| External factors: | Trimethylamine-N-oxide |
| Aging type: | Accelerate |
| Aging characteristic: |
| Category: | Chemical compounds |
| Phenotype: | Cardiovascular disease |
| Experiment: | SA-β-gal activity assay//Western blot//Cell viability assay//Flow cytometry//Wound healing assay |
| Description: | After TMAO treatment, the SA-β-gal activity was slightly increased in the SAMR1 group and further elevated in the SAMP8 mice.HUVECs treated with 200 mM and 500 mM TMAO showed a decrease in the cell proliferation rates in a time-dependent manner.Then, SA-β-gal staining and western blot analyses were performed.Gradual increases in the percentage of SA-β-gal positive cells and the slight upregulation of p53, p21, and plasminogen activator inhibitor-1 (PAI-1) were observed in TMAO-treated HUVECs.TMAO treatment resulted in G0/G1 cell cycle arrest. Moreover, TMAO treatment decreased cell migration in HUVECs measured using a wound-healing assay. |
| Target gene: | SIRT1 |
| R-EF-Target gene: | Downregulation |
| Official symbol(s): | SIRT1 |
| Target gene experiment: | Western blot//RT-PCR |
| Target gene description: | The NO concentration and the expression of eNOS and SIRT1 decreased in SAMP8 mice compared with SAMR1 mice. |
| Regulatory pathway: | p53-p21-Rb |
| R-EF-Pathway: | Activation |
| Official symbol(s): | TP53-CDKN1A |
| Pathway experiment: | Western blot//qRT-PCR |
| Pathway description: | TMAO treatment could increase the expression of p53 and p21, induce acetylation of p53, decrease the expression of CDK2 and cyclinE1, and reduce the phosphorylation of Rb. Quantitative PCR analysis showed comparable results. |
Annotation: