Venkatachalam/aging_reg_dataset · Datasets at Hugging Face

SLC16A7

9194

protein coding

LoVo,HT29,HCT-8,HCT116,SW480 ,MKN45,MKN74

--

Colorectal cancer

Prevent

Cell morphological analysis//Immunostaining//SA--gal activity assay//SAHF

All the cancer cell lines examined, including those of the colon (HCT8, HCT116, HT29, LoVo, and SW480) and stomach (MKN45 and MKN74), displayed cellular enlargement and flattening as well as positivity for SA-¦Â-Gal staining, following knockdown of MCT2. Cells additionally exhibited senescence-associated nuclear proper...

--

Human

L

delay aging

22,964,484

Gene

0

1

0

1

0

1

0

1

0

FIS1

51024

protein coding

Chang

--

Aging

Prevent

Cell counting//Knockdown//SA--gal activity assay//XTT assay

The hFis1 knockdown cells started becoming progressively flattened on day 2 and were obviously flattened and enlarged on day 4, showing a phenotype similar to that of cells undergoing senescence. On days 4 and 5,~30% of the hFis1 RNAi cells stained positive for senescence-associated ¦Â-galactosidase , whereas no staini...

OPA1

--

SA-¦Â-gal activity assay//Knockdown//Flow cytometry//Immunostaining

Furthermore, hFis1 and OPA1 double-knockdown cells showed significant decreases in positive senescence-associated ¦Â-galactosidase staining as well as in cellular granularity.We found that prolonged depletion of hFis1 in fact increased ROS production on day 4. Moreover, sustained depletion of hFis1 caused a significant...

--

Human

L

delay aging

17,545,159

Gene

0

1

0

1

0

1

0

1

0

NFKB2

4791

protein coding

A375

--

Melanoma

Prevent

Flow cytometry//SA--gal activity assay//Western blot//qRT-PCR

Cell size and granularity as determined by flow cytometry were significantly increased, as were the senescenceassociated ¦Â-galactosidase (SA-¦Â-Gal) activity and HP1¦Ã expression.The mRNA levels of p16 and p21 were increased after NF-kB2 silencing.

EZH2//NIK

Upregulation//--

qRT-PCR//Western blot

Using quantitative realtime PCR (qRT-PCR) in A375 melanoma cells, we observed a marked decrease in EZH2 mRNA under treatment with these NF-kB inhibitors.Similar to NF-kB2 silencing, NIK silencing strongly decreased the total NF-kB activity and abolished EZH2 promoter transcriptional activity. NF-kB2 overexpression (ref...

--

Human

L

delay aging

26,364,600

Gene

0

1

0

1

0

1

0

1

0

CAV1

857

protein coding

MEF

--

Aging

Accelerate

Cell morphological analysis//SA--gal activity assay

A higher percentage of caveolin-1-overexpressing MEFs (passage 1) are positive for acid ¦Â-galactosidase enzymatic activity as compared with MEFs derived from normal control mice.Light microscopy experiments indicated that 70¡À5% of MEFs(passage 1; n = 20) overexpressing caveolin-1 show a large and flat morphology as c...

--

Human

L

delay aging

12,134,086

Gene

0

1

0

1

0

MIF

4282

protein coding

MSC

--

Aging

Prevent

Cell counting//MTT assay//qRT-PCR

The present study identified that 100 ng/ml MIF pretreatment in the presence of DOXO significantly increased MSC proliferation and cell viability compared with the DOXO group.Furthermore, MIF treatment significantly increased telomere length and restored telomerase activity, which were decreased by exposure to DOXO.

--

PI3K-Akt

Activation

Western blot

Compared with the control group, treatment with DOXO at a concentration of 5 mol/l significantly decreased the phosphorylation of Akt, which was restored by MIF.

Human

L

delay aging

29,207,187

Gene

0

1

0

1

0

1

0

SIRT6

51548

protein coding

HuH-7,Hep3B

--

Hepatocellular carcinoma

Prevent

Cell morphological analysis//SA--gal activity assay//qRT-PCR

SIRT6-silenced cells were flattened and larger with the characteristic morphology of cellular senescence[17]. The percentages of SIRT6-depleted HCC cells positively stained with SA-¦Â-gal were 29.1 4.9% (shSIRT6-1) and 16.2 8.4% (shSIRT6-3) Hep3B cells and 29.3 5.2% (shSIRT6-1) and 17.1 6.3% (shSIRT6-1) Huh-7 cells, wh...

--

Human

HL

delay aging

27,824,900

Gene

0

1

0

1

0

1

0

CDK1

983

protein coding

RPE,U2OS

--

Aging

Accelerate

Immunostaining//SA--gal activity assay//SAHF

While long-term treatment with RO-3306 and NU6140 was toxic for cells, we found that all these markers were reduced upon combined Cdk1/2 RNAi or addition of Roscovitine, indicating that Cdk activity stimulates senescence.

p21

Upregulation

Western blot

p21 induction was reduced upon Cdk inhibition or depletion, suggesting that the remaining Cdk activity during a DDR promotes p21 expression.

--

Human

L

delay aging

28,345,297

Gene

0

1

0

1

0

1

0

CDK2

1017

protein coding

RPE,U2OS

--

Aging

Accelerate

Immunostaining//SA--gal activity assay//SAHF

While long-term treatment with RO-3306 and NU6140 was toxic for cells, we found that all these markers were reduced upon combined Cdk1/2 RNAi or addition of Roscovitine, indicating that Cdk activity stimulates senescence.

p21

Upregulation

Western blot

p21 induction was reduced upon Cdk inhibition or depletion, suggesting that the remaining Cdk activity during a DDR promotes p21 expression.

--

Human

L

delay aging

28,345,297

Gene

0

1

0

1

0

1

0

PRMT1

3276

protein coding

MCF-7,MDA-MB-231

--

Breast cancer

Prevent

BrdU assay//Knockdown//SA--gal activity assay//Western blot//qRT-PCR

The results revealed that both MDA-MB-231-shPRMT1 and MCF7-shPRMT1 cells showed a remarkably intensified SA-¦Â-gal staining.Also, depletion of PRMT1 significantly increased the p21 expression, and reduced the CDC2, CCNB1 and CCNA2 expression at both mRNA and protein levels, in contrast to the control cells. Moreover, B...

ZEB1

Activation

qRT-PCR//Western blot//CHIP

We found that only the ZEB1 expression was dramatically increased at both mRNA and protein levels, while the levels of other EMT inducers such as Twist, Snail and Slug, remained basically unchanged in MCF10A-PRMT1 cells. The results of quantitative chromatin immunoprecipitation (qChIP) assay revealed a prominent elevat...

--

Human

L

delay aging

26,813,495

Gene

0

1

0

1

0

1

0

1

0

1

0

KDR

3791

protein coding

--

Colon

Colitis associated cancer

Prevent

Immunostaining//SA--gal activity assay//Western blot

Specifically, senescence-associated beta-galactosidase (S-¦Â-Gal) and the cyclin-dependent kinase inhibitor p16INK4A, were significantly upregulated in tumors of VEGFR2 IEC mice compared to controls.Altered tissue of VEGFR2?IEC mice revealed stronger expression of ¦ÃH2A.X when compared to control mice using WB and IHC ...

p21

--

Immunostaining//Western blot

We observed a significant difference in p21 protein expression in tumors of VEGFR2-deficient mice compared to control mice, as assessed by Western blotting and IHC.Moreover, not only the overall concentration of p21 was distinctively upregulated in tumors of VEGFR2 IEC mice, but also a predominant nuclear staining patt...

PI3K-Akt

--

Co-IP

Using co-immunoprecipitation we were able to show an interaction of VEGFR2 and PI3K as well as AKT and p21, consistent with the idea of a functional connection of these molecules.

Human

L

delay aging

25,797,700

Gene

0

1

0

1

0

1

0

MYC

4609

protein coding

--

Liver,Lymphoma

Cancer

Prevent

SA--gal activity assay

The suppression of MYC in primary MYC-induced lymphoma and hepatocellular carcinoma resulted in senescence-associated acidic ¦Â-gal (SA-¦Â-Gal) staining.

p15INK4b//p21CIP

--//--

qRT-PCR

Among them, p15INK4b and p21CIP have been shown to be MYC targets.Upon MYC inactivation in vitro,osteosarcoma cell lines exhibited the induction of p15INK4b and p21CIP mRNA expression by quantitative RT-PCR.

--

Human

L

delay aging

17,664,422

Gene

0

1

0

BRCA1

672

protein coding

MEC

--

Breast cancer

Prevent

Cell morphological analysis//SA--gal activity assay

We observed that Brca1MGKO MECs exhibited a large and flattened shape, a typical morphology of cellular senescence, while MECs from the other genotypes of mice were smaller and spindle-shaped. Notably, most Brca1MGKO MECs exhibited strong, peri-nuclear staining of SA-¦Â-gal whereas only a small population of WT MECs an...

p16

--

Immunostaining//SA-¦Â-gal activity assay//BrdU assay//Flow cytometry

We found that the percentages of Ki67-positive MECs in p16 -/- and p16 -/- ;Brca1MGKO mice (24.28¡À2.1 and 24.06¡À4.3) were significantly higher than those in WT mice (6.39¡À1.3), which in turn were significantly higher than the percentage in Brca1MGKO (2.20¡À0.2) mice. Notably, most Brca1MGKO MECs exhibited strong, pe...

--

Human

L

delay aging

27,811,360

Gene

0

1

0

1

0

IGF1

3479

protein coding

Aortic endothelial cell

--

Atherosclerosis

Prevent

SA--gal activity assay

Incubation with 100 ng/mL IGF-1 for 24 h prior to hydrogen peroxide exposure significantly reduced expression of ¦Â-galactosidase activity, indicating that the enhanced antioxidant activity in response to IGF-1 counteracted oxidative stress induced premature cell senescence.

GPX1

Upregulation

Western blot//Enzyme activity assay//Immunostaining

Conversely£¬glutathione peroxidase (GPX) activity was upregulated in a dose-dependent and time-dependent manner.We further assessed GPX1 and GPX4 expressions by Western blot analysis. IGF-1 upregulated GPX1 (2.6-fold increase, 100 ng/mL IGF-1 vs 0 ng/mL IGF-1).Pre-exposure to IGF-1 dose-dependently suppressed ROS level...

PI3K

--

Western blot//GPX activity assay

The phosphatidylinositide 3-kinase (PI3k) inhibitor, LY294002, significantly suppressed IGF-1 upregulation of GPX1. IGF-1 upregulation of GPX activity was also significantly suppressed by LY294002 but not by PD98059 or SB202190, confirming that IGF-1 regulation of GPX was PI3k dependent.

Human

L

delay aging

23,261,989

Gene

0

1

0

TERT

7015

protein coding

GBM

--

Ataxia telangiectasia

Prevent

BrdU assay//Cell counting//SA--gal activity assay//TRF assay

The TRF assay showed that the telomere length of AT/TERT cells was extended to £¾12 kb, compared with ~4¨C11 kb for parental AT cells.Whereas parental AT cells underwent replicative senescence after ~24 PDs, AT/TERT cells survived for £¾70 to 100 PDs.

--

Human

L

delay aging

14,570,874

Gene

0

1

0

1

0

1

0

1

0

SOX5

6660

protein coding

GBM

Brain

Glioblastoma

Accelerate

GO analysis//SA--gal activity assay

Interestingly, analysis of the genes upregulated by SOX5/6/21 instead resulted in a significant enrichment of GO-terms associated with general tumor suppressor responses, including Apoptotic process , Cellular response to stress Direct p53 effector and Senescence and Autophagy.Furthermore, forced expression of SOX5/6/2...

--

Human

HL

delay aging

28,687,615

Gene

0

1

0

1

0

SOX6

55553

protein coding

GBM

Brain

Glioblastoma

Accelerate

GO analysis//SA--gal activity assay

Interestingly, analysis of the genes upregulated by SOX5/6/21 instead resulted in a significant enrichment of GO-terms associated with general tumor suppressor responses, including Apoptotic process , Cellular response to stress Direct p53 effector and Senescence and Autophagy.Furthermore, forced expression of SOX5/6/2...

--

Human

HL

delay aging

28,687,615

Gene

0

1

0

1

0

SOX21

11166

protein coding

GBM

Brain

Glioblastoma

Accelerate

GO analysis//SA--gal activity assay

Interestingly, analysis of the genes upregulated by SOX5/6/21 instead resulted in a significant enrichment of GO-terms associated with general tumor suppressor responses, including Apoptotic process , Cellular response to stress Direct p53 effector and Senescence and Autophagy.Furthermore, forced expression of SOX5/6/2...

p53

Upregulation

Western blot

Notably, despite a robust increase in p53 protein levels upon forced SOX21 expression, a corresponding upregulation of TP53 gene expression could not be detected.

--

Human

HL

delay aging

28,687,615

Gene

0

1

0

1

0

TP53

7157

protein coding

PA-1(ATCC)

--

Aging

Prevent

Cell morphological analysis//SA--gal activity assay//Western blot

We found that an increase in p16INKA4A expression was detected from days 4 5 post-treatment in TP53-silenced cells, corresponding with the partial release from G2 arrest and increase in (aberrant) mitoses.In control cells, ETO treatment evoked a modest but measurable increase in cell size (hypertrophy) and weak sa-¦Â-g...

OCT4A//p21

--//--

Western blot

Transfection of PA-1 cells with TP53-siRNA successfully silenced TP53 expression throughout the time-course and, as expected, inhibited the increase in P21CIP1 in response to ETO treatment. However, unexpectedly, silencing of TP53 also largely inhibited the upregulation of OCT4A. To confirm this surprising finding, we ...

--

Human

L

delay aging

23,287,532

Gene

0

1

0

1

0

1

0

AGT

183

protein coding

VSMC

Aorta

Atherosclerosis

Accelerate

SA--gal activity assay

SA ¦Â-gal activity was significantly increased in Ang II¨Ctreated VSMCs compared with control cells.Consistent with our in vitro data, treatment with Ang II enhanced SA ¦Â-gal activity in the aortas of apoE-deficient mice.

--

p53-p21

Upregulation

Western blot

Moreover, expression of p21 and p53 was elevated in Ang II¨Ctreated VSMCs.

Human

L

delay aging

16,908,765

Gene

0

1

0

BAG3

9531

protein coding

A172

--

Glioblastoma

Prevent

Cell morphological analysis//Cell viability assay//Colony formation assay//Flow cytometry//Knockdown//SA--gal activity assay

Of note, cells treated with BIS-specific siRNA (SiBIS) showed typical senescence-related phenotypic changes in a time-dependent manner: large, flattened morphology and gradually increased senescence-associated ¦Â-galactosidase (SA-¦Â-Gal) staining: 86.8% of cells were positive for SA-¦Â-Gal staining at 5 days after tra...

p27

--

Western blot//Knockdown

The p27 levels were also progressively accumulated as increasing concentration of SiBIS.

STAT3-SKP2-p27

--

Western blot//Knockdown

Immunoblottig showed that SKP2 levels were prominently decreased as BIS decreased, to 42% of control cells at day 5, which was inversely correlated with p27.We found that the phosphorylation of STAT3, representing the activated form of STAT3 as a transcriptional regulator, was profoundly decreased by BIS depletion in a...

Human

L

delay aging

25,412,315

Gene

0

1

0

1

0

1

0

1

0

1

0

1

0

CDKN2A

1029

protein coding

HCEC

--

Aging

Accelerate

Immunostaining//qRT-PCR

Morphologically, the cells became flattened at Day 42 and floating at Day 49, suggesting an end replication and an end of cell life 20. During the period from Day 42 to Day 49 after the establishment of contact-inhibition in HCECs, there was continuous nuclear presence of p16INK4a and gradual upregulation of senescence...

Bmi1

--

Knockdown//qRT-PCR

The same results were held up by Day 42 following weekly knockdown of p120-Kaiso, resulting in unique downregulation of p16INK4a transcript but upregulation of Bmi1 transcript .

--

Human

L

delay aging

27,739,458

Gene

0

1

0

1

0

CTNND1

1500

protein coding

HCEC

--

Aging

Prevent

Immunostaining//Knockdown//SA--gal activity assay//qRT-PCR

In contrast,weekly knockdowns of p120-Kaiso siRNAs from Day 7 maintained the normal HCEC hexagonal morphology and density till Day 49 as reported11 and prohibited nuclear translocation of p16INK4a, expression of senescence markers,and increase of senescent cells during the entire experimental period.

p16//Bmi1

--//--

Knockdown//qRT-PCR

The same results were held up by Day 42 following weekly knockdown of p120-Kaiso, resulting in unique downregulation of p16INK4a transcript but upregulation of Bmi1 transcript .

JAK2-STAT3//RhoA-ROCK

--//--

Knockdown//qRT-PCR//Western blot

In contrast, 5 weekly knockdown of p120-Kaiso since Day 7 dramatically activated not only RhoA as reported11 but also promoted a sustained transcript expression of JAK2 and STAT3.

Human

L

delay aging

27,739,458

Gene

0

1

0

1

0

1

0

1

0

ZBTB33

10009

protein coding

HCEC

--

Aging

Prevent

Immunostaining//Knockdown//SA--gal activity assay//qRT-PCR

In contrast,weekly knockdowns of p120-Kaiso siRNAs from Day 7 maintained the normal HCEC hexagonal morphology and density till Day 49 as reported11 and prohibited nuclear translocation of p16INK4a, expression of senescence markers,and increase of senescent cells during the entire experimental period.

p16//Bmi1

--//--

Knockdown//qRT-PCR

The same results were held up by Day 42 following weekly knockdown of p120-Kaiso, resulting in unique downregulation of p16INK4a transcript but upregulation of Bmi1 transcript .

JAK2-STAT3//RhoA-ROCK

--//--

Knockdown//qRT-PCR//Western blot

In contrast, 5 weekly knockdown of p120-Kaiso since Day 7 dramatically activated not only RhoA as reported11 but also promoted a sustained transcript expression of JAK2 and STAT3 .

Human

L

delay aging

27,739,458

Gene

0

1

0

1

0

1

0

1

0

PRMT6

55170

protein coding

MCF-7,MDA-MB-231

--

Breast cancer

Prevent

Cell counting//Cell morphological analysis//Knockdown//SA--gal activity assay

PRMT6 KD in both cell lines inhibits growth and specifically leads to a reduction of cells in S phase.Both sh-1 and sh-2 cells show a clear change in morphology, with cells looking bigger and flatter as compared with the scrambled control shRNA (sh-c) . As the morphology and the cell cycle arrest was reminiscent of cel...

p21

Downregulation

qRT-PCR//Western blot//CHIP

Although p16 levels did not change in either MCF7 [the p16 locus is deleted in these cells (24)] or MDA-MB-231 (wt p16), we observed a striking upregulation of p21 messenger RNA (mRNA) and protein levels. In MCF7 cells, the p21 promoter is bound by PRMT6, methylated on H3R2me2a and H3K27me3, and p21 is expressed at low...

--

Human

HL

delay aging

22,987,071

Gene

0

1

0

1

0

1

0

1

0

MYBL2

4605

protein coding

HAEC

--

Aging

Prevent

Cell morphological analysis//SA--gal activity assay

Importantly, the downregulated B-myb cells showed morphological change including a large-flat shape binucleation and polyploidy after 7 days. B-myb-silenced cells also displayed an increase in the proportion of SA-¦Â-gal-positive cells compared with the control.

--

ROS-p53-p21

--

Western blot//SA-¦Â-gal activity assay//Immunostaining

Interestingly, the protein levels of p53 and p21 were significantly increased in B-myb-silenced cells compared with that of the controls.The upregulation of p- p53, p53 and p21 in B- myb knockdown cells could be abolished in the presence of PFT¦Á. PFT¦Á could also obviously attenuate the upregulation of SA- ¦Â- gal act...

Human

L

delay aging

27,878,894

Gene

0

1

0

1

0

KLF6

1316

protein coding

NIH-3T3

--

Aging

Accelerate

SA--gal activity assay

The quantification of SA-¦Â-Gal positive cells showed that the ectopic expression of KLF6 was able to increase the cellular senescence index.

--

Human

L

delay aging

31,824,948

Gene

0

1

0

SENP1

29843

protein coding

HFF

Skin

Aging

Prevent

BrdU assay//Cell morphological analysis//Flow cytometry//SA--gal activity assay

In addition, shSenp1 caused substantial inhibition of cell proliferation.Cell cycle analysis showed that the fraction of HFFs in the G1 phase of the cell cycle increased from 53% in mock-infected controls to 76% in cells 5 days after infection with Senp1 shRNA.Cells infected with Senp1 shRNAs also exhibited an enlarged...

--

p53

--

qRT-PCR

Although there was no significant change in levels of p53 mRNA, repression of Senp1 resulted in enhanced transcriptional activity of p53.

Human

L

delay aging

18,616,636

Gene

0

1

0

1

0

1

0

1

0

CDK2

1017

protein coding

BJ

--

Aging

Prevent

Immunostaining//SA--gal activity assay//Western blot

Indeed, in both human BJ fibroblasts and in MEFs, constitutive ectopic expression of CDK2 abrogated senescence in response to either DNA damage (irradiation), or oncogenic stress (HRasV12 transduction), as evidenced by continued proliferation by day 14 and absence of SABG staining,along with reduction in other protein ...

p53//Rb

--//--

Western blot//qPCR

The lack of repression of CDK2 in p53-null cells and tissues suggested that CDK2 down-regulation is a downstream consequence of p53 activation.As expected, genetic ablation of Rb resulted in increased baseline protein levels of Cdk2.

--

Human

L

delay aging

25,149,358

Gene

0

1

0

1

0

1

0

HMGA1

3159

protein coding

IMR-90

--

Aging

Accelerate

Cell morphological analysis//SA--gal activity assay//SAHF//Western blot

Cells expressing high levels of either HMGA protein underwent an acute cell cycle arrest and displayed features of senescence, including increases in p16INK4a and p53, a senescent morphology, and elevated SA-¦Â-galactosidase activity.These cells also acquired SAHF-like foci that contained HMGA and me-K9H3.

p16

--

Western blot

HMGA1-induced arrest and SAHF formation were clearly impaired in cells expressing sh-p16, despite having similar levels of transgene expression.

--

Human

HL

delay aging

16,901,784

Gene

0

1

0

1

0

1

0

1

0

TERT

7015

protein coding

mTert?/?Fibroblast

--

Aging

Prevent

Western blot

In mTert-/- cells, the levels of the senescence biomarkers p53 and p21 were increased sharply at the M stage, in response to critically shortened telomeres at the same stage. However, unlike mTert -/- cells, the activation of the p53/p21 pathway in mTert+/+ cells immediately triggered the DDR response and up-regulated ...

--

Human

HL

delay aging

31,481,614

Gene

0

1

0

PROM1

8842

protein coding

CD1331 RPC

--

Acute kidney injury

Prevent

SA--gal activity assay

The number of ¦Â-galactosidase expressing cells undergoing senescence appeared significantly higher in the CD133-Kd cells compared to their CD1331 control.The evaluation of T/S ratio revealed a significant reduction in telomere length in CD133-Kd cells compared to their CD1331controls,suggesting an implication of CD133...

--

Wnt-¦Â-catenin

Activation

qRT-PCR//Western blot//Luciferase reporter assay

Interestingly, CD133-Kd cell lines showed a reduced expression of Wnt4 after cisplatin-induced damage in respect to GFP cells. In addition, CD133-Kd cells showed an impaired response to the pharmacological activation of Wnt signaling pathway using CHIR99021 [31].Luciferase activity in CD1331 RPCs was significantly high...

Human

HL

delay aging

29,431,914

Gene

0

1

0

STAG2

10735

protein coding

BJ-2

--

Cancer

Accelerate

Immunostaining//SA--gal activity assay

We observed a significant decrease in the levels of H2AX/p53BP1 DNA damage foci in SA2-depleted late PD cells.We observed a significant decrease in ¦Â-gal positive cells in SA2-depleted late PD cells.

--

Human

L

delay aging

28,819,029

Gene

0

1

0

1

0

CHEK1

1111

protein coding

Fibroblast

Foreskin

Aging

Accelerate

BrdU assay//Cell counting

Numbers of Chk1 siRNA- and FANCD2 siRNA-transfected cells decreased equally until day 3 after irradiation.Forty-eight hours after siRNA transfection, fibroblasts were incubated with BrdU for 24 h. Four per cent of the control siRNA-treated fraction stained positive for the nucleotide analogue. Chk1 depletion induced Br...

--

Human

L

delay aging

21,995,812

Gene

0

1

0

1

0

FANCD2

2177

protein coding

Fibroblast

Foreskin

Aging

Accelerate

BrdU assay//Cell counting//Knockdown

Numbers of Chk1 siRNA- and FANCD2 siRNA-transfected cells decreased equally until day 3 after irradiation.Forty-eight hours after siRNA transfection, fibroblasts were incubated with BrdU for 24 h. Four percent of the control siRNA-treated fraction stained positive for the nucleotide analogue.Remarkably, only 9% of the ...

--

Human

L

delay aging

21,995,812

Gene

0

1

0

1

0

1

0

FBXO5

26271

protein coding

RPE

--

Aging

Prevent

BrdU assay//Cell morphological analysis//Knockdown//SA--gal activity assay

Cells lacking Emi1 were large and flattened and contained relatively large nuclei, a cellular morphology remi- niscent of cellular senescence.Approximately 37 to 65% of RPE cells stained positive for SA-¦Â-gal at 4 or 5 days after Emi1 siRNA treatment, a phenotype that was recapitulated using two additional siRNA targe...

APC/C//E2F//Cyclin E1//ATM

--//--//--//--

Knockdown//Cell morphological analysis//SA-¦Â-gal activity assay//Western blot

Importantly, senescence induction upon Emi1 depletion required APC/C activity, as it was rescued upon codepletion of Cdh1, and was also observed in HCT116 and HeLa cells.Taken together, Emi1 knockdown results in APC/C activation and a consequent decrease in E2F target protein expression with the exception of an increas...

--

Human

HL

delay aging

17,875,940

Gene

0

1

0

1

0

1

0

1

0

RB1

5925

protein coding

MSC

--

Aging

Prevent

Alizarin red S staining//MTT assay//SA--gal activity assay//Western blot//qRT-PCR

Overexpression of RB in late-passage MSCs increased the proliferation rate and differentiation potentials; decreased the expression of senescence-associated markers such as p21, p16, and APO-1; and reduced ¦Â-gal staining.

DNMT//c-JUN

Upregulation//Binding

Western blot

As expected, overexpression of RB in late-passage MSCs increased the protein levels of DNMT1.We found that c-JUN knockdown reduced DNMT1 expression in early- passage MSCs, but not late-passage MSCs, although the expression of RB in early-passage MSCs was not suppressed.

--

Human

L

delay aging

25,455,074

Gene

1

0

1

0

1

0

1

0

1

0

CIP2A

57650

protein coding

AGS

--

Gastric cancer

Prevent

Knockdown//SA--gal activity assay

In control AGS cells, less than 5% of them were ¦Â-Gal-positive, whereas up to 30% of CIP2A siRNA-treated cells were stained with ¦Â-Gal.

--

Human

L

delay aging

18,559,589

Gene

0

1

0

1

0

IL1B

3553

protein coding

HUVEC

--

Aging

Accelerate

SA--gal activity assay//Western blot

To address this, primary HUVECs were treated with recombinant human IL-1¦Â for 6 days, the cell senescence was confirmed by SA-¦Â-galactosidase activity.Furthermore, protein expression levels of senescence markers, such as p53 and p21, were also significantly upregulated in a time dependent way after IL-1¦Â treatment w...

Caspase-1//NLRP3

--//--

Western blot

Interestingly, in the presence of z-YVAD-fmk, a caspase-1 inhibitor, mature IL-1 processing was abolished in senescent HUVECs but pro-IL-1 expression remained unchanged .SiNLRP3 or siASC transfection in the cells could significantly decrease their protein expression induced by bleomycin. As expected, IL-1 productions w...

--

Human

L

delay aging

28,064,010

Gene

0

1

0

1

0

SATB1

6304

protein coding

MEF

--

Breast cancer

Accelerate

Cell morphological analysis//Flow cytometry//SA--gal activity assay

MEFs expressing SATB1 grew markedly slower than controls,stained positive for ¦Â-galactosidase activity and had a flat morphology,indicating a large fraction of SATB1-expressing cells displayed signs of senescence.Consistent with this, we observed a large G1/G0 and a diminished S/G2 population.

p16

Upregulation

SA-¦Â-gal activity assay//Western blot//Flow cytometry

In contrast to wild-type MEFs, SATB1 expression did not cause growth inhibition in p16-/-MEFs. Proliferation was comparable between SATB1- and control virus-infected p16-/- MEFs, and no change in senescence markers or cell cycle distribution was observed.

Rb-E2F1

--

SA-¦Â-gal activity assay//Co-IP

ATB1-expressing TM MEFs infected with RB virus had a markedly higher fraction of senescent cells compared with TM MEFs without SATB1. Both RB-HA and E2F1-HA were immunoprecipitated by Flag-tagged SATB1.The reciprocal interactions were also detected with HA-tagged E2F1 and RB, showing that SATB1 can interact with RB/E2F...

Human

L

delay aging

23,686,316

Gene

0

1

0

1

0

1

0

PAK4

10298

protein coding

MEF

--

Aging

Accelerate

Cell morphological analysis//SA--gal activity assay

We found that Pak4-infected cells stained positive for SA-¦Â-Gal activity.Interestingly, Pak4-expressing cells showed a large and flat shape.

p16//p19ARF//Raf

Upregulation//Upregulation//Activation

SA-¦Â-gal activity assay//Western blot

As expected, the control wild-type MEFs were readily arrested after infection with activated Pak4 or RasV12.However,when Pak4 was expressed in primary p19ARF/p16INK4a null MEFs ,the cells continued to grow and did not senesce.In addition£¬activated Pak4 led to a significant increase in p16INK4a and p19ARFlevels.Further...

ERK-MAPK

Activation

Western blot//BrdU assay//SA-¦Â-gal activity assay

We found that ERK activity was strongly stimulated in primary cells stably expressing Pak4 .?Furthermore, treating cells with a chemical inhibitor of the MEK-ERK pathway partially abrogated Pak4-induced premature arrest in primary fibroblasts and led to a decrease of about 50% in the number of SA-¦Â-Gal-positive cells...

Human

L

delay aging

16,227,603

Gene

0

1

0

1

0

CDC73

79577

protein coding

293T,A549,HUVEC

--

Cancer

Prevent

EdU assay//Knockdown//SA--gal activity assay

Higher percentage of positive SA-¦Â-Gal staining cells was observed in all the three CDC73-KD cells. Moreover, reduced EdU incorporation and cell proliferation were detected upon depletion of CDC73 , indicating decreased expression of CDC73 can reduce DNA synthesis, which is also a well-known molecular phenotype of sen...

--

p53-p21

--

Western blot//Knockdown

However, both mRNA and protein levels of p53 and p21 were remarkably increased after CDC73 knockdown in 293T cells.Similarly, the protein level of p21 was significantly increased in CDC73-deficient HUVECs and A549 cells . These results support the notion that reduced CDC73 expression may induce senescence through the p...

Human

HL

delay aging

29,621,547

Gene

0

1

0

1

0

1

0

PRODH

5625

protein coding

U2OS

--

Aging

Accelerate

EdU assay//SA--gal activity assay

In accordance with our previous results, ectopic expression of PRODH modestly induced senescence in U2OS cells, as judged using SA-¦Â-Gal and EdU assays.Furthermore, the substrate proline added to the medium enhanced the SA-¦Â-Gal activation induced by PRODH overexpression in a dose-dependent manner, which suggests tha...

--

Human

L

delay aging

28,264,926

Gene

0

1

0

1

0

tax

1491938

protein coding

HeLa

--

Aging

Accelerate

Western blot

We use the degradation of I-kBa as an indicator of NF-kB activation and the decrease in cyclin B1 and Skp2 levels with concomitant increase in the levels of p21 and p27 as surrogate markers for senescence induction.Wild-type Tax (WT) and those Tax mutants (V89A and M47) that are potent activators of NF-kB greatly reduc...

RelA//HBZ

--//--

Western blot//Knockdown//Luciferase reporter assay

Most interestingly, knockdown of RelA and to a rather limited extent, that of RelB, but not that of c-Rel or p100 prevented Tax-induced senescence.This is evidenced by the proliferation of EGFP+ HeLa-G/RelAKD cells and the absence of p21 and p27 up-regulation therein after Ad-Tax transduction.Like native HBZ, Flag-HBZ ...

NF-¦ÊB

Activation

Western blot

Tax mutants that are impaired in NF-kB activation , in comparison, had only moderate or no effect on cyclin B, Skp2, p21, or p27.

Human

L

delay aging

21,552,325

Gene

0

1

0

SKP2

6502

protein coding

MEF

--

Prostate cancer

Prevent

SA--gal activity assay

We also found that the ability of Ras to induce cellular senescence was far greater in Skp2-/- MEFs than in wild-type MEFs.

p27//p21//ATF4

--//--//--

Western blot

Although p53 and p19Arf levels remained unchanged, we found that Skp2 deficiency cooperated with Pten inactivation or Arf loss to induce p27 expression. p21 expression was also increased in Pten+/- Skp2-/- and Arf-/- Skp2-/- MEFs.In contrast, Atf4 was markedly induced in Pten+/- Skp2-/- MEFs. Likewise, we also obse...

--

Human

L

delay aging

20,237,562

Gene

0

1

0

KCNJ12

3768

protein coding

PC-3,DU 145,LNCaP,MKN74,SNU638,SNU668,MCF-7,SK-BR-3,T47D

--

Cancer

Prevent

Cell morphological analysis//Knockdown//SA--gal activity assay//Western blot

Doxorubicin-treated PC-3 cells overexpressing Kir2.2 exhibited improved survival, decreased growth inhibition, and reduced accumulation of SA-¦Â-Gal compared with doxorubicin-treated control PC-3 cells.All tested cancer cells from different tumor tissues, including prostate (PC-3, DU145, and LNCaP), stomach (MKN74, SNU...

p27

--

Knockdown//Immunostaining//Western blot

Kir2.2 knockdown induced ROS accumulation. Rescue of Kir2.2 levels by Kir2.2 overexpression restored intracellular ROS to levels comparable with those in controls, indicating that the accumulation of ROS was directly de pendent on the level of Kir2.2.p27 knockdown decreased ROS generation and the ROS scavenger NAC prev...

--

Human

L

delay aging

20,841,375

Gene

0

1

0

1

0

1

0

1

0

HRAS

3265

protein coding

MEF

--

Aging

Accelerate

Cell morphological analysis

In the case of overexpressed oncogenic HRas, cells were analyzed 6 days post-infection when, as expected, cells had a clear senescent morphology.

--

Human

L

delay aging

19,421,407

Gene

0

1

0

CDKN2A

1029

protein coding

2BS

--

Aging

Accelerate

Cell morphological analysis//Flow cytometry//SA--gal activity assay

The 2BS/p16 cells showed increasing gross en- largement, flattening, and accumulation of granular cytoplas- mic inclusions.Only sporadic SA-¦Â-gal-positive cells were seen in 2BS/ASp16 (A5, PD45) and young (PD29) cells, whereas almost all of 2BS/p16 (P3, PD43) cells were strongly stained, as were the senescent 2BS cont...

--

p16-CDK4-pRb

--

Western blot

p16INK4acan inhibit the activity of CDKs,thereby blocking the entry of the proliferating cells to S phase through the p16INK4a/CDK4/cyclin D/pRB pathway. The function of p16INK4a is to maintain pRB in its hypophosphorylated Activate state.pRB phosphorylation status in 2BS/ASp16 (A10, PD50) cells (lane 1) is similar to ...

Human

L

delay aging

11,606,567

Gene

0

1

0

1

0

1

0

SOX10

6663

protein coding

0002-ARM,UACC 1022,0380-MMU

--

Melanoma

Prevent

Cell counting//Cell morphological analysis//SA--gal activity assay//SAHF

Significant increases in SA-¦Â-Gal activity were seen in all 3 lines when stably transduced with shSOX10 hairpins, suggesting that loss of SOX10 induces senescence in melanoma cells. Another hallmark of cellular senescence, senescence-associated heterochromatin foci (SAHF), was observed upon chromatin binding protein H...

E2F1//Rb//MITF//p16//p27//p21

--//--//--//--//--//--

Western blot

In all three melanoma lines, SOX10 knockdown led to reduced levels of E2F1 protein and total RB protein.Reduced MITF protein was observed upon shSOX10 knockdown in both 0380-MMU and 0002-ARM cells.We observed moderate p16 expression in 0380-MMU cells;however,p16 levels remained unchanged following SOX10 knockdown. Weco...

--

Human

HL

delay aging

23,913,827

Gene

0

1

0

1

0

1

0

1

0

E2

1489080

protein coding

HeLa

--

Aging

Accelerate

SA--gal activity assay

After infection with the E2 virus, virtually all HeLa/LXSN cells displayed intense blue staining indicative of SA-¦Â-gal activity and cellular senescence.The E2-infected HeLa/16E7 cultures contained cells displaying a flattened morphology and SA¦Â-gal activity interspersed with numerous proliferating colonies.

E7

--

SA-¦Â-gal activity assay//Cell morphological analysis

In contrast, as reported previously, the E2-infected HeLa/16E7 cultures contained cells displaying a flattened morphology and SA-¦Â-gal activity interspersed with numerous proliferating colonies that did not stain, demonstrating partial protection from senescence by the wild-type HPV16 E7 protein.

Rb

Activation

Western blot

The E2 protein repressed expression of cyclin A in HeLa/LXSN cells, indicating that the Rb pathway was activated.

Human

L

delay aging

15,126,344

Gene

0

1

0

SOX5

6660

protein coding

Glial cell

--

Glioma

Accelerate

Cell morphological analysis//SA--gal activity assay

We performed SA-¦Â-gal staining of these cells and found that there were an increased number of SA-¦Â-gal-positive cells in Ink4a-/- cells infected with Sox5+PDGFB or Sox5 alone.In Arf-/- cells, there was an increased number of SA-¦Â-gal-stained cells in Sox5-infected cells only.

p27//Akt

Upregulation//Downregulation

Western blot

When analyzing p27Kip1protein levels, we found that p27Kip1was clearly upregulated in the Sox5-infected Ink4a-/- cells compared with control and PDGFB-infected cells and that it remained high in the Sox5+PDGFB-infected cells.The total and activated levels of Akt were decreased specifically in the Sox5-stimulated Ink4a-...

PDGFB

--

Immunostaining

To study the proliferation status of Sox5 + PDGFB infected Ink4a-/- and Arf-/- cells, expression of Ki67, a marker of cell proliferation, was analyzed with triple immunofluorescence stainings . In Ink4a-/- cells, HA(PDGFB expression) and V5 (Sox5 expression) double-positive cells were completely negative for Ki-67, whe...

Human

HL

delay aging

19,219,070

Gene

0

1

0

1

0

G6PD

2539

protein coding

HFF

--

Aging

Prevent

Cell morphological analysis//SA--gal activity assay

There was an increase in the percentage of SA-¦Â-Gal positive HFF1 cells, from less than 8% at PDL 22 to about 50% at PDL 52, and to over 95% at PDL 60. The majority of HFF3 cells remained SA-¦Â-Gal negative at PDL 52, and a few cells (less than 5%) were stained positive at PDL 60.Some HFF1 cells showed the senescent m...

--

Human

L

delay aging

10,980,404

Gene

0

1

0

1

0

WIF1

11197

protein coding

LN-229,LN319

--

Glioblastoma

Accelerate

Cell morphological analysis//Flow cytometry//Immunostaining//SA--gal activity assay

We detected an increased percentage of senescence-like cells in WIF1-transfected clones with a positive relationship to WIF1 secretion of the respective clones. Similar differences were observed upon double staining of the cells with SA-¦Â-galactosidase and DAPI, which visualizes nuclear morphology. In the LN319- and L...

--

Wnt

Downregulation

Luciferase reporter assay

Indeed, forced expression of WIF1 inhibited Wnt activity in a dose-dependent manner.

Human

HL

delay aging

21,642,372

Gene

0

1

0

1

0

1

0

1

0

CXCL8

3576

protein coding

HUVEC

--

Aging

Prevent

Flow cytometry//PI staining//SA--gal activity assay

However, IL-8 dose-dependently inhibited the increase of SA-beta-gal-positive cells when co-incubated with HUVECs.These results suggested that 150 ¦ÌM H2O2 inhibited cell cycle progression at G1 phase, however IL-8 prevented this effect.

hTERT

Upregulation

qRT-PCR

QRT-PCR analysis showed that H2O2 down-regulated the expression of hTERT mRNA and the effect was suppressed by IL-8 in a dose- dependent manner.

NF-¦ÊB//p38 MAPK

Downregulation//Downregulation

Western blot

H2O2 was found to activate NF-¦ÊB and p38(MAPK) pathway in a time-dependent manner, but the effect was suppressed by pretreatment of IL-8.

Human

L

delay aging

23,597,430

Gene

0

1

0

1

0

1

0

NAT10

55226

protein coding

HGPS

--

Hutchinson-Gilford progeria syndrome

Accelerate

SA--gal activity assay

Similarly, although NAT10 depletion strongly decreased the proportion of HGPS cells positive for senescenceassociated -galactosidase, this was not the case when NUP153 or TNPO1 was codepleted with NAT10.

--

TNPO1

--

Knockdown//Microarray//Western blot

We observed that 70% of the genes showing significantly increased or decreased expression upon NAT10 depletion alone in control fibroblasts were not modified anymore upon simultaneous depletion of TNPO1, despite similar NAT10 protein knockdown.

Human

HL

delay aging

29,970,603

Gene

0

1

0

NUTF2

10204

protein coding

HGPS(HGPS 11513),Fibroblast

--

Hutchinson-Gilford progeria syndrome

Prevent

Knockdown//SA--gal activity assay

In addition to the effect on chromatin, disrupting nuclear Ran by depleting NTF2 also promoted the entry of control fibroblasts into senescence as measured by senescence-associated -galactosidase staining.

--

Human

HL

delay aging

29,970,603

Gene

0

1

0

1

0

OPA1

4976

protein coding

--

Liver,Skin,Colon

Aging

Prevent

SA--gal activity assay//Western blot

To further support the aging phenotype, we checked several markers of aging like ¦Â-galactosidase and p21. Both are significantly increased in liver, skin, and gut.

--

Human

L

delay aging

28,552,492

Gene

0

1

0

1

0

E2

1489080

protein coding

HeLa/LXSN-1

--

Cervical cancer

Accelerate

SA--gal activity assay

After E2 expression, HeLa/LXSN-1 cells displayed a flattened morphology and intense blue staining indicative of SA-Gal activity and senescence.

--

p53

Upregulation

SA-¦Â-gal activity assay//Western blot

Strikingly, the E2 protein did not induce the HeLa/16E7-p53CTF cells to display blue staining or senescent morphology;rather, the cells formed colonies that did not stain for SA-Gal activity.Full-length, wild-type p53 was expressed in all of the cell lines, and as expected, its expression was markedly induced by E2-med...

Human

L

delay aging

15,047,823

Gene

0

1

0

SATB1

6304

protein coding

--

Brain

Parkinson's disease

Prevent

Knockdown//SA--gal activity assay//Western blot

Given this, we sought to investigate whether SATB1KO DA neurons present the classical features of cellular senescence. First we observed a dramatic increase in acidic lysosomal (SA-¦Â-gal) activity, the hallmark senescence biomarker.We found upregulation of the majority of SASP factors at 50 days of differentiation in ...

p21

Downregulation

Western blot//CHIP//Knockdown//Luciferase reporter assay

Both CDKN1A transcription and p21 protein levels were significantly increased in SATB1KO DA neurons.Using ChIP-seq in DA neurons, we found that SATB1 binds the regulatory region of CDKN1A.To determine whether SATB1 directly represses CDKN1A, we performed a luciferase reporter assay and found that, under conditions of S...

--

Human

HL

delay aging

31,543,366

Gene

0

1

0

1

0

1

0

SHH

6469

protein coding

Human endometrial stem cell

--

Recurrent pregnancy loss

Prevent

SA--gal activity assay//Western blot

Importantly, SHH significantly attenuated replicative senescenceinduced SA-¦Â-Gal activity.The oxidative stress-induced expression of these senes- cence-associated (L-6, p16,p18, and p21) was significantly attenuated by SHH treatment. We conducted the additional set of experiments to further confirm the alleviating eff...

SERPINB2

Downregulation

Western blot//qRT-PCR

Consistent with our hypothesis, replicative and oxidative stress-induced senescence significantly enhanced SERPINB2 expression at both the mRNA and protein levels.SHH treatment markedly suppressed SERPINB2 expression in endometrial stem cells. Importantly, senescence-induced SERPINB2 expression was significantly attenu...

--

Human

HL

delay aging

31,080,015

Gene

0

1

0

1

0

SPRY1

10252

protein coding

ASC

--

Aging

Prevent

BrdU assay//ELISA//Growth curve assay//Knockdown//SA--gal activity assay//Western blot

SPRY1 KO ASCs showed a proliferation arrest,CRISPR-GFP expressing cells served as negative control. Moreover, the anti-proliferative effect observed in SPRY1 KO ASCs was associated with significantly increased numbers of senescence-associated (SA) ¦Â-Galactosidase (¦Â-Gal) positive ASCs and decreased Ki67 abundancy.CCL...

p53//p21//Rb

--//--//--

Western blot

SPRY1 KO ASCs showed a considerable upregulation of p53 and its target p21Cip1 associated with Rb activation (hypo-phosphorylation).

Ras-MAPK//NF-¦ÊB

--//--

Knockdown//Western blot

Sprouty1 protein was depleted by both shRNA #1 and shRNA #2 and silencing of Sprouty1 elevated the abundance of phosphorylated ERK1/2 in PM4-stimulated ASCs compared to shCtrl indicating augmented MAPK activation.C/EBP¦Â protein was significantly elevated in SPRY1 KO ASCs and nuclear translocation of the NF-¦ÊB subunit...

Human

HL

delay aging

32,304,210

Gene

0

1

0

1

0

1

0

1

0

1

0

1

0

SRSF3

6428

protein coding

293T,HUVEC,MEF,NIH-3T3

--

Aging

Prevent

CCK-8 assay//Flow cytometry//Knockdown//SA--gal activity assay//qRT-PCR

RNA interferences using two shRNAs targeting SRSF3 caused increased senescenceassociated ¦Â-galactosidase (SA-¦Â-gal) staining in both human (293T and HUVEC) and mouse (MEF and NIH3T3) cells. In addition, SRSF3-KD reduced cell growth rate in tested cell lines.Notably, SRSF3-KD caused a common decrease of S phase percen...

PTEN

--

Luciferase reporter assay//Western blot

As knockdown of SRSF3 induced 3¡ä UTR shortening of PTEN and transcripts with shortened 3¡ä UTR of PTEN generated more protein than those with the longer one, one would expect that SRSF3-KD can increase the protein level of PTEN.Consistently, SRSF3 knockdown with two shRNAs both led to higher PTEN protein abundance in ...

PI3K-Akt

--

Knockdown//Western blot

Furthermore, SRSF3 knockdown attenuated the abundance of p-AKT but not that of the total AKT,coinciding with the result of PTEN upregulation.

Human

HL

delay aging

30,835,716

Gene

0

1

0

1

0

1

0

1

0

1

0

ITGB4

3691

protein coding

Mice airway epithelial cell

Mice airway epithelia

Asthma

Prevent

Immunostaining//Knockdown//SA--gal activity assay

Our results showed that ITGB4 deficient airway epithelial cells presented typical premature senescence. The rate of positive SA-¦Â-gal staining in airway epithelial cells of ITGB4-/- mice was significantly higher than that in control mice.The cellular proliferative capacity of the airway epithelial cells in ITGB4-/- mi...

--

p53-p21

--

Knockdown//qRT-PCR//Western blot

Also, we have previously found increased expression of p53 and p21 in airway epithelia of ITGB4-/- mice. Therefore, we further detect the activation of p53/p21 signaling pathway by qPCR and western blotting in HBE cells. We found that p-p53 (the activated form of p53), p53 and p21 were significantly upregulated in ITGB...

Human

L

delay aging

30,636,108

Gene

0

1

0

1

0

1

0

TRPC7

57113

protein coding

--

Skin

Aging

Accelerate

Knockdown//SA--gal activity assay//Western blot

In the absence of UVB, skin phenotype was similar between wild-type and TRPC7+/? or TRPC7?/? mice. In wild-type mice, UVB exposure induced severe desquamation and erythema of the skin. However, in TRPC7+/? and TRPC7?/? mice, UVB exposure induced slight or no damage and less epidermal thickening than in wild-type mice.S...

--

Human

HL

delay aging

31,755,176

Gene

0

1

0

1

0

1

0

TET1

80312

protein coding

H1299,H1975,H226,H441,Calu-6

--

Lung cancer

Prevent

Cell morphological analysis//Colony formation assay//Crystal violet assay//Knockdown//SA--gal activity assay

TET1 knockdown significantly reduced proliferation of H1299, H1975, H226 and H441 cells at 120 h post-transfection by 63%, 40%, 24% and 21%, respectively, as determined using crystal violet assay. Furthermore, TET1 knockdown reduced anchorage independent growth of H1299, H226, and Calu6 lines as evident by 64%, 62% and...

p53//p21

Binding//--

CHIP//qRT-PCR

As expected, no enrichment of p53 at its predicted binding site within the TET1 promoter region was detected in H1299 cells characterized by a p53-null mutation. Conversely, 23,800- and 13,500-fold enrichments of p53 at the TET1 promoter were found in the WT p53 cell lines A549 and H2228,respectively. Furthermore, p53 ...

--

Human

HL

delay aging

30,622,117

Gene

0

1

0

1

0

1

0

1

0

1

0

SARS1

6301

protein coding

HeLa 1.2.11,BJ

--

Aging

Accelerate

FISH//Knockdown//SA--gal activity assay

We observed an unexpected increase in SA-¦Â-gal activity and increased levels of cellular senescence signaling molecules, such as P21, P16, and ¦Â-galactosidase (¦Â-Gal)32¨C34 at late cell passages of both cells; these changes were even observed in HeLa 1.2.11 cells, which undergo little replicative senescence, suggest...

POT1

Binding

Pull-down assay//Immunostaining//CHIP//Co-IP

SerRS was partially colocalized with POT1 in the nucleus.The interaction between SerRS and POT1 was further confirmed by their Co-IP from HeLa cells.V5-tagged POT1 was able to be coprecipitated with Flag-tagged SerRS via Flag antibody-mediated isolation; the reverse experiment with a V5 antibody produced a complementar...

--

Human

L

delay aging

31,815,007

Gene

0

1

0

1

0

1

0

TLR4

7099

protein coding

MLEC

--

Emphysema and COPD

Prevent

Flow cytometry//Knockdown//SA--gal activity assay

TLR4?/? mouse lung Ec (MLEC) showed increase in SA©\¦Â©\gal activity, even at low passages, compared to WT MLEC.To further investigate the role of TLR4 in cellular senescence, we examined the cell growth rate and cell cycle analysis between TLR4?/? and WT MLEC. TLR4?/? MLEC had a significantly decreased rate of cell gr...

p16//HDAC2

Downregulation//--

qRT-PCR//Western blot

In contrast, TLR4 overexpression resulted in a significant decrease in both p16INK4a mRNA and protein expression in hLMVEC.We found that HDAC2 mRNA expression significantly decreased in lungs from TLR4?/? mice compared to WT. We also found that phosphorylated (p)and total©\HDAC2 protein expression were significantly de...

--

Human

L

delay aging

30,790,400

Gene

0

1

0

1

0

1

0

MANF

7873

protein coding

--

Adipose

Aging

Prevent

Knockdown//SA--gal activity assay//qRT-PCR

We also found signs of cellular senescence in MANFHet mice, but not WT littermates, at 10 months of age: elevated senescence-associated ¦ÂGal activity in subcutaneous and visceral WAT, increased levels of 4-HNE adducts, and increased expression of p16 and IL-6.

--

Human

HL

delay aging

31,489,403

Gene

0

1

0

1

0

1

0

CD9

928

protein coding

HUVEC

--

Atherosclerosis

Accelerate

BrdU assay//Cell morphological analysis//Flow cytometry//Immunostaining//SA--gal activity assay//Western blot

Young cells transduced with CD9 adenovirus were enlarged and flattened. Moreover, CD9 upregulation increased SA¦ÂG staining, but decreased BrdU incorporation, Ki67 immunoreactivity, the proportion of cells in the S phase, and endothelial tube formation. In addition, the levels of p53, p-p53, and p21 proteins increased.

--

PI3K-Akt-mTOR-p53

Activation

Knockdown//Western blot//SA-¦Â-gal activity assay

Pretreatment with LY294002, a specific inhibitor of PI3K [42], or rapamycin, an inhibitor of mTOR [43], reduced the levels of p53 and p21 and SA¦ÂG staining induced by CD9 overexpression. Knockdown of PIK3CA, but not that of PIK3CB, significantly decreased the levels of pAKT, p53, p-p53, pS6K, and p21 proteins, as well...

Human

HL

delay aging

32,346,137

Gene

0

1

0

1

0

1

0

1

0

1

0

1

0

PRDX6

9588

protein coding

C2C12

Gastrocnemius

Metabolic Sarcopenia

Prevent

Knockdown//SA--gal activity assay//qRT-PCR

We screened the expression of 84 key genes involved in the senescence program on gastrocnemius of wt and Prdx6-/- mice. A significant up-regulation of p53 (p < 0.05),Cdkn1b (p < 0.05) and Cdkn1c (p < 0.05), was found in Prdx6-/- mice.Prdx6-/- mice showed increase in activity of SA-¦Â-Gal compared to wt mice (p < 0.005)...

SIRT1

--

Western blot//Knockdown

Following the nuclear and cytoplasmic proteins fractionation, indeed, we found that in Prdx6-/- mice SIRT1 localized predominantly in the cytoplasm (p < 0.05) rather than in the nucleus (p < 0.0005) compared to wt, suggesting reduced levels of Prdx6 lead to an impairment of SIRT1 nuclearcytoplasmic shuttling.

p53-p21

--

Western blot//Knockdown

As expected, p53 acetylation was significantly increased in Prdx6-/- mice compared to wt mice, confirming the SIRT1 reduced nuclear activity. Acetylated p53 induces p21, a cyclin-dependent kinase inhibitor 1 able to regulate cell cycle and directly blunt telomerase activity . Consistently with the reduction of ATLR and...

Human

HL

delay aging

32,316,601

Gene

0

1

0

1

0

1

0

BMI1

648

protein coding

B-MSC

--

Aging

Prevent

Cell counting//Knockdown//SA--gal activity assay//qRT-PCR

We then serially passaged BMSCs in vitro to examine the proliferative capacity of Bmi1-deficient BMSCs. Whereas wildtype BMSCs expanded significantly over three passages, Bmi1-deficient BMSCs ceased proliferation upon passage 2 and failed to expand in later passages.Bmi1-deficient BMSC cultures exhibited significantly ...

--

Human

HL

delay aging

31,257,132

Gene

0

1

0

1

0

1

0

1

0

SIRT2

22933

protein coding

NP

--

Disc degenerative disease

Prevent

Flow cytometry//Knockdown//RT-PCR//SA--gal activity assay//Western blot

NP cells expressed significantly higher ¦Â-gal and MMP3/9 levels with higher IL-1b stimulation. NP cells were transfected with Lenti-sirt2 to overexpress Sirt2 protein. Meanwhile, Lenti-NC was used as the sham group. The function of lentivirus transfection was verified through WB analysis. Results indicated that these ...

IL-1¦Â//SOD1//SOD2

Downregulation//Upregulation//Upregulation

RT-PCR//Western blot//Flow cytometry

Results indicated that these cells exhibited significantly less ¦Â-gal, MMP3/9 activity than those in IL-1b-induced group.Sirt2 expression decreased significantly in cells after treatment with IL-1b. Meanwhile, total ROS level decreased obviously under the treatment of Lenti-sirt2.In addition, anti-oxidative SOD1 and ...

p53-p21

Downregulation

Western blot//RT-PCR

Western blot and RT-PCR results indicated that Sirt6 overexpression significantly decreased the expressions of p53 and p21.

Human

L

delay aging

30,981,502

Gene

0

1

0

1

0

1

0

1

0

1

0

LSG1

55341

protein coding

MRC-5

--

Aging

Prevent

BrdU assay//Knockdown//SA--gal activity assay//Western blot

Next, we used siRNA SMARTpools to EFL1 and LSG1 and observed the expected reduction in BrdU incorporation, induction of acidic ¦Â©\galactosidase activity and induction of p16 immunoreactivity.

--

p53

--

Knockdown//BrdU assay//qRT-PCR//DAPI staining

E6£¨E6 abrogated p53 expression£© expression led to maintained BrdU incorporation upon LSG1 knockdown, indicating p53 dependence. Expression of E7£¨E7 expression enhanced p53 levels£©did not rescue the inhibition of cell cycle elicited by LSG1 knockdown. Once again, inhibition of the p53 pathway led to bypass of shLSG1...

Human

HL

delay aging

31,148,378

Gene

0

1

0

1

0

1

0

1

0

SBDS

51119

protein coding

MRC-5

--

Aging

Prevent

BrdU assay//Knockdown//SA--gal activity assay//Western blot

Next, we used siRNA SMARTpools to EFL1 and LSG1 and observed the expected reduction in BrdU incorporation, induction of acidic ¦Â©\galactosidase activity and induction of p16 immunoreactivity.

--

p53

--

Knockdown//BrdU assay//qRT-PCR//DAPI staining

E6£¨E6 abrogated p53 expression£© expression led to maintained BrdU incorporation upon LSG1 knockdown, indicating p53 dependence. Expression of E7£¨E7 expression enhanced p53 levels£©did not rescue the inhibition of cell cycle elicited by LSG1 knockdown. Once again, inhibition of the p53 pathway led to bypass of shLSG1...

Human

HL

delay aging

31,148,378

Gene

0

1

0

1

0

1

0

1

0

LMNB1

4001

protein coding

HBEC

--

Chronic obstructive pulmonary disease

Prevent

ELISA//Immunostaining//Knockdown//SA--gal activity assay//Western blot

Lamin B1 knockdown was sufficient to induce cellular senescence by means of SA-¦Â-gal staining, phospho-histone H2A.X (Ser139) staining of DNA damage, and Western blotting of CDKN2A/p16 and CDKN1A/p21, which was significantly enhanced by CSE treatment in HBEC. To determine SASP status, CXCL8 secretion was examined. Sig...

--

mTOR

Downregulation

Western blot//Knockdown//qRT-PCR

In comparison with non-smoker lungs, electron microscopic evaluations showed a significant increase in mitochondrial counts in airway epithelial cells in COPD lungs . In comparison with nonsmokers and non-COPD smokers, lamin B1 and DEPTOR mRNA were significantly reduced in HBEC of COPD patients. Consistent with CS-expo...

Human

L

delay aging

30,692,212

Gene

0

1

0

1

0

1

0

1

0

1

0

STUB1

10273

protein coding

HEK293T

--

Aging

Prevent

SA--gal activity assay//Western blot

The immunoblotting results showed that H2O2 increased the expression of p53 and p21 in HEK293T cells, indicating the occurrence of cell senescence. When HEK293T cells were transfected with STUB1 plasmid and treated with H2O2, cell senescence was significantly reduced, demonstrated by the decrease of SA-¦Â-Gal positive ...

BMAL1

Downregulation

Western blot

The endogenous BMAL1 protein was significantly reduced after expressing Myc-STUB1.Gradient increase of the transfected STUB1 led to a progressive reduction of BMAL1 .

--

Human

L

delay aging

32,041,778

Gene

0

1

0

1

0

BTK

695

protein coding

--

Brain

Aging

Accelerate

Knockdown//SA--gal activity assay//qRT-PCR

To test whether BTK inhibition could prevent the age-dependent buildup of senescent cells in the brain, we measured the expression of different markers of senescence in brains of control and ibrutinib-treated Zmpste24?/? mice.This was concomitant with a decrease in p53 and p16 levels, as expected. In line with this, mR...

--

Human

L

delay aging

31,736,210

Gene

0

1

0

1

0

1

0

CDKN2A

1029

protein coding

AECII

--

Chronic obstructive pulmonary disease

Accelerate

EdU assay//Knockdown//SA--gal activity assay

In vivo cell proliferation was assessed by EdU incorporation. Deleting p16 significantly increased cell proliferation from 3.6% to 5.3%.When exposed to CSE, the percentage of senescent p16+/+ AECIIs increased as assessed by flow ¦Â-gal activity. Deletion of p16 completely prevented the CSE-induced senescence of AECII (...

Cyclin D

--

Western blot

There was a much larger increase in cyclin D in p16?/?compared with p16+/+lungs upon CS exposure, supporting the observation of enhanced cell proliferation and regeneration in p16?/?lung.

IGF-1-Akt1

--

qRT-PCR//Western blot//Knockdown

Deletion of p16 increased IGF1 mRNA and protein. This translated to a 7.83-fold increase in IGF1 protein in p16?/? lung compared with p16+/+.Similarly, total Akt was substantially elevated in p16?/? lungs and increased with CS.

Human

HL

delay aging

31,428,695

Gene

0

1

0

1

0

1

0

ATP6AP2

10159

protein coding

C2C12

--

Sarcopenia

Accelerate

SA--gal activity assay//Western blot

In the differentiated myo-tube from (P)RR©\expressing C2C12 cells, we detected positive SA©\¦Â©\gal staining with an increase in ¦ÃH2AX, a senescent marker, and increased expression of TNF©\¦Á, a senescence©\associated secretory phenotype, indicating that (P)RR expression induced cellular senescence. Moreover, aging ma...

--

Wnt-YAP

Activation

Western blot//Immunostaining

As expected, ABC was significantly increased and nuclear localization of ¦Â©\catenin could be observed in the muscles of (P)RR©\Tg mice, indicating activation of Wnt/¦Â©\catenin signaling by (P)RR .Wnt and YAP activities were enhanced in myotubes from (P)RR©\expressing C2C12 cells. Treatment with verteporfin, a small m...

Human

L

delay aging

31,282,603

Gene

0

1

0

1

0

SIRT1

23411

protein coding

HUVEC

--

Heart failure

Prevent

SA--gal activity assay

The inhibition of Sirt1 activity by EX-527 caused an increase of senescence in RP-ECs compared with baseline (P = 0.001).

Cat//SOD

--//--

Enzyme activity assay

The CRP enhanced Sirt1 activity measured in PBMCs from patients (RP vs P, P= 0.02). Likewise, Cat and SOD activities measured in serum were greater in RP than in P (P < 0.005 and P < 0.05, respectively).

--

Human

L

delay aging

28,331,525

Gene

0

1

0

GDF11

10220

protein coding

HFL-1,Primary bronchial epithelial cell

--

Chronic obstructive pulmonary disease

Prevent

Cell counting//SA--gal activity assay//Western blot

Treatment with GDF11 significantly inhibited the CSE-augmented expression of p16 and p53 and the CSE-augmented SA-¦Â-gal activity in a concentration-dependent manner. CSE significantly delayed cell proliferation, but treatment with GDF11 ameliorated the delay in cell growth. Similar anti-senescent effects of GDF11 were...

--

Smad2/3

--

Western blot

As previously reported in other types of cells,GDF11 phosphorylated Smad2/3,and the phosphorylation was inhibited by an activin receptor-like kinase (ALK)4/5 inhibitor, SB431542, in HFL-1 cells.

Human

L

delay aging

28,455,454

Gene

0

1

0

1

0

1

0

SATB2

23314

protein coding

B-MSC

Bone

Aging

Prevent

Immunofluorescence//SA--gal activity assay

To examine replicative senescence, we repeatedly subcultured T-BMSCs transfected with either Lev-Satb2 or Lev-GFP.We observed that T-BMSCs that overexpressed Satb2 exhibited enhanced anti-aging capacity, as revealed by SA-¦Â-gal staining at the 10th passage.Compared with the Lev-GFP group, the Lev-Satb2 group displayed...

--

Human

HL

delay aging

25,200,657

Gene

0

1

0

1

0

NAMPT

10135

protein coding

SMC

--

Atherosclerosis

Prevent

Knockdown//SA--gal activity assay

In the longer lived HITC6 SMCs,lifespan extension by Nampt was even more striking, with an additional 6.3¡À0.3 population doublings or a 71 ¡À7% extension of lifespan.We quantified the proportion of senescent SMCs in successive subcultures incubated with 10 nM FK866, a concentration we determined reduced Nampt activity...

SIRT1//p53

Activation//Downregulation

Western blot

SMCs overexpressing Nampt had a 86 ¡À 4% (p=0.03, n =4) increase in SIRT1 activity. We were surprised to find that Nampt overexpression also modestly increased abundance of SIRT1 protein (1.3¡À0.3-fold, p =0.02), although not enough to fully account for the increased deacetylase activity.this agerelated increase in p53...

--

Human

L

delay aging

17,307,730

Gene

0

1

0

1

0

SATB2

23314

protein coding

B-MSC

--

Aging

Prevent

Knockdown//SA--gal activity assay

Although cellular proliferation remained largely unaltered, enforced SATB2 overexpression significantly enhanced pluripotency markers expression, whereas reduced cellular senescence as reflected by reduced SA-¦Â-Gal-positive cells and senescence marker expression.The cellular proliferation rate significantly decreased ...

--

Nanog

Upregulation

Knockdown//qRT-PCR//CHIP

Our data reveal that the level of Nanog transcript was induced upon SATB2 overexpression, and reduced following SATB2 knockdown.Significant enrichment of SATB2 was identified in four putative binding sites in Nanog promoter region.

Human

L

delay aging

27,632,702

Gene

0

1

0

1

0

PRDX2

7001

protein coding

Human primary Chondrocyte

--

Osteoarthritis

Prevent

Immunostaining//RT-PCR//SA--gal activity assay//Western blot

Western blot analysis showed that IL-1¦Â-induced chondrocytes expressed a large amount of ¦Â-gal, p53, and p21, while Prx II could attenuate the effect of IL-1¦Â and decrease the expression of ¦Â-gal, p53, and p21. RT-PCR results showed that Prx II increased the expression of anti-aging molecule BMI-1 and decreased the...

--

p16

Downregulation

RT-PCR//Western blot

Western blot results showed that IL-1¦Â-induced chondrocyte expressed more p16 while CDK4, CDK6, and E2F1 decreased, and overexpression of Prx II attenuated the effect of IL-1¦Â. The results of RT-PCR were similar to those of Western blot.

Human

L

delay aging

32,329,817

Gene

0

1

0

1

0

1

0

1

0

MSN

4478

protein coding

HDMEC

--

Aging

Prevent

Cell morphological analysis//Knockdown//RT-PCR//SA--gal activity assay//Western blot

Moesin knock-down HDMECs showed the characteristics of aging, i.e., they were large, flat, and stellate, beginning at the early stage of passage 6. Moesin knock-down HDMECs from the early stage of passage 6 were stained blue with SA-¦Â-gal. HDMECs at late passages higher than passage 25 stained blue in all serial subcu...

--

Human

L

delay aging

20,376,899

Gene

0

1

0

1

0

1

0

1

0

1

0

SGK1

6446

protein coding

HUVEC,SGK1WT

--

Atherosclerosis

Prevent

SA--gal activity assay//Telomerase activity assay

Infected HUVEC lines have been cultured until the last stage of senescence, represented as arrest of cellular proliferation (PDL16). During serial passages of HUVEC, the activity of SA-¦Â-gal in control pLPCX and in SGK1¦¤60 increased by ~5-6-fold from PDL6 to PDL16. SGK1WT was able to significantly reduce SA-¦Â-gal ac...

hTERT

Binding

Co-IP//Pull-down assay//Flow cytometry//Immunostaining

We found that SGK1 co-immunoprecipitates with hTERT in all cellular constructs, proving a protein-protein interaction. However, a different shift was observed between total SGK1¦¤60 and hTERT immunoprecipitate, suggesting that hTERT interacts only with SGK1 full length,and further supporting the previously reported ina...

--

Human

L

delay aging

26,230,157

Gene

0

1

0

1

0

SEMA4C

54910

protein coding

MDA-MB-231

--

Breast cancer

Prevent

Cell counting//Cell morphological analysis//Immunostaining//Knockdown//SA--gal activity assay

Cell counting assays demonstrated that knockdown of SEMA4C significantly inhibited 24 MDA-MB-231 cellular growth ability. Cell immunohistochemistry also indicated that MDA-MB-231 cells expressing shSEMA4C showed a >50% reduction in proliferation rate as assessed by anti-human PCNA staining.However, in the following day...

--

p53-p21

--

Western blot//Knockdown

The ratio of phospho-p21Cip1¨CThr145 to total p21Cip1 increased in the MDA-MB-231 cells transfected with either siSEMA4C or siPLEXINB2,suggesting that knockdown of SEMA4C or PLEXINB2 induced activation of p53, followed by activation of p21Cip1.

Human

HL

delay aging

31,308,149

Gene

0

1

0

1

0

1

0

1

0

1

0

ACKR3

57007

protein coding

C4-2B

--

Prostate cancer

Prevent

Cell morphological analysis//Knockdown//SA--gal activity assay

After one month in culture, no further proliferation could be observed, and all cells had developed a broad, flattened morphology with numerous long protrusions.In proliferation-arrested CRISPR-Cas9 mutated C4-2B colonies, strong blue staining was observed in nearly all cells indicating cellular senescence.

Androgen receptor(AR)

Binding

CHIP//Luciferase reporter assay

Chromatin immunoprecipitation (ChIP) assays were performed on the genomic CXCR7 promoter in LNCaP cells in the presence and absence of androgen. The promoter of prostate specific antigen (PSA) was used as a positive control for AR binding and showed a significant enrichment with androgen stimulation compared to androge...

EGFR

--

Western blot//Histochemical staining

We observed substantially reduced CXCR7-ARRB1 and increased CXCR7-ARRB2 interactions in the CXCR7-mutant LNCaP cell line compared to WT CXCR7 LNCaP cells. These data reveal that the lost protein region containing amino acids 114 to 243 altered protein-protein interactions necessary for the observed ARRB-EGFR-CXCR7 regu...

Human

HL

delay aging

28,596,572

Gene

0

1

0

1

0

1

0

TRMT9B

57604

protein coding

Htrm9L

Tumour sample

Colorectal cancer

Accelerate

Immunostaining//SA--gal activity assay

Although some inter-experiment variability was observed for the absolute levels of senescence, hTRM9Lexpressing tumour nodules were consistently higher in SA-¦Â-Gal activity and peaked 3 days after in vivo inoculation. Close to 80% of the hTRM9L proficient cells stained positive for SA-¦Â-Gal activity after 3 days and ...

LIN9//HIF1-a

Upregulation//Upregulation

Western blot//Immunostaining

We validated that the LIN9 transcript and protein is up-regulated 2-fold in hTRM9 expressing cells.First, we performed a quantitative analysis of HIF1-a protein levels in SW620, SW620-LacZ and SW620-hTRM9L expressing cells grown 3 days post inoculation on the CAM. We determined that HIF1-a protein levels were 2-fold hi...

--

Human

HL

delay aging

23,381,944

Gene

0

1

0

1

0

MYC

4609

protein coding

HT-1080

--

Cancer

Accelerate

SA--gal activity assay

The overexpression of c-Myc resulted in increased cellular senescence in transfected HT-1080 cells which was prevented by transducing the cultures with lentiviral-p30II (HA) or through the co-expression of FLAG-tagged TIGAR.

--

Human

L

delay aging

29,462,755

Gene

0

1

0

FBXO31

79791

protein coding

MCF-7

--

Aging

Accelerate

BrdU assay//SA--gal activity assay

we found that ectopic expression of FBXO31 in MCF7 cells promoted growth arrest, as evidenced by reduced proliferation and decreased DNA replication (BrdU incorporation), and induced senescence, as evidenced by positive staining for senescence-associated ¦Â-gal.

MDM2//p53//ATM

Downregulation//Upregulation//--

Western blot//Co-IP

The immunoblot shows that ectopic expression of FBXO31 resulted in decreased levels of MDM2, which, as expected, were accompanied by increased levels of p53 and p21.The presence of MDM2 in the FBXO31 immunoprecipitate, which was increased by lactacystin addition. The reciprocal coimmunoprecipitation experiment showed t...

--

Human

L

delay aging

26,124,108

Gene

0

1

0

1

0

SQSTM1

8878

protein coding

PaSC

--

Pancreatic ductal adenocarcinoma

Prevent

Flow cytometry//Knockdown//SA--gal activity assay//qRT-PCR

qPCR analysis corroborated the upregulation of these genes including IL-8, CXCL1, CXCL2, CCL2, and CCL20. This transcriptional change suggested an inflammatory and senescent phenotype of PaSCs. Flow cytometry analysis showed that FAP expression was increased in sqstm1 shRNA-transfected PaSCs. Consistently, ¦Â-galactosi...

--

Human

HL

delay aging

31,182,922

Gene

0

1

0

1

0

1

0

1

0

SAMHD1

25939

protein coding

HeLa

--

Aicardi¨CGouti¨¨res syndrome

Prevent

Flow cytometry//Knockdown//SA--gal activity assay//Western blot

Depletion of SAMHD1 in HeLa cells by RNA interference led to increased expression of p21. This was accompanied by a delay in cell cycle progression and signs of cellular senescence, as shown by increased ¦Â-galactosidase activity.

--

Human

HL

delay aging

24,445,253

Gene

0

1

0

1

0

1

0

1

0

TOP1

7150

protein coding

HCT116

--

Aging

Prevent

Clonogenic assay//Flow cytometry//Knockdown//SA--gal activity assay

We observed using clonogenic assays that sn38 induced a complete inhibition of cell proliferation. Using beta-galactosidase staining, we also noticed an induction of senescence following genotoxic treatment.control cells were synchronized in the G2 phase of the cell cycle after 48-72 hr.

Aurora-A

--

qRT-PCR//Western blot//Knockdown

Although this was the cell cycle stage when Aurora-A expression was supposed to be maximal, results indicated that the expression of the kinase was downregulated in response to sn38, both at the protein and mRNA levels.Finally, these experiments have also been repeated in a different colorectal cell line and sn38 also ...

--

Human

L

delay aging

20,682,043

Gene

0

1

0

1

0

1

0

1

0

TERT

7015

protein coding

U937

--

Atherosclerosis

Prevent

Knockdown//SA--gal activity assay//qRT-PCR

MPM isolated from first-generation TERT-deficient mice significantly upregulated senescence associated -galactosidase activity, an established biomarker of replicative senescence. Furthermore, TERT-deficient macrophages revealed increased transcript levels of several genes causally involved in replicative senescence,26...

--

NF-¦ÊB

Binding

CHIP

We next performed chromatin immunoprecipitation assays using primer pairs that cover the NF-KB site at 592/580 in the human TERT promoter to determine whether NF-KB subunits are recruited to the endogenous TERT promoter. These assays confirmed that LPS, oxLDL, and TNF- induce the recruitment of both NF-KB subunits to t...

Human

L

delay aging

21,106,948

Gene

0

1

0

1

0

1

0

SLC4A2

6522

protein coding

BEC

--

Primary biliary cholangitis

Prevent

Knockdown//SA--gal activity assay

Transfection of BEC with AE2-specific siRNA that reduced AE2 expression significantly increased the proportion of SA-¦Â-gal-positive cells (p < 0.05) and this effect was significantly inhibited by NAC (p < 0.05), indicating that the increased cellular senescence is indeed caused by the reduced level of AE2 expression.

--

Human

L

delay aging

27,592,379

Gene

0

1

0

1

0

FANCD2

2177

protein coding

Fancd2+/+ epithelial cell

Skin

Fanconi anemia

Accelerate

Knockdown//SA--gal activity assay

To test this hypothesis, we examined the level of senescence-associated (SA)-¦Â-galactosidase staining, a measure of in vivo senescence (Lin et al., 2010), in skin extracted from the TPA-exposed animals. Consistent with the reduced proliferation observed in TPA-treated Fancd2+/+ epithelial cells, we detected a higher a...

TAp63//USP1

Upregulation//--

CHIP//Western blot

Consequently, we performed chromatin immunoprecipitation (ChIP) assays to determine whether FANCD2-Ub could directly bind to the promoter region of TAp63. The promoter regions of the p63 gene have previously been analyzed (Buckley et al., 2011; Waltermann et al., 2003). We initially divided the promoter of TAp63 into s...

--

Human

HL

delay aging

23,806,336

Gene

0

1

0

1

0

PIP4K2A

5305

protein coding

BT-474

--

Breast cancer

Prevent

Immunostaining//Knockdown//SA--gal activity assay

We observed a significant increase in reActivate oxygen species (ROS), in oxygen consumption, and in ¦Â-galactosidase staining in the BT474 cells in response to knockdown of both PI5P4K¦Á and ¦Â consistent with ROS-induced senescence.Decrease in cell proliferation in response to knockdown of both PI5P4K¦Á and ¦Â.

--

PI3K-Akt

--

Western blot//Knockdown

This increase in AKT phosphorylation could be explained by an increase in PI-3,4,5-P3 levels in response to knockdown of both PI5P4Ka and b . Surprisingly, we observed a dramatic decrease in PI-3,4-P2 in the double-knockdown cells .The levels of INPP4B were virtually undetectable in BT474 cells prior to the knockdown o...

Human

HL

delay aging

24,209,622

Gene

0

1

0

1

0

1

0

PIP4K2B

8396

protein coding

BT-474

--

Breast cancer

Prevent

Immunostaining//Knockdown//SA--gal activity assay

We observed a significant increase in reActivate oxygen species (ROS), in oxygen consumption, and in ¦Â-galactosidase staining in the BT474 cells in response to knockdown of both PI5P4K¦Á and ¦Â consistent with ROS-induced senescence.Decrease in cell proliferation in response to knockdown of both PI5P4K¦Á and ¦Â.

--

PI3K-Akt

--

Western blot//Knockdown

This increase in AKT phosphorylation could be explained by an increase in PI-3,4,5-P3 levels in response to knockdown of both PI5P4Ka and b. Surprisingly, we observed a dramatic decrease in PI-3,4-P2 in the double-knockdown cells.The levels of INPP4B were virtually undetectable in BT474 cells prior to the knockdown of ...

Human

HL

delay aging

24,209,622

Gene

0

1

0

1

0

1

0

GNMT

27232

protein coding

HuH-7-GNMT,HuH-7-GFP,HepG2

--

Hepatocellular carcinoma

Accelerate

Flow cytometry//MTT assay//SA--gal activity assay

The growth rate of HuH-7-GNMT cells was significantly slower than that of HuH-7-GFP cells. Similar results were also observed in HepG2 cells overexpressing GNMT. Cell cycle analysis showed that, 36 h after the cells entered the cell cycle, the percentages of cells in the G2/M phase for HuH-7-GNMT cells and HuH-7-GFP ce...

DEPTOR

Binding

FRET-AB assay//Co-IP

Immunoprecipitation of either HAtagged DEPTOR or endogenous DEPTOR coprecipitated FLAG-tagged GNMT. In addition, we detected endogenous DEPTOR in GNMT immunoprecipitants prepared from mouse liver. The results showed that the FRET efficiency between full-length GNMT and DEP domains of DEPTOR decreased significantly. In ...

mTOR-Raptor

Activation

Western blot

The results showed that overexpression of GNMT led to increases of both 4E-BP phosphorylation and cell size. In addition, overexpression of DEPTOR in HuH-7-GNMT stable cells resulted in the neutralization of the effect of GNMT on 4E-BP phosphorylation.

Human

L

delay aging

22,160,218

Gene

0

1

0

1

0

1

0