Venkatachalam/aging_reg_dataset · Datasets at Hugging Face

SIRT1

23411

protein coding

BM-MSC

--

Osteoporosis

Prevent

BrdU assay//Colony formation assay//SA--gal activity assay//Western blot

Compared with cells from the vehicle-treated group, resveratrol-treated cells had a higher percentage of BrdU positive cells and numbers of ALP+ CFU-f colonies. Resveratrol-treated M-MSCs from WT mice had similar numbers of ALP+ CFU-f colonies as vehicle treated M-MSCs from Sirt1TG mice, and resveratrol-treated M-MSCs ...

Bmi1

Binding

Western blot//IP

The results showed that Sirt1 could bind to Bmi1.Immunoprecipitation with an anti-Bmi1 antibody showed a dose-dependent upregulation of Sirt1 protein expression associated with decreased expression of acetylated lysine. Western blot data from nuclear lysates demonstrated that the dose-dependent upregulation of Sirt1 wa...

--

Human

HL

delay aging

30,690,778

Gene

0

1

0

1

0

1

0

1

0

NAMPT

10135

protein coding

IMR-90

--

Aging

Accelerate

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

Inhibition of NAMPT by knockdown or by treatment with the small-molecule inhibitor FK86619 suppressed RAS-induced senescence at the time of initiation. Notably, NAMPT upregulation coincided with the upregulation of genes in the second, proinflammatory, SASP wave such as IL1B, IL6 and IL8.

--

Human

HL

delay aging

30,778,219

Gene

0

1

0

1

0

1

0

KDM4A

9682

protein coding

IMR-90

--

Aging

Prevent

Knockdown//SA--gal activity assay

Compared to cells transfected with siGFP, cells depleted of JMJD2A exhibited a flattened vacuolated morphology accompanied by a positive staining to the senescence-associated ¦Â-galactosidase assay(SA-¦Â-gal).However, the knockdown of JMJD2A led to the accumulation of PML nuclear bodies,another well- characterized sene...

CHD5

Binding

CHIP//qRT-PCR//Knockdown

Among the two putative JMJD2A-binding sites identified by ChIP-on-chip on the CHD5 promoter, only the site located at +741 was enriched by ChIP-qPCR.JMJD2A depletion also led to a concomitant increase of CHD5 mRNA and protein.We detected an increase of H3K9(me3) levels at the CHD5 promoter after depletion of JMJD2A .

p53

Downregulation

SA-¦Â-gal activity assay//Knockdown

Transfection of siRNAs targeting JMJD2A triggered senescence in p16-depleted cells but not in p53-depleted cells, suggesting that the senescence response triggered by decreased JMJD2A levels relies primarily on the p53 pathway. Ectopic expression of JMJD2A caused a significant decrease of both p53 and p21 in Ras-expres...

Human

L

delay aging

23,168,260

Gene

0

1

0

1

0

ABCC3

8714

protein coding

HEC-TR

--

Aging

Accelerate

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

This ABCC3-induced proliferation reduction was linked to senescence induction, as cells at p2 postinfection adopted the distinctive enlarged morphology of senescent cells and displayed both increased SA-¦ÂGal activity and induction of IL8 expression.

--

Human

L

delay aging

26,073,088

Gene

0

1

0

1

0

1

0

PIK3CA

5290

protein coding

MCF 10A/H

--

Breast cancer

Accelerate

Cell morphological analysis//SA--gal activity assay

Unexpectedly, we found that MCF-10A/H cells exhibited a significant increase in cell size after 96-h serum-starvation, which was accompanied with flat and enlarged morphology, suggesting cellular senescence might be induced in serum-starved MCF-10A/H cells. The fraction of SA-¦Â-gal-positive cells increased with the du...

MME

Upregulation

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

The cluster analysis showed that the mRNA level of membrane metallo-endopeptidase (MME) increased in MCF-10A/H cells compared to parental cells and the up-regulation was further enhanced when MCF-10A/H cells were serum-starved. Induction of MME was confirmed at both RNA and protein levels in serum-deprived MCF-10A/H ce...

PI3K-Akt-mTOR

--

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

GDC0941, a pan inhibitor of class I PI3K, significantly abrogated the induction of senescence represented by decreased SA-¦Â-gal-positive cells, which was consistent with the down-regulation of phosphorylated AKT at S473. Similar results were obtained with A66, a PI3K¦Á-selective inhibitor, which was consistent with th...

Human

HL

delay aging

30,671,946

Gene

0

1

0

1

0

ATF1

466

protein coding

Sarcoma-iPSC MEF

--

Clear cell sarcoma

Accelerate

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

EWS/ATF1-expressing sarcoma-iPSC MEFs ceased growth and changed morphology into a large and flat shape.The senescenceassociated ¦Â galactosidase (SA ¦Â-gal)-positive cell ratio was significantly higher in EWS/ATF1-expressing MEFs than in non-expressing MEFs,suggesting that EWS/ATF1 induces premature senescence in sarco...

--

Human

HL

delay aging

31,488,818

Gene

0

1

0

1

0

1

0

SERTAD1

29950

protein coding

MCF-7

--

Aging

Prevent

Knockdown//SA--gal activity assay

The SLP induced by doxorubicin was not observed in p34SEI-1¨C expressing MCF7 cells. Furthermore, the levels of various cytoplasmic marker proteins such as fibronectin and promyelocytic leukemia, which specifically decreases in senescent cells, were lower than control values in p34SEI-1¨Cexpressing cells, suggesting t...

--

Human

L

delay aging

19,903,772

Gene

0

1

0

1

0

NPM1

4869

protein coding

MEF

--

Aging

Accelerate

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

Fibroblasts that overexpressed NPM remained viable for several days but did not incorporate bromodeoxyuridine.Morphologically the cells became flat, enlarged and positive for acidic ¦Â-galactosidase (SA-¦Â-Gal), a marker of senescence.

p53

Upregulation

Cell counting//Western blot//qRT-PCR

The physical association and colocalization of NPM and p53, and its ability to induce cellular senescence in a p53-dependent manner, suggest that NPM might regulate p53 activity directly.GFP¨CNPM inhibited the growth of human WI38 cells and caused a marked upregulation in the amounts of p53, hdm2 and p21 proteins.Incre...

--

Human

L

delay aging

12,080,348

Gene

0

1

0

1

0

1

0

MDM2

4193

protein coding

LS8817

--

Cancer

Prevent

SA--gal activity assay//Western blot

It is well known that enforced expression of MDM2 does not increase its abundance in cycling cells; however, enforced expression did prevent the PD0332991-induced reduction in MDM2. Accumulation of phospho-Rb and cyclin A were also reduced.However, it prevented the CDK4i-induced accumulation of SA-¦Â-gal positive cells...

--

Human

L

delay aging

25,803,170

Gene

0

1

0

1

0

ID1

3397

protein coding

PC-3

--

Prostate cancer

Prevent

CCK-8 assay//Knockdown//SA--gal activity assay

Cell viability was decreased by more than 20% in siRNA-Id1 cells compared with that in nonspecific siRNA control cells, more than 30% of cells in siRNAId1 showed the appearance of enlarged blue cells in contrast to the siRNA control cells (P < 0.01).

--

Human

L

delay aging

20,881,502

Gene

0

1

0

1

0

1

0

NF1

4763

protein coding

--

Mice ear

Melanoma

Accelerate

Knockdown//SA--gal activity assay

Importantly, we found that deep dermal lesions derived from control Tyr::CreER T2 ; Braf CA/+ mice stained positive for senescence associated¨C¦Â-galactosidase, as has been shown in human nevi and in lesions within the Braf V600E - driven mouse model described by Dhomen and colleagues . However, senescence was not obse...

--

PI3K-Akt-mTOR

--

Western blot

Moreover,Nf1 mutations minimized the suppressive effects of Braf mutations on this pathway.Notably, we found that the PI3K inhibitor GDC-0941 prevented melanocytic hyperplasia in Tyr::CreER T2;Braf CA/+ ; Nf1 flox/flox mice,showing that Nf1 loss was mediating its effects in melanocytes, in part, by permitting or enhanc...

Human

L

delay aging

23,171,796

Gene

0

1

0

1

0

ICMT

23463

protein coding

Fibroblast

--

Hutchinson-Gilford progeria syndrome

Accelerate

Growth curve assay//Knockdown

As expected,Zmpste24?/? Icmt+/+ fibroblasts proliferated slowly and senesced prematurely. In contrast, Zmpste24?/? Icmthm/hm and Zmpste24?/? Icmt¡÷/¡÷ cells proliferated at rates similar to those of wildtype cells.

prelamin A

--

DAPI

prelamin A was mainly found at the nuclear rim in Zmpste24?/?Icmt+/+hepatocytes,colocalizing with LAP2b.In contrast,prelamin A in Zmpste24?/?Icmthm/hm hepatocytes was abundant in the nucleoplasm.

Akt-mTOR

--

Knockdown//Western blot

We observed higher levels of phosphorylated AKT and greater mTOR activation in Zmpste24?/? Icmthm/hm cell lysates than in Zmpste24?/? Icmt+/+ lysates, evident by increased phosphorylation of its downstream targets ribosomal protein S6 and 4E-BP1. Similar results were observed in comparisons of Zmpste24+/+Icmthm/hm and ...

Human

L

delay aging

23,686,339

Gene

0

1

0

1

0

SIRT1

23411

protein coding

HUVEC

--

Atherosclerosis

Prevent

Knockdown//SA--gal activity assay

We observed that the adenovirus-mediated SIRT1 knockdown directly induced senescence in young HUVECs. Conversely, SIRT1 overexpression significantly decreased SA-¦Â-gal activity in senescent HUVECs, suggesting that SIRT1 protects against endothelial replicative senescence.

PAI-1

Downregulation

Western blot//qRT-PCR//Knockdown

PAI-1 expression was dramatically enhanced after SIRT1 knockdown at both the mRNA and protein levels in young HUVECs, while SIRT1 overexpression markedly inhibited PAI-1 expression at both the mRNA and protein levels in senescent HUVECs.

--

Human

L

delay aging

25,040,736

Gene

0

1

0

1

0

SERPINE1

5054

protein coding

HUVEC

--

Aging

Accelerate

SA--gal activity assay

CPAI-Q123K, HPAI-RR, and the negative control PAI-L all failed to directly induce HUVEC senescence, whereas CPAI resulted in SA-¦Â-gal-positive staining in nearly 40% of HUVECs. Moreover, treatment of senescent HUVECs with the PAI-1 inhibitor PAI-039 significantly decreased the senescent cell ratio in a dose-dependent ...

--

Human

L

delay aging

25,040,736

Gene

0

1

0

CDKN2A

1029

protein coding

C6

--

Aging

Accelerate

Cell morphological analysis//Colony formation assay//SA--gal activity assay

The control cells surviving G418 selection in the colony formation assays were not altered morphologically, however we noticed the pCLp16 infected cells were flattened, large, or bi-polar. These morphological changes may suggest that the cells had entered senescence. only large or bipolar C6 cells infected with pCLp16 ...

--

Human

L

delay aging

11,983,028

Gene

0

1

0

1

0

1

0

DUSP16

80824

protein coding

PLC-PRF-5

--

Aging

Prevent

SA--gal activity assay

Intriguingly, the percentage of SA-¦Â-Gal-positive cells significantly increased upon DUSP16 silencing.

Rb

--

Western blot//Knockdown

In PLC/PRF/5 cells, we observed that decreased levels of Cyclin-dependent kinases (CDKs) upon DUSP16 silencing led to reduced phosphorylation of Rb,as well as reduced phosphorylation of Rb upon DUSP16 silencing.

p53

--

Western blot//Knockdown

Upon DUSP16 knockdown, p53 downstream effectors were dramatically up-regulated . we confirmed that p53 phosphorylation was increased upon DUSP16 knockdown.

Human

HL

delay aging

26,381,291

Gene

0

1

0

RAPGEF4

11069

protein coding

ESC

--

Decidualization of Human Endometrial Stromal Cell

Prevent

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

The intensity of SA-¦Â-Gal staining was significantly increased in the EPAC2 siRNA-treated group compared with the control.When the expression of p53 and p21 was examined in these cells, knockdown of EPAC2 suppressed p53 levels and increased p21 levels.Double knock-down of EPAC2 and p21 reduced the ratio of SA-¦Â-Gal...

CRT

--

Western blot//Knockdown//qRT-PCR

Consistent with the results of LC-MS/MS analysis, EPAC2 knock-down significantly suppressed CRT expression, regardless of the presence of cAMP analogs.real-time RT-PCR analysis showed that EPAC2 knock-down inhibited expression of CRT mRNA in each group, with or without cAMP analogs.

--

Human

L

delay aging

24,169,561

Gene

0

1

0

1

0

1

0

1

0

CALR

811

protein coding

ESC

--

Decidualization of Human Endometrial Stromal Cell

Prevent

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

The intensity of SA-¦Â-Gal staining was significantly increased in the CRT siRNA-treated group compared with the control.When the expression of p53 and p21 was examined in these cells, knockdown of CRT suppressed p53 levels and increased p21 levels.Double knock-down of CRT and p21 reduced the ratio of SA-¦Â-Gal-positiv...

--

Human

L

delay aging

24,169,561

Gene

0

1

0

1

0

1

0

1

0

CEBPB

1051

protein coding

PB-TRE,PB-CEBPB,LNCaP-shNTV

--

Prostate cancer

Accelerate

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

Cells expressing shCEBPB or shNTV both went into G1 cell cycle arrest when cultured in androgen depleted media (ADM).Compared to control PB-TRE, PB-CEBPB cells had a significantly increase in the number SA-¦Â-gal positive cells and the level of cell granularity, as assessed by side scatter.overexpression of C/EBP¦Â led...

--

Human

HL

delay aging

25,772,238

Gene

0

1

0

1

0

1

0

1

0

JPT1

51155

protein coding

A549,HUVEC

--

Cancer

Prevent

CCK-8 assay//EdU assay//Knockdown//SA--gal activity assay//qRT-PCR

All three cell lines showed decreased proliferation rate and increased percentage of senescence-associated SA-¦Â-Gal positive cells.Second, decreased DNA synthesis rate was observed in HN1-KD cells by the EdU incorporation assay.LMNB1, a senescence marker indicating nuclear changes of senescent cells ,showed signific...

--

Human

HL

delay aging

31,257,225

Gene

0

1

0

1

0

1

0

1

0

1

0

HNRNPA1

3178

protein coding

HUVEC,A549

--

Cancer

Prevent

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

HNRNPA1-KD led to a higher percentage of positive SA-¦Â-Gal stained cells and slower cell growth rate in both cell types. Besides, HNRNPA1-KD HUVECs and A549 cells also showed arrested G2/M phase, decreased LMNB1 expression, increased ROS production, and altered expression of senescence-associated molecular markers (in...

HN1-L

--

qRT-PCR//Knockdown

Knockdown of HNRNPA1 or HNRNPM could promote the relative expression of HN1-L compared to total expression (HN1-L and HN1-S, labelled as HN1-T), but HNRNPA1 demonstrated the maximun effect, so HNRNPA1 was choosed for further investigation. the increased L/T ratio in HNRNPA1-KD cells could be reversed with HNRNPA1 overe...

--

Human

HL

delay aging

31,257,225

Gene

0

1

0

1

0

1

0

1

0

1

0

1

0

MYC

4609

protein coding

hTERT-immortalized WRN?/? Fibroblast strains AG00780,hTERT-immortalized WRN?/? Fibroblast strains AG03141

--

Aging

Accelerate

Knockdown//Microarray//SA--gal activity assay

However, within 2¨C3 passages, ¡«30%¨C70% of the WRN¨C/¨C cells expressed senescence-associated (SA-) ¦Â-galactosidase and lost proliferative capacity. The senescent phenotype in c-myc-transduced WRN¨C/¨C cells was also confirmed at the gene expression level by microarray analysis, which demonstrated elevated expressio...

WRN

Binding

CHIP//qRT-PCR//Co-IP

Comparable results demonstrating increased WRN A and B site binding by MYC were obtained in four different cell lines expressing deregulated c-myc.In vivo binding of MYC to the WRN promoter and a modest but consistent elevation in histone H4 acetylation, as observed for other MYC-target genes (Frank et al. 2001), was a...

--

Human

HL

delay aging

12,842,909

Gene

0

1

0

1

0

1

0

WRN

7486

protein coding

hTERT+ Fibroblast

--

Aging

Prevent

Knockdown//SA--gal activity assay

WRN-depleted cells proliferated poorly compared to empty vector or cells expressing a control RNAi . MYC overexpression failed to rescue theproliferative capacity of WRN-depleted cells and led to a significant increase in the percentage of SA-¦Â-gal-positive cells.

--

Human

HL

delay aging

12,842,909

Gene

0

1

0

1

0

CHEK2

11200

protein coding

BJ,Fibroblast,iG4 Terc?/?Fibroblast

Colon

Telomere dysfunction

Accelerate

Immunostaining//Knockdown//Western blot

Infection of late©\passage, primary human BJ fibroblasts with lentiviral vectors expressing a CHK2©\directed shRNA confirmed that CHK2 knockdown abrogated the induction of senescence, resulting in positive selection of CHK2©\knockdown cells and improved proliferation rates of human fibroblast cultures at late passage. ...

--

Human

L

delay aging

20,577,265

Gene

0

1

0

1

0

1

0

TP53

7157

protein coding

HSC

--

Aging

Accelerate

Cell counting//DAPI staining//Ki67 staining//RT-PCR//SA--gal activity assay

We found a time-dependent increase in TP53 mRNA level expression upon Dox removal. We also found increased expression of CDKN2A (encoding p16INK4A) and CDKN1A (encoding p21), genes important in inducing cell cycle arrest and senescence25, after Dox was withdrawn. HSCs after Dox removal showed increased SA-¦Â-gal (senes...

--

Human

L

delay aging

30,962,418

Gene

0

1

0

1

0

1

0

1

0

1

0

FASN

2194

protein coding

HSC

--

Aging

Accelerate

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

FASN knockdown in senescent HSCs prevented the senescent-induced cell cycle arrest, in addition to preventing the upregulation of different markers of senescence such as SA-¦Â-gal activity, p53, p16 and p21. Notably, FASN knockdown also inhibit the increase in the expression of mRNA levels of SASP factors IL1A, IL1B an...

--

mTOR

--

Western blot

To our surprise,mTOR activity was repressed during senescence as shown by a decrease in the phosphorylation levels of some of its downstream targets: S6, 4EBP1 and AKT. Remarkably, senescent cells treated with C75 were able to restore mTOR signalling at levels similar to control.

Human

L

delay aging

30,962,418

Gene

0

1

0

1

0

1

0

1

0

TRPM7

54822

protein coding

BxPC-3,PANC-1

--

Pancreatic cancer

Prevent

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

Consistent with the observations in the micrographs with phase contrast, bright field examination reveals that both BxPC-3 and PANC-1 cells with targeted knock down of TRPM7 expression exhibit morphological features indicative of a senescent phenotype. In the BxPC-3 and PANC-1 cells transfected with anti-TRPM7 siRNA b...

WRN

--

qRT-PCR

In TRPM7-deficient PANC-1 cells, the mRNA levels of p16INK4A and WRN were elevated whereas that of p27CDKN1B remained unaltered. Similarly, in TRPM7-deficient BxPC-3 cells, the mRNA levels of p16INK4A and WRN were elevated by 1.4-fold and 26%, respectively.

--

Human

L

delay aging

22,166,235

Gene

0

1

0

1

0

1

0

1

0

HMGB2

3148

protein coding

IMR-90

--

Aging

Prevent

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

We validated that HMGB2 expression was decreased at both the mRNA and protein levels during senescence of normal primary human embryonic fibroblast IMR90 cells induced by oncogenic RAS.knockdown or knockout of HMGB2 induced senescence in IMR90 cells .

C/EBP-¦Â//SASP

Binding//--

Knockdown//CHIP-seq//CHIP//qRT-PCR

C/EBP-¦Â is a direct target gene of HMGB2 in senescent cells, and knockdown of HMGB2 decreased C/EBP-¦Â gene expression.Loss of HMGB2 allows for spreading of heterochromatin marks and promotes the inclusion of SASP gene loci into SAHF, which in turn represses SASP gene expression.

--

Human

HL

delay aging

27,799,366

Gene

0

1

0

1

0

1

0

1

0

SMARCD1

6602

protein coding

TIG-1,Hepatocyte,Hepatocyte

--

Aging

Prevent

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

Results show that the relative number of cells with increased senescence-associated ¦Âgalactosidase (SA-¦Â-Gal) activity, p16/p21 expression, and phospho p38 (p-p38) expression is increased in SMARCD1-silenced TIG1 cells.In contrast, cellular senescence was shown to be suppressed in senescent TIG-1 cells (61 PDL) where...

--

Human

L

delay aging

28,868,154

Gene

0

1

0

1

0

1

0

HSP90AA1

3320

protein coding

IMR-90,HFF

--

Lung cancer

Prevent

Knockdown//SA--gal activity assay

Regardless of the concentration, GA treatment doubled or tripled the amount of ¦Â-galactosidase-positive senescent IMR90 fibroblasts and HFFs compared to controls .As expected, HSP90¦Á or ¦Â knockdown by isoform-specific HSP90 siRNAs accelerated cellular senescence.

p14

--

Western blot

GA treatment or HSP90 ablation induced an increase in p14ARF protein levels and prolonged the half-life of the p14ARF protein under cycloheximide (CHX) treatment in the human cervical cancer cell line HeLa.

--

Human

HL

delay aging

27,793,846

Gene

0

1

0

1

0

HSP90B1

7184

protein coding

IMR-90,HFF

--

Lung cancer

Prevent

Knockdown//SA--gal activity assay

Regardless of the concentration, GA treatment doubled or tripled the amount of ¦Â-galactosidase-positive senescent IMR90 fibroblasts and HFFs compared to controls.As expected, HSP90¦Á or ¦Â knockdown by isoform-specific HSP90 siRNAs accelerated cellular senescence.

p14

--

Western blot

GA treatment or HSP90 ablation induced an increase in p14ARF protein levels and prolonged the half-life of the p14ARF protein under cycloheximide (CHX) treatment in the human cervical cancer cell line HeLa.

--

Human

HL

delay aging

27,793,846

Gene

0

1

0

1

0

SIRT6

51548

protein coding

HUVEC

--

Aging

Prevent

BrdU assay//Immunostaining//SA--gal activity assay

SIRT6-silenced cultures showed decreased rates of proliferation and a reduction in the cell fraction passing through the S-phase.SIRT6-silenced cultures also displayed an increase in the proportion of SA-¦Â-gal+ cells.In SIRT6-depleted HUVEC, there was a significant increase in ¦ÃH2AX foci.

--

p21

--

Western blot

This analysis showed higher levels of p21 expression in SIRT6-depleted cells compared with controls.

Human

L

delay aging

23,201,774

Gene

0

1

0

1

0

1

0

MIF

4282

protein coding

MSC

--

Myocardial infarction

Prevent

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

MIF-siRNA treatment of young MSCs significantly downregulated MIF expression, while it significantly elevated p53 and p21 expression. Furthermore, MIF-siRNA treatment remarkably increased the number of SA-¦Â-gal-positive cells among young MSCs.While the overexpression of MIF in aged MSCs enhanced MIF expression, it red...

Beclin1//LC3-I/II//p62

Upregulation//Upregulation//Downregulation

Western blot

Autophagy has recently been found to inhibit cellular senescence.Overexpression of MIF in aged MSCs significantly induced autophagy, as manifested by the elevated expression of Beclin1 and LC3I/II and the reduced expression of p62.

--

Human

L

delay aging

31,881,006

Gene

0

1

0

1

0

1

0

ZBTB48

3104

protein coding

pMSC

--

Aging

Accelerate

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

Overexpression of TZAP in P2 pMSCs resulted in an increase in the percentage of SA-¦Â-gal-positive cells by 17% (from 6 to 23%). Western blot analysis showed that compared to the control vector, TZAP over-expression in pMSCs significantly increased the protein levels of P21 and P16. Consistent with this finding, qRT-PC...

--

p53

Upregulation

Western blot

After overexpression of TZAP in pMSCs, western blot analysis showed that overexpression of TZAP led to increased levels of ARF, P53 and P21 but decreased levels of MDM2 compared to those in pMSCs transduced with the control vector. In contrast, knockout of TZAP in pMSCs decreased ARF, P53, and P21 levels but increased ...

Human

HL

delay aging

30,845,965

Gene

0

1

0

1

0

1

0

NFATC1

4772

protein coding

prostate epithelial cell

--

Prostate cancer

Prevent

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

There was a marked decrease in the expression of the senescence marker p21 in PCre/+;RT/+;TN/+;Ptenfl/fl samples when compared with the PCre/+;Ptenfl/fl mice. p21 staining was predominantly nuclear in PCre/+;Ptenfl/fl prostates (63.6 ¡À 7.95%). In contrast, nuclear p21 expression was absent in PCre/+;RT/+;TN/+;Ptenfl/f...

--

PTEN-AKT

Activation

Immunostaining

Interestingly, all double mutants (PCre/+;RT/+;TN/+;Ptenfl/fl) with both PTEN deficiency and NFATc1 activation developed significantly larger tumors in all prostate lobes when compared with mice of the same age with either Pten deficiency or NFATc1 activation alone . The average prostate weight in double mutants (6026....

Human

HL

delay aging

26,477,312

Gene

0

1

0

1

0

1

0

MAD2L1

4085

protein coding

MKN45

--

Gastric cancer

Prevent

SA--gal activity assay//qRT-PCR

With this experiment, we determined that the fraction of SA-¦Â-gal-positive cells increases 3d after Mad2 depletion. When we analyzed its activation after 72 h of PTX treatment, we observed an increase in p53 mRNA levels in cells lacking Mad2.IL-6 (and not IL-8) expression was attenuated when Mad2 was decreased.

--

Human

L

delay aging

25,483,095

Gene

0

1

0

1

0

BUB1B

701

protein coding

MKN45

--

Gastric cancer

Prevent

SA--gal activity assay//qPCR

With this experiment, we determined that the fraction of SA-¦Â-gal-positive cells increases 3d after BubR1 depletion. When we analyzed its activation after 72 h of PTX treatment, we observed an increase in p53 mRNA levels in cells lacking BubR1. Both IL-6 and IL-8 mRNA levels were increased during senescence in the abs...

--

Human

L

delay aging

25,483,095

Gene

0

1

0

1

0

NUPR1

26471

protein coding

A549,H460

--

Lung cancer

Prevent

BrdU assay//Colony formation assay//Flow cytometry//Knockdown//SA--gal activity assay//Western blot

In this regard, NUPR1 depletion in A549 or H460 cells caused a marked increase in the number of GLB1 (galactosidase beta 1)-positive cells. Consistent with the induction of GLB1, NUPR1 depletion induced G0/G1 cell cycle arrest, with significant upregulation of the key cell cycle inhibitors CDKN1A/p21Cip1 and CDKN1B/ p2...

--

Human

HL

delay aging

29,130,426

Gene

0

1

0

1

0

1

0

1

0

1

0

1

0

HRAS

3265

protein coding

IMR-90

--

Cancer

Accelerate

SA--gal activity assay//Western blot

Cells infected with the retrovirus expressing HRASG12V fail to proliferate and stained positive for senescence-associated ¦Â-galactosidase (SA-¦Âgal) activity.

--

Human

HL

delay aging

24,618,719

Gene

0

1

0

1

0

CUX1

1523

protein coding

IMR-90

--

Cancer

Prevent

SA--gal activity assay//Western blot

Co-expression of p200 CUX1 enabled RAS expressing cells to proliferate normally and prevented SA-¦Âgal activity.

OGG1

Activation

Western blot

The enzymatic activity of OGG1 was greatly stimulated by recombinant CUX1 proteins containing one or more Cut repeat domain(s): CR2CR3HD, CR3HD, and CR1CR2.

--

Human

HL

delay aging

24,618,719

Gene

0

1

0

1

0

ASXL1

171023

protein coding

MEF

--

Aging

Prevent

Cell morphological analysis//DAPI staining//Microarray//SA--gal activity assay//SAHF//Western blot//qRT-PCR

SA-¦Â-gal staining was significantly greater in two different passages of Asxl1-null MEFs than in WT MEFs. Consistently, more SAHF were formed in Asxl1-null MEFs as determined by DAPI staining.More senescence was induced at passage 6 of Asxl1-null MEFs because of growth retardation in the later stages. In addition, As...

E2F//EZH2

--//--

qRT-PCR//Co-IP

Most of the E2F target genes were significantly down-regulated in Asxl1-null.To explore the link between ASXL1 and EZH2,we first measured the physical interaction by co-IP analysis. As reported previously, Flag-EZH2 interacts with endogenous ASXL1.

Akt-E2F

--

Western blot//CHIP

A significant decrease in p27Kip1 phosphorylation was observed in Asxl1-null MEFs, which was likely due to Akt inactivation. As shown by IP assays using HEK293 cells treated with IGF-1, we demonstrated that p27Kip1 interacts with both ASXL1 and AKT1 regardless of IGF-1¨Cinduced AKT phosphorylation. Consistent with rep...

Human

HL

delay aging

28,701,722

Gene

0

1

0

1

0

1

0

1

0

1

0

1

0

1

0

RELA

5970

protein coding

Human low-grade PanIN cell

Pancreata

Pancreatic ductal adenocarcinoma

Accelerate

SA--gal activity assay//Western blot//qPT-PCR

Quantification of SA-¦Â-Gal¨Cpositive cells in low-grade mPanIN lesions from Kras and Kras RelA mice demonstrated loss of SA-¦Â-Gal activity in Kras RelA mPanIN.In addition, the senescence marker decoy receptor 2 (DCR2; also known as TNFRSF10D) was significantly lower in Kras RelA pancreata than in Kras pancreata on bo...

CXCL1

--

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

Of the 40 cytokines and chemokines represented in this panel, CXCL1 (also known as KC) was most robustly downregulated in PDEC Kras treated with JSH-23. The decrease in CXCL1 protein levels was corroborated by an increased SA-¦Â-Gal activity in PDEC Kras incubated with CXCL1 for 48 hours .In Kras pancreata, Cxcl1 mRNA ...

--

Human

HL

delay aging

27,454,298

Gene

0

1

0

1

0

1

0

NTN4

59277

protein coding

U251MG,pcDNA3

--

Glioblastoma

Prevent

SA--gal activity assay

We observed significantly fewer senescent NTN4-overexpressing cells compared with mock control cells.Thus, NTN4 overexpression delayed U251MG cell senescence induced by H2O2.

--

Human

HL

delay aging

30,514,230

Gene

0

1

0

EGF

1950

protein coding

U251MG

--

Glioblastoma

Prevent

SA--gal activity assay

On the 4th day after H2O2 treatment, we observed less senescence in U251MG cells treated with EGF compared with non-EGF treated cells. On the 7th day after H2O2 treatment, the number of senescent cells in the EGF treatment group was significantly less than that in the non-treatment control group.There was a significant...

NTN4

Upregulation

qRT-PCR//Immunostaining

We observed that NTN4 expression were significantly increased upon EGF stimulation at both mRNA level and protein level.

--

Human

HL

delay aging

30,514,230

Gene

0

1

0

COPS5

10987

protein coding

MEF

--

Cancer

Prevent

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

Under the microscope, 4OHT©\treated cells appeared flatter, a typical feature of senescent cells. We, therefore, assayed for senescence©\associated (SA) ¦Â©\galactosidase (Gal) activity, another marker of premature senescence.Lower panels show that 4OHT©\treated CSN5f/©\p53?/?Ras+CRE©\ER MEFs were positive for SA©\¦Â©\...

--

PI3K-Akt

--

Western blot//Knockdown

Although the total expression levels of ERK1, ERK2, and Akt were maintained, their activating phosphorylation was modulated by knockout of the CSN5 gene. The Activate form of ERK1 and 2 was reduced, whereas the activating phosphorylation of Akt (serine 473 and threonine 308) was increased after treatment with 4OHT. Fur...

Human

L

delay aging

23,127,558

Gene

0

1

0

1

0

1

0

CNOT6

57472

protein coding

MCF-7

--

Aging

Prevent

Knockdown//SA--gal activity assay

Consistent with the role of IGFBP5, knockdown of Ccr4a/Ccr4b caused a significant increase in senescence-associated ¦Â-galactosidase staining as compared with control or Caf1a/Caf1b knockdown.

IGFBP5

--

Knockdown//qRT-PCR

We confirmed enhanced expression of IGFBP5 (approximately threefold), CLEC3A (approximately threefold), SEMA3E (approximately twofold), MAPK10 (approximately twofold), CDH18 (approximately twofold), and LMO3 (approximately eightfold) upon Ccr4a/Ccr4b knockdown.

p53

--

Western blot//Knockdown

Interestingly, while the overall levels of both total p53 as well as p53 acetylated at Lys-120 were significantly increased in Ccr4a/Ccr4b knockdown cells, the fraction of p53 acetylated at Lys-120 was not increased.

Human

HL

delay aging

21,233,283

Gene

0

1

0

1

0

CNOT6L

246175

protein coding

MCF-7

--

Aging

Prevent

Knockdown//SA--gal activity assay

Consistent with the role of IGFBP5, knockdown of Ccr4a/Ccr4b caused a significant increase in senescence-associated ¦Â-galactosidase staining as compared with control or Caf1a/Caf1b knockdown.

IGFBP5

--

Knockdown//qRT-PCR

We confirmed enhanced expression of IGFBP5 (approximately threefold), CLEC3A (approximately threefold), SEMA3E (approximately twofold), MAPK10 (approximately twofold), CDH18 (approximately twofold), and LMO3 (approximately eightfold) upon Ccr4a/Ccr4b knockdown.

p53

--

Western blot//Knockdown

Interestingly, while the overall levels of both total p53 as well as p53 acetylated at Lys-120 were significantly increased in Ccr4a/Ccr4b knockdown cells, the fraction of p53 acetylated at Lys-120 was not increased.

Human

HL

delay aging

21,233,283

Gene

0

1

0

1

0

RBM38

55544

protein coding

MEF

--

Lymphoma

Prevent

Knockdown//SA--gal activity assay

We showed that the number of cells stained positive with senescence-associated ¦Â-galactosidase (SA-¦Â-gal) was markedly increased by lack of RNPC1 regardless of DNA damage . Quantitative analysis indicated that SA-¦Â-gal-positive cells were increased by threefold to eightfold upon loss of RNPC1 (47.5% in RNPC1?/? MEFs...

--

p53

Downregulation

Western blot

We showed that p53 was highly induced by RNPC1 deficiency, especially upon treatment with doxorubicin, consistent with the observation. Similarly, transient expression of RNPC1a, but not RNPC1b, inhibited p53 expression in a dose-dependent manner. Furthermore, we showed that upon treatment with doxorubicin or nutlin-3,...

Human

L

delay aging

21,764,855

Gene

0

1

0

1

0

PYGL

5836

protein coding

U87

--

Cancer

Prevent

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

Analysis of the cell-cycle profile after PYGL knockdown in U87 cells revealed a higher proportion of cells in G1 phase with concomitant decreases in both S phase and G2/M phase, as compared to control cells.Following PYGL depletion, U87 cells underwent characteristic morphological changes (i.e., enlargement and flatten...

--

p53

--

Knockdown//Western blot//Cell counting

Knockdown of p53 prevented the decreased growth rate phenotype normally associated with PYGL depletion.

Human

L

delay aging

23,177,934

Gene

0

1

0

1

0

1

0

1

0

1

0

ENO1

2023

protein coding

CFPAC-1

--

Pancreatic cancer

Prevent

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

The cell-cycle profile analysis after 24 h serum deprivation revealed a significant increase in the number of ENO1-silenced cells in G2/M phase, a concomitant decrease of cells in G1 phase and no difference in the number of cells in S phase .there was a decrease in expression of the negative regulator of the cyclin D/C...

--

Human

L

delay aging

26,734,996

Gene

0

1

0

1

0

1

0

1

0

NCOA4

8031

protein coding

MEF

--

Aging

Prevent

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

NCOA4?/? cells showed increased activation of the apical DDR kinases ATM and ATR, accumulation of nuclear foci stained for pS/TQ ATM/ATR substrates, and increased phosphorylation of p53 on S15. Furthermore, NCOA4?/? cells displayed an increased number of ¦Ã-H2AX- and 53BP1-positive cells compared to NCOA4+/+ MEFs.Consi...

--

Human

L

delay aging

24,910,095

Gene

0

1

0

1

0

1

0

1

0

KLF6

1316

protein coding

LN-229,BTSC233

--

Glioblastoma

Accelerate

Flow cytometry//SA--gal activity assay

Prolonged expression of KLF6-wt, but not KLF6-sv1, induced a senescent-like phenotype in both LN229 and BTSC23 cells, highlighted by ¦Â-galactosidase staining. Cell cycle analysis revealed accumulation of cells in phase G1¨CG0 and concomitant reduction of cells in phases S and G2/M, upon KLF6-wt expression.In contrast,...

--

NF-¦ÊB

Downregulation

Western blot

Downregulation of NF-¦ÊB targets MMP9, OLIG2 and YKL40 was confirmed by western blot.

Human

HL

delay aging

28,166,199

Gene

0

1

0

1

0

ABI3BP

25890

protein coding

GBC

--

Gallbladder cancer

Accelerate

EdU assay//SA--gal activity assay//Transwell assay//Western blot

The results demonstrated that compared with cells manipulated with vector-NC, cells manipulated with ABI3BP-vector displayed markedly enhanced ability of cell viability, weakened abilities of migration and invasion and promoted SA-¦Â-gal activity, as well as significantly down-regulated expression of Ki67 and PCNA.

--

Human

HL

delay aging

31,174,563

Gene

0

1

0

1

0

1

0

1

0

ATM

472

protein coding

DLD1,HCT116

--

Colorectal cancer

Prevent

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

Intriguingly, cell cycle analysis showed that ATM deletion induced a significant G2/M arrest of DLD1 and HCT116 cells under normal conditions.Moreover, we observed a significantly higher number of senescent ATM-/- cells compared with senescent ATM+/+ cells, as determined by SA-¦Â-gal staining .

B56¦Ã2

Binding

Western blot//Co-IP

Indeed,western blot analysis showed that B56¦Ã2 expression was significantly increased in ATM-/-cancer cells.Intriguingly, the coimmunoprecipitation experiments showed that ATM and B56¦Ã2 co-immunoprecipitated reciprocally.

Chk1-p53-p21

--

Western blot//Knockdown

The results showed that in ATM-/- cells, Cdc2 phosphorylation on Tyr15, which is indicative of decreased Cdc2 activity, was significantly increased . In addition, the phosphorylation of the upstream regulator Chk1 was significantly increased in ATM-/- cells, whereas the phosphorylation of Chk2 was not altered . In acco...

Human

HL

delay aging

28,093,285

Gene

0

1

0

1

0

1

0

ASAH1

427

protein coding

A375

--

Melanoma

Prevent

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

Only 2% of ASAH1-null cells entered the G2 phase, compared to 25% scramble-treated control cells. The remaining ASAH1-null cells were found in G1 (63%) or S (35%) phase. Similarly, ASAH1 deletion was accompanied by the appearance of a phenotype characterized by senescence-like cell morphology and accumulation of senes...

--

Human

L

delay aging

28,785,021

Gene

0

1

0

1

0

1

0

1

0

RHEB

6009

protein coding

Articular Chondrocyte

Bone

Osteoarthritis

Prevent

DAPI staining//SA--gal activity assay

RHEB- 9 overexpression not only recovered the morphology of the DCs, but also reduced senescence by 10 35¨C40 %. RHEB-overexpression also decreased ROS levels.

COL2A1//SOX9

Upregulation//Upregulation

Western blot

Importantly, 11 RHEB -overexpression increased the level of COL2A1, which was almost negligible in non-transfected DCs. SOX9 expression also increased with RHEB -overexpressing DCs.

--

Human

L

delay aging

31,229,684

Gene

0

1

0

1

0

AGER

177

protein coding

--

Lung

Aging

Prevent

Histological staining//Immunofluorescence//Knockdown//SA--gal activity assay

The absence of RAGE was associated with an accumulation of fibrotic tissue (as evidenced by Masson's trichrome staining) and senescent lesions, as evidenced by ¦Â-Gal-staining . The accumulation of these senescent lesions was also observed in other tissues of RAGE?/? mice.When markers of senescence associated cellular ...

--

Human

L

delay aging

28,977,635

Gene

0

1

0

1

0

1

0

1

0

SIRT1

23411

protein coding

ECFC

--

Preterm

Prevent

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

Twenty-four hours after transient transfection, SIRT1 overexpression was associated with a significant decrease in the level of the senescence-associated p16INK4a protein;Consistently,transfection of PT-ECFCs with the SIRT1 vector significantly reduced SA-¦Â-gal activity and senescence associated morphological changes...

--

Human

L

delay aging

24,518,759

Gene

0

1

0

1

0

1

0

1

0

FGF21

26291

protein coding

BVSMC

--

Cerebrovascular aging

Prevent

SA--gal activity assay//Western blot

Treatment of recombinant FGF21 (100 nM) significantly attenuated the positive area of SA-¦Â-gal staining;FGF21 treatment decreased the NBS1.

p21//TRF2

Downregulation//Upregulation

Western blot

FGF21 also inhibited the induced p21 expression by AngII.Siah-1 is an E3 ubiquitin ligase degrading TRF2£¬These results suggest that FGF21 enhances TRF2 expression via inhibiting Siah-1 signaling in hBVSMCs.Interestingly, FGF21 partly but significantly inhibited the upregulation of ROS and superoxide anion induced by A...

p53//Siah-1//AMPK

Downregulation//Downregulation//Activation

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

FGF21 supplement substantially depressed the both the total p53 and phospho-p53 levels induced by AngII £»FGF21 inhibited Siah-1 expression induced by AngII.FGF21 markedly increased phosphorylation of AMPK in hBVSMCs.SA-¦Â-gal staining assay showed that blockade of AMPK activation by specific inhibitor of AMPK Compound...

Human

L

delay aging

27,364,911

Gene

0

1

0

1

0

SIRT1

23411

protein coding

Clara

Lung

Chronic obstructive pulmonary disease

Prevent

SA--gal activity assay//Western blot

We found that the level of SIRT1 was decreased, whereas senescence-associated ¦Â-gal activ-ity and p21 expression were increased in lungs of COPD patients compared with nonsmokers.CS exposure significantly increased the levels of prosenescent proteins (i.e., p21, p16, and p53) and SA¨C¦Â-gal activity in lungs of Sirt1+...

FOXO3//p21

--//--

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

Foxo3¨C/¨C mice exhibited heightened levels of p21, p16, p27, and SA¨C¦Â-gal activity in lungs in response to CS exposure.However, there was no significant change in SA¨C¦Â-gal activity in lungs of p21¨C/¨C mice in response to CS exposure, or along with sirtinol treatment.Moreover, FOXO3 acetylation was increased in Si...

--

Human

L

delay aging

22,546,858

Gene

0

1

0

1

0

IHH

3549

protein coding

B-MSC

--

Aging

Prevent

Cell morphological analysis//Colony formation assay//Flow cytometry//PI staining//RT-PCR//SA--gal activity assay//Western blot

Surprisingly, the count of BMSC cells stained by SA-¦Â-gal stain increased in cells treated with IHH siRNA.Consistently, aging-related genes, p16, p53, SA-¦Â-gal, and mTOR were downregulated after treatment with rIHH.The IHH siRNA transfected BMSC showed more transparency, slight enlargement,and decreased in cell count...

--

ROS-mTOR-4EBP1

Downregulation//--

Western blot//Flow cytometry//Colony formation assay//Knockdown

We observed down-regulation of P53 and P16 associated with inhibition of mTORand ROS pathways.The cell cycle results showed that inhibition of mTOR and ROS pathways restricted the G0/G1 cell cycle arrest caused by IHH silencing .The colony forming ability of BMSC caused by IHH knockdown was improved after inhibition of...

Human

L

delay aging

32,235,006

Gene

0

1

0

1

0

1

0

1

0

1

0

1

0

1

0

NAMPT

10135

protein coding

Adipose stromal cell

Adipose

Aging

Prevent

Lifespan assay

We started injecting EVs purified from young-to-middle age (4¨C12-month-old) mice once a week into female mice at 26 months of age. supplementation with EVs purified from young-to-middle-aged mice significantly extended the lifespan of aged mice.

--

Human

L

delay aging

31,204,283

Gene

0

1

0

CALCA

796

protein coding

EPC

Blood

Aging

Prevent

SA--gal activity assay//Telomerase activity assay

CGRPI lentivirus transduction significantly reduced SA-¦Â-gal positive senescent cells and elevated the activity of telomerase in AngII-treated EPCs.

Klotho

Upregulation

Western blot//qRT-PCR

Interestingly, the levels of both Klotho mRNA and secreted Klotho protein were remarkably increased by CGRPI over-expression.

--

Human

HL

delay aging

20,832,068

Gene

0

1

0

1

0

ATG7

10533

protein coding

keratinocyte

Skin

Aging

Prevent

Microarray

PQ treatment induced a transcriptional signature of strong cell cycle arrest and DNA damage signaling in the Atg7 deficient cells.

p53//p21//CDK1//H2AX

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

Western blot//qRT-PCR//Immunostaining

p53 and the downstream mediator p21 were induced by PQ on mRNA and protein level, and the induction was increased in the knockouts on protein level for both proteins.Using qPCR we could verify that the knockout cells showed higher baseline expression of Cdk1.Using WB we could show that this was reflected on protein lev...

--

Human

HL

delay aging

28,012,437

Gene

0

1

0

FOXQ1

94234

protein coding

HUCMSC

Umbilical cord

Alzheimer's disease

Prevent

CCK-8 assay//Cell morphological analysis//PI staining//SA--gal activity assay//Western blot//qRT-PCR

Cell viability was significantly enhanced in the P15-FOXQ1 group compared with that in the P15-vector group on day 4.Meanwhile, the morphology of cells in the P15-FOXQ1 group was changed slightly compared with those in the P3 group,with the spindle shape maintained in most cells. The number of SA-¦Â-gal-positive cells ...

--

Human

L

delay aging

29,500,491

Gene

0

1

0

1

0

1

0

1

0

1

0

1

0

KNDC1

85442

protein coding

HUVEC

Umbilical cord

Aging

Accelerate

SA--gal activity assay

The number of positive SA-¦Â-Gal staining observed in the HUVECs following the transfection of the KNDC1?adenovirus vector significantly increased when compared with that in the control group.

--

p53

Upregulation

Western blot

However, a significant increase in the expression of p-p53 was observed in HUVECs that overexpressed KNDC1 when compared with the NT-adenovirus-transfected control cells.

Human

L

delay aging

29,568,929

Gene

0

1

0

FOXO3

2309

protein coding

HUC-F2

--

Aging

Prevent

SA--gal activity assay//qRT-PCR

Proliferative potential and senescence-associated ¦Â-galactosidase (SA-¦Â-Gal) activity were then monitored. Our results clearly showed that the dominant Activate form of FOXO3a (FOXO3aTM) significantly promoted proliferation and inhibited the onset of replicative senescence in HUC-F2 cells in a manner similar to SIRT1...

c-Myc//hTERT

Upregulation//Upregulation

Luciferase reporter assay//qRT-PCR

We found that FOXO3a increased the promoter activity of c-MYC and the transcription of the c-MYC gene. These results suggest that FOXO3a activates c-MYC expression, which, in turn,results in enhanced quantities of c-MYC at the hTERT promoter,enhanced transcriptional activation of c-MYC and, as a consequence, upregulati...

--

Human

L

delay aging

25,000,517

Gene

0

1

0

1

0

CCN1

3491

protein coding

--

Skin

Aging

Accelerate

Atomic force microscopy imaging

This increase of CCN1 was associated with constitutively reduced type I collagen, and constitutively elevated MMP-1 in forearm chronically sun-exposed prematurely aged human skin.

IL-1¦Â

Upregulation

qRT-PCR//ELISA

Elevated expression of CCN1 in dermal fibroblasts resulted in significant upregulation of IL-1¦ÂmRNA and protein levels.Importantly, knockdown of CCN1 induction significantly reduced UV irradiation induction of IL-1¦Â mRNA and protein levels, indicating that induction of IL-1¦Â is dependent, in part, on induction of CC...

--

Human

L

delay aging

23,881,607

Gene

0

1

0

TRIM28

10155

protein coding

IMR-90

--

Aging

Accelerate

BrdU assay//Crystal violet assay//Immunostaining//Knockdown//SAHF

We observed that TRIM28 depletion resulted in increased cell growth upon OIS induction,similar to what was observed upon p53 knockdown.TRIM28 knockdown also resulted in less cells presenting features characteristic of senescence such as senescence-associated heterochromatic foci.A higher percentage of cells with deplet...

p16

--

Immunostaining//knockdown

p16INK4a levels were lower upon knockdown of TRIM28.

--

Human

L

delay aging

25,160,591

Gene

0

1

0

1

0

1

0

1

0

1

0

ARG2

384

protein coding

HUVEC

--

Aging

Accelerate

SA--gal activity assay//Western blot

The senescence markers such as the number of SA-¦Â-gal positive cells,the levels of p53-S15 and p21Cip1 as well as levels of VCAM1 and ICAM1 are significantly augmented by Arg-II overexpression.

eNOS

--

Western blot//Immunostaining

Conversely, in nonsenescent cells, adenovirus-mediated ectopic expression of a wild-type (WT) Arg-II cDNA as verified by immunoblotting,leads to eNOS-uncoupling, i.e., impaired NO production (DAF-2DA staining) and enhanced intracellular O2-generation (DHE staining),which is significantly inhibited by the eNOS inhibitor...

--

Human

L

delay aging

22,928,666

Gene

0

1

0

1

0

RPS6KB1

6198

protein coding

HUVEC

--

Aging

Accelerate

SA--gal activity assay//Western blot

S6K1 increases the number of positively stained SA-¦Â-gal cells, elevates p53-S15 and p21Cip1 levels, and enhances VCAM1 and ICAM1 expression, demonstrating that persistent hyperActivate S6K1 promotes endothelial senescence and inflammation.

Arg-II

Upregulation

qRT-PCR

Indeed, in young endothelial cells, overexpression of a constitutively Activate S6K1 mutant (HA-S6K1ca), but not the inActivate S6K1 mutant, which is confirmed by immunoblotting with the anti-S6K1 antibody that detects both mutants, enhances Arg-II mRNA and protein levels paralleled with increased arginase activity.

--

Human

L

delay aging

22,928,666

Gene

0

1

0

1

0

JUND

3727

protein coding

Aortic endothelial cell

Aorta

Aging

Prevent

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

Telomerase activity was blunted in young JunD?/? compared with age-matched WT mouse aorta.This finding indicated a vascular senescence phenotype in young animals lacking JunD .¦Â-Galactosidase staining further supported the early occurrence of vascular aging in JunD?/? mice. Accordingly, the expression of aging markers...

p47phox//NOX2//NOX4

--//--//--

Immunostaining//Western blot

In contrast,the NADPH oxidase subunits p47phox, Nox2, and Nox4 were already upregulated in young JunD?/? mice and further increased with aging.

--

Human

L

delay aging

23,410,942

Gene

0

1

0

1

0

1

0

1

0

1

0

IGF1

3479

protein coding

MCF-7,IMR-90

--

Aging

Accelerate

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

IGF-1 treatment of IMR90 or MEF cells led to appearance of cells with feature characteristic of premature cellular senescence, including an enlarged flat cell morphology and increased ¦Â-Galactosidase (SA-¦Â-Gal) activity.By contrast, cells treated with IGF-1 remained morphologically large and flat, with marginal BrdU ...

--

SIRT1-p53

Activation

Western blot

IGF-1 significantly inhibited SIRT1 deacetylase activity.We confirmed comparable SIRT1 protein input levels by western blot analysis.IGF-1 treatment led to a marked increase in p53 protein levels in serum-starved MCF7, U2-OS, and IMR90 cells.IGF-1 treatment led to a substantial increase in p53 protein half-life, compar...

Human

L

delay aging

25,070,626

Gene

0

1

0

1

0

1

0

SIRT6

51548

protein coding

HCA2

--

Aging

Prevent

Immunostaining

SIRT6 reduced the number of ¦ÃH2AX foci.

PARP1

--

Western blot//Autoradiography

Instead, we used the specific PARP1 inhibitor PJ34. Importantly, PJ34 had no inhibitory effect on either deacetylation or mono-ADP ribosylation activities of SIRT6.In the presence of PJ34, SIRT6 overexpression had no effect on HR,indicating that SIRT6-mediated rescue of HR in aging cells is dependent on PARP1.

--

Human

L

delay aging

22,753,495

Gene

0

1

0

SIRT1

23411

protein coding

B-MSC,A-MSC

Bone and Adipose

Aging

Prevent

BrdU assay//Knockdown//PI staining//SA--gal activity assay

Compared to control, the knockdown of SIRT1 markedly slowed down the growth rate of both types of MSC, as shown by plotting a curve of the cell growth and by the use of a BrdU incorporation assay.In B-MSCs, SIRT1 knockdown significantly decreases the percentage of cells in S phase,while A-MSCs have significantly more c...

p16

--

Western blot

However, in late culture passages, p16 but not p21 is accumulated faster in B-MSCs where SIRT1 has been knocked down.Conversely, overexpression of SIRT1, but not its dominantnegative mutant H363Y , efficiently delayed the accumulation of p16.

--

Human

L

delay aging

22,038,097

Gene

0

1

0

1

0

1

0

1

0

PTEN

5728

protein coding

--

Human islet

Aging

Accelerate

Immunostaining//Knockdown

The percentage of Ki67 positive cells was dramatically increased in the Pten null mice that are 3 months old and older.

--

PI3K-Akt//cyclin D1-E2F-Ezh2-p16

Downregulation//--

Western blot

A primary biochemical function of PTEN is to inhibit the action of PI3K.We show that phosphorylation of the PI3K effector, serine/threonine kinase AKT, is dramatically induced in the Pten null islets compared with the Con ones, whereas the amount of p-ERK is minimally altered.Elevated cyclin D1 leads to the activation ...

Human

L

delay aging

23,826,727

Gene

0

1

0

1

0

RECQL4

9401

protein coding

Fibroblast

Mouse tail

Rothmund¨CThomson syndrome

Prevent

Immunostaining//SA--gal activity assay

Recql4HD fibroblasts expressed more SA-¦Â-gal than wild-type fibroblasts.In addition, the average number of 53BP1 foci was approximately threefold higher under 3%oxygen and fourfold higher under 20% oxygen in cells from old Recql4HDcells compared with cells from old wild-type cells. The average number of ¦ÃH2A.X foci p...

--

Human

HL

delay aging

24,832,598

Gene

0

1

0

1

0

E2F1

1869

protein coding

MEF

Embryo

Aging

Accelerate

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

The ability of MEFs to proliferate decreases with cell passage; knocking out E2F1 attenuates this effect. The proliferation of passage 5 WT MEFs was greatly reduced compared with E2F1 KO MEFs, with all cells visualized by Hoechst stained DNA but DNA synthesis was greatly reduced only in WT cells.by passage 5 a signific...

FOXO3

Downregulation

Luciferase reporter assay//Immunostaining

The reporters alone show some activation of the FKRE-luciferase gene, presumably from endogenous FOXO1/3 proteins. This activation is significantly repressed when the E2F1 plasmid is co-transfected.Moreover, the levels of intracellular ROS,as measured by dichlorofluorescein (DCF) levels, whether in the steady state or ...

--

Human

L

delay aging

25,344,604

Gene

0

1

0

1

0

1

0

E2

1489080

protein coding

HeLa

--

Aging

Accelerate

Cell morphological analysis//SA--gal activity assay

The parental HeLa cells infected with the E2 virus expressed the expected senescent phenotype including growth arrest, increased cell size and flattening, elevated autofluorescence and high level SA-¦Â-gal activity.

--

Human

HL

delay aging

16,626,397

Gene

0

1

0

1

0

IGF1

3479

protein coding

Myocyte

--

Cardiomyopathy and heart failure

Prevent

Telomere length assay//Western blot

IGF-1 interfered with the age-dependent increases in myocyte size, telomeric shortening and p16INK4aand p53 proteins.

--

PI3K-Akt

Activation

Western blot

Akt protein (total) remained constant and did not differ in WT and TG myocytes. However, phospho-Akt levels decreased in WT and increased in TG myocytes from 4 to 20 to 22 months.

Human

L

delay aging

14,726,476

Gene

0

1

0

1

0

UBE2I

7329

protein coding

U2OS

--

Aging

Prevent

Growth curve assay

Under senescence promoting conditions there is a clear delay for the onset ofsenescence in U2OS when cells express the wild type form of UBC9 while the K49R variant shows no effect and undergoes senescence like the control cells.

PML

Binding

Growth curve assay

As expected, both Ubc9-PML and Ubc9K49R-PML fusion proteins localized to nuclear bodies.Expressing either Ubc9-PML or Ubc9K49R-PML fusion proteins counteracted the senescence induced by PML as compared to GFP-PML fusion in control cells .

--

Human

L

delay aging

29,773,808

Gene

0

1

0

HGF

3082

protein coding

hE-MSC,BM-MSC

--

Liver disease

Prevent

FISH//qRT-PCR

RTL was analyzed after treating hE-MSCs with a neutralizing HGF antibody.Telomere length was decreased to 50% and PDT was delayed to 80 hr upon loss of HGF function in hE-MSCs.Interphase telomere fluorescence in situ hybridization (FISH) showed that treatment of hBM-MSCs with rHGF increased the number and intensity of ...

RAD51

Upregulation

HR assay//Western blot

When we treated hBM-MSCs with rHGF, the activity and protein level of RAD51 increased.When we blocked HGF in hE-MSCs using a neutralizing antibody,the protein level of RAD51 decreased.

--

Human

L

delay aging

29,398,486

Gene

0

1

0

1

0

MCL1

4170

protein coding

HCT116

--

Colorectal cancer

Prevent

Immunostaining

Impressively, DPI (similar to NAC) caused a robust abrogation of ROS generation in Mcl-1 deficient cells as compared with the Mcl-1 proficient cells during CIS conditions after 24 hours of culture with doxorubicin, a time point that significant differences in ROS production can be observed.

NOX4

Downregulation

Western blot//Co-IP

Immunoblot analysis using NOX4 specific antibody shows that NOX4 is predominantly up regulated in the mitochondrial fraction in CIS-sensitive cells under doxorubicin treatment in the absence of Mcl-1.Mcl-1 has a unique ability to inhibit ROS production by preventing the up regulation of the pro-oxidant NOX4.

--

Human

L

delay aging

28,423,654

Gene

0

1

0

MAPK1

5594

protein coding

Fibroblast

--

Prostate cancer

Accelerate

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

ERK2 knockdown in cells expressing RasV12 inhibited the induction of senescence-associated ¦Â-galactosidase (SA-¦Â-Gal), PML bodies, and DNA damage foci.Oncogenic ras engaged the p53/p21, p16INK4a/RB, and p38MAPK pathways in primary cells, and this was efficiently prevented by knockdown of ERK2.The induction of several...

--

Human

HL

delay aging

23,599,344

Gene

0

1

0

1

0

1

0

SOD2

6648

protein coding

Chondrocyte

Bone

Cartilage degeneration

Prevent

Flow cytometry//Safranin O/Fast Green staining

Histological analyses by the OARSI score revealed that Sod2 cKO joints exhibited a significant loss of safranin-O staining in all layers of both articular cartilages in Sod2 cKO mice.The control joint showed the loss of safranin-O staining without morphological changes in the superficial layer of MFC and MTP .Sod2 cKO ...

--

Human

L

delay aging

26,108,578

Gene

0

1

0

1

0

LMNA

4000

protein coding

--

Embryo

Aging

Prevent

SA--gal activity assay

The zLMNA-MO2 morphants showed a high intensity of SA-¦Â-gal at 6 dpf, whereas zLMNA-MO1 morphants did not show significantly detectable SA-¦Â-gal activity.

--

Human

L

delay aging

21,479,207

Gene

0

1

0

SOD3

6649

protein coding

Fibroblast

Skin

Aging

Prevent

Survival curve

SOD3R213G Tg mice exhibited a shortened life span with their hair turning gray upon aging.

--

Human

HL

delay aging

25,927,599

Gene

0

1

0

DKC1

1736

protein coding

MEF

Embryo

X-linked dyskeratosis congenita

Prevent

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

In 3% oxygen, ¡÷15 cells grew more slowly and entered senescence earlier than WT cells.¡÷15 cells accumulated more ROS than WT cells and the difference became very significant with more PDs, even when cell .There was a significantly higher number of foci in D15 cells, and the difference was greater in high oxygen.

--

Human

L

delay aging

21,241,452

Gene

0

1

0

1

0

1

0

IRS2

8660

protein coding

Astrocyte

Brain

Huntington disease

Accelerate

Survival curve

The body weights of R6/2?Irs2ntg mice increased normally until 7 weeks, but afterward declined rapidly, and half the mice died between 11 and 12 weeks of age. Based on Cox regression,neuronal Irs2 in R6/2?Irs2ntg mice significantly increased the risk of death 3.6-fold compared with R6/2 mice;sex of the mice was not a s...

FOXO1

--

Western blot

The fractionation of brain homogenates and immunoblotting confirmed that phosphorylated FoxO1 was largely cytoplasmic in R6/2 and R6/2?Irs2ntg mice, whereas FoxO1 was weakly phosphorylated and most strongly detected in the nuclear (laminin-containing) fractions from R6/2?Irs2+/¨C?Irs2¦Âtg brains.

--

Human

L

delay aging

21,926,467

Gene

0

1

0

TP53

7157

protein coding

MEF

--

Tumor

Accelerate

Cell morphological analysis//SA--gal activity assay

The shorter survival of nontumor-bearing p53S18Amice suggests that their aging process could be accelerated due to the Ser18mutation. In fact, these mice exhibited heightened expression of several factors associated with aging, such as inability to heal, premature graying, chronic alopecia, and lordokyphosis. The numbe...

--

Human

L

delay aging

18,089,799

Gene

0

1

0

1

0

ING1

3621

protein coding

Hs68

--

Aging

Accelerate

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

The occurrence of SAHF in senescent cell nuclei (panel B) and highlights the similarity of nuclear phenotype and DNA staining patterns between senescent cells and cells expressing high levels of INGla.Examining the effect of ING1a on cell cycle distribution showed that overexpression of INGla induced cell cycle arrest ...

--

p16-pRb

Activation

Western blot

ING1a expression substantially increased both pl6 and pRb levels.

Human

L

apoptosis

18,691,180

Gene

0

1

0

1

0

1

0

PTEN

5728

protein coding

BM-MSC

--

Systemic Lupus Erythematosus

Accelerate

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

There were less SA-¦Â-gal-positive cells when PTEN expression was knocked down in BM-MSCs from SLE patients, but it has less effect in the control group¡¯s BM-MSCs. The further quantitative analysis indicated the number of SLE patients¡¯ BM-MSCs increased in si-PTEN-transfected group compared to the untreated group fr...

--

p27

Upregulation

Western blot//Immunofluorescence

In the BM-MSCs from SLE patients, we found that the expression of PTEN was up-regulated, and the phosphorylation of Akt was reduced. Meanwhile, the higher expression of PTEN and the lower expression of p-Akt in SLE BM-MSCs were confirmed by immunofluorescence. The expression of cell-cycle regulator p27kip1 was determin...

Human

L

apoptosis

25,649,549

Gene

0

1

0

1

0

1

0

BTK

695

protein coding

EJp53,HDF

--

Aging

Accelerate

Growth curve assay//SA--gal activity assay

Inhibition of BTK by chemical or genetic approaches increased cell proliferation in EJp53 induced to senesce. Indeed, the percentage of cells positive for senescence associated (SA)-¦Â-gal, a widely used marker of senescence (32), was significantly lower when BTK was inhibited, and less cells showed the morphological c...

--

p53

Activation

Western blot//RT-PCR

We found that BTK protein levels were elevated after inducing p53 expression in these cells. Moreover, the colon cancer cell line HCT116, which has wild-type p53, also showed a p53-dependent BTK induction after being treated with DNA damaging agents (the oxidant tBH and doxorubicin), both at protein and mRNA levels. We...

Human

L

apoptosis

27,630,139

Gene

0

1

0

1

0

KRT24

192666

protein coding

Primary human epidermal keratinocyte

Skin

Aging

Accelerate

EdU Assay//Flow cytometry//MTS assay//SA--gal activity assay

The results indicated that K24 overexpressed keratinocytes showed decreased proliferation rate, as compared with control cells. Furthermore, the actual proliferative capacity of the K24 overexpressed keratinocytes was then determined by EdU assay. The percentage of proliferating cells from the K24 overexpressed cells w...

--

Human

L

apoptosis

28,362,807

Gene

0

1

0

1

0

1

0

1

0

DLK1

8788

protein coding

WI-38

--

Aging

Prevent

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

Cells infected with the Sh-hDLK2 lentiviral construct exhibited a significantly slower rate of proliferation when compared to control cells,suggesting that depletion of DLK inhibited cell proliferation.Our results showed that loss of DLK results in a diminution of cells in S phase, an increased proportion (¡«20%) of ce...

--

ERK//p53-p21

--//--

Western blot//Knockdown

In DLK-depleted cells, we noted a substantial decrease in ERK phosphorylation level relative to control , indicating that ERK activity in WI-38 cells is dependent on DLK. we observed that p53 and p21 expression was significantly up-regulated in DLK-depleted cells as compared to cells infected with the control lentiviru...

Human

L

apoptosis

21,893,036

Gene

0

1

0

1

0

1

0

SAE2

816686

protein coding

HCT116,U2OS

--

Cancer

Prevent

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

SAE2 and UBC9 shRNAs (sh1 and sh2) potently blocked colony formation in vitro.By PI staining and flow cytometry, we observed increased sub-G1 cell population in HCT116 cells upon conditional SAE2 knockdown , suggesting some cells are undergoing apoptosis.By BrdU incorporation assay, we observed a decreased percentage o...

--

SUMO

Activation

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

As further confirmation that the non-silencible SAE2 can functionally rescue the SUMO pathway activity, we performed the same sub-G1 apoptosis assay and SA-¦Â-Gal staining. The wildtype SAE2, but not the C->A enzyme dead SAE2 mutant, partially rescued shSAE2 induced multinucleation and senescence,and associated cell de...

Human

L

apoptosis

25,860,128

Gene

0

1

0

1

0

1

0

1

0

1

0

IFNG

3458

protein coding

Melanocyte

--

Vitiligo

Accelerate

Flow cytometry//SA--gal activity assay

IFN-¦Ã significantly decreased the cell viability in a dose dependent manner. Cell cycle analysis results demonstrated that IFN-c at both concentrations caused the accumulation of melanocytes at G1 phase, while decreased the percentage of cells at S and G2/M phases.In contrast, melanocytes after persistent IFN-¦Ã treat...

p21/WAF1

Upregulation

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

Immunoblotting analysis indicated that protein level of p21 was greatly elevated with the increasing duration of IFN-¦Ã treatment,while p16 level didn¡¯t change during the experiment.P21 siRNA treatment suppressed the IFN-¦Ã-induced increase of SA-¦Â-gal staining.

JAK2-STAT1

--

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

In the presence of IFN-¦Ã, the cell viability of control siRNA transfected melanocytes was significantly inhibited. Significantly, JAK2 or STAT1 siRNA efficiently restored the viability of melanocytes. Immunoblotting results confirmed that JAK2 or STAT1 siRNA, but not JAK1 siRNA inhibited the increase of p21 induced by...

Human

L

apoptosis

24,681,574

Gene

0

1

0

1

0

CTSK

1513

protein coding

MEF,NHDF

--

Aging

Prevent

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

NHDF lacking cathepsin X exhibited a flattened cell body and a significant increase in size in comparison to control cells expressing normal amounts of cathepsin X. Quantification of SA-¦Â-gal in NHDF lacking cathepsin X clearly demonstrated a significant increase both in the number of stained cells and in the intensit...

--

Human

L

apoptosis

21,616,554

Gene

0

1

0

1

0

1

0

MDM2

4193

protein coding

H460

--

Lung cancer

Prevent

Flow cytometry//SA--gal activity assay

Missense oligonucleotide alone caused apoptosis in 5.6 ¡À 0.6% (mean F SD) cells and radiation treatment increased this to 16 ¡À 1.3%. The anti-MDM2 oligonucleotide alone had a greater effect than the missense oligonucleotide with 18 ¡À 0.2% apoptotic cells.Missense oligonucleotide caused 2.7¡À0.2% and 7.0 ¡À 0.6% (mea...

p53//p21

Upregulation//Upregulation

Western blot

H460 cells pretreated with missense ASODN followed by 5 Gy showed an increase in MDM2,p53, and p21 expression at 24 hours, compared with H460 treated with missense ASODN alone.

--

Human

L

apoptosis

16,093,429

Gene

0

1

0

1

0

CDKN1C

1028

protein coding

HepG2,SNU398 HCC

--

Hepatocellular carcinoma

Accelerate

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

Induction of P57 reduced proliferation of HepG2 and SNU398 HCC cells, as demonstrated by growth curve analysis.FACS analysis revealed that P57 transfected cells accumulate in G1 phase of cell cycle. Seventy-two hours post-P57 transfection, cells began to change the morphology, becoming enlarged and flattened, and they ...

--

Hes1

--

RT-PCR//Western blot

Notch3-and Notch1-silenced cells showed a down-regulation of Hes1 target gene together with an up regulation of P57 mRNA and protein levels .Down-regulation of Hes1 significantly increased P57 mRNA and protein levels in both analyzed cell lines .In HepG2 cells, but not in HepG2, with siRNA to Hes1, DNA of the P57 promo...

Human

L

apoptosis

22,705,236

Gene

0

1

0

1

0

1

0

1

0