein that lacks part of the catalytic domain or has no detectable SIRT1 protein at all
12960381	Both types of SIRT1 mutant mice and cells had essentially the same phenotypes
12960381	SIRT1 mutant mice were small, and exhibited notable developmental defects of the retina and heart, and only infrequently survived postnatally
12960381	Together, our observations provide direct evidence that endogenous SIRT1 protein regulates p53 acetylation and p53-dependent apoptosis, and show that the function of this enzyme is required for specific developmental processes
12220851	However, several recent studies have now determined a remarkable function for the human SIRT1 protein, which is the closest human homolog of yeast Sir2
12220851	SIRT1 specifically associates with the p53 tumor suppressor protein and deacetylates it, resulting in negative regulation of p53-mediated transcriptional activation
12220851	Importantly, p53 deacetylation by SIRT1 also prevents cellular senescence and apoptosis induced by DNA damage and stress
12006491	Here, we show that SIRT1, the human Sir2 homolog, is recruited to the promyelocytic leukemia protein (PML) nuclear bodies of mammalian cells upon overexpression of either PML or oncogenic Ras (Ha-rasV12)
12006491	SIRT1 binds and deacetylates p53, a component of PML nuclear bodies, and it can repress p53-mediated transactivation
12006491	Moreover, we show that SIRT1 and p53 co-localize in nuclear bodies upon PML upregulation
12006491	When overexpressed in primary mouse embryo fibroblasts (MEFs), SIRT1 antagonizes PML-induced acetylation of p53 and rescues PML-mediated premature cellular senescence
12006491	Taken together, our data establish the SIRT1 deacetylase as a novel negative regulator of p53 function capable of modulating cellular senescence

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HCSGD entry for SIRT1

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MiRNA mature ID

Test method inter

MiRNA regulation site

Reporter target site

Pubmed ID

6. Text-mining results about the gene

Gene occurances in abstracts of cellular senescence-associated articles: 192 abstracts the gene occurs.

PubMed ID of the article

Sentenece the gene occurs

Navigator

Individual experiment result
( "-" represent NA in the specific microarray platform )