SirT3 and p53 Deacetylation in Aging and Cancer

Chen, Ji‐Jun; Wang, Aiqin; Chen, Qingqi

doi:10.1002/jcp.25669

Cited by 50 publications

(26 citation statements)

References 60 publications

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“…Only 78 genes that are highly expressed in lung are further screened out by Gene (gene-centered information at NCBI) from the 128 genes. Then, 25 differential expression genes were selected as the aging-related genes profile, which, based on previous literatures, were less studied in COPD or considered to be classical ageing-related gene [27–32]. In addition, based on the 4 selected COPD-related databases, meta-analysis of the candidate 25 aging-related genes showed that 9 genes (FOXO3, TP53, TGFβ1, MMP2, HDAC1, NUF2, ATG3, AREG and E2F1) were significantly altered in the COPD group compared to the control group (Table 2 and Additional file 3).…”

Section: Resultsmentioning

confidence: 99%

Variable DNA methylation of aging-related genes is associated with male COPD

Du¹,

Lin²,

Wu³

et al. 2019

Respir Res

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BackgroundChronic obstructive pulmonary disease (COPD) is a chronic lung inflammatory disease which has a close relationship with aging. Genome-wide analysis reveals that DNA methylation markers vary obviously with age. DNA methylation variations in peripheral blood have the potential to be biomarkers for COPD. However, the specific DNA methylation of aging-related genes in the peripheral blood of COPD patients remains largely unknown.MethodsFirstly, 9 aging-related differentially expressed genes (DEGs) in COPD patients were screened out from the 25 aging-related genes profile through a comprehensive screening strategy. Secondly, qPCR and multiple targeted bisulfite enrichment sequencing (MethTarget) were used to detect the mRNA level and DNA methylation level of the 9 differentially expressed genes in the peripheral blood of 60 control subjects and 45 COPD patients. The candidate functional CpG sites were selected on the basis of the regulation ability of the target gene expression. Thirdly, the correlation was evaluated between the DNA methylation level of the key CpG sites and the clinical parameters of COPD patients, including forced expiratory volume in one second (FEV1), forced expiratory volume in one second as percentage of predicted volume (FEV1%), forced expiratory volume/ forced vital capacity (FEV/FVC), modified British medical research council (mMRC) score, acute exacerbation frequency and the situation of frequent of acute aggravation (CAT) score. Lastly, differentially methylated CpG sites unrelated to smoking were also determined in COPD patients.ResultsOf the 9 differentially expressed aging-related genes, the mRNA expression of 8 genes were detected to be significantly down-regulated in COPD group, compared with control group. Meanwhile, the methylated level of all aging-related genes was changed in COPD group containing 219 COPD-related CpG sites in total. Notably, 27 CpG sites of FOXO3 gene showed a lower False Discovery Rate (FDR) and higher methylation difference values. Also, some variable DNA methylation is associated with the severity of COPD. Additionally, of the 219 COPD-related CpG sites, 147 CpG sites were not related to smoking.ConclusionThese results identified that the mRNA expression and DNA methylation level of aging-related genes were changed in male COPD patients, which provides a molecular link between aging and COPD. The identified CpG markers are associated with the severity of COPD and provide new insights into the prediction and identification of COPD.

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Section: Resultsmentioning

confidence: 99%

Variable DNA methylation of aging-related genes is associated with male COPD

Du¹,

Lin²,

Wu³

et al. 2019

Respir Res

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“…Similarly, the levels of SIRT3, a mitochondrial deacetylase, were decreased in high glucose-induced senescent cells [47] and in the aged brain of mice [48]. Reduced levels of SIRT3 lead to increased ROS production and subsequent aging via increase in activated p53 level [49]. In addition, SIRT3 has a pro-proliferative function in human melanoma cells [50].…”

Section: Discussionmentioning

confidence: 99%

Nectandrin B-mediated activation of the AMPK pathway prevents cellular senescence in human diploid fibroblasts by reducing intracellular ROS levels

Jang

Yang

et al. 2019

Aging

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Nectandrin B (NecB) is a bioactive lignan compound isolated from Myristica fragrans (nutmeg), which functions as an activator of AMP-activated protein kinase (AMPK). Because we recently found that treatment with NecB increased the cell viability of old human diploid fibroblasts (HDFs), the underlying molecular mechanism was investigated. NecB treatment in old HDFs reduced the activity staining of senescence-associated β-galactosidase and the levels of senescence markers, such as the Ser 15 phosphorylated p53, caveolin-1, p21 waf1 , p16 ink4a , p27 kip1 , and cyclin D1. NecB treatment increased that in S phase, indicating a enhancement of cell cycle entry. Interestingly, NecB treatment ameliorated age-dependent activation of AMPK in old HDFs. Moreover, NecB reversed the age-dependent expression and/or activity changes of certain sirtuins (SIRT1−5), and cell survival/death-related proteins. The transcriptional activity of Yin-Yang 1 and the expression of downstream proteins were elevated in NecB-treated old HDFs. In addition, NecB treatment exerted a radical scavenging effect in vitro , reduced cellular ROS levels, and increased antioxidant enzymes in old HDFs. Moreover, NecB-mediated activation of the AMPK pathway reduced intracellular ROS levels. These results suggest that NecB-induced protection against cellular senescence is mediated by ROS-scavenging through activation of AMPK. NecB might be useful in ameliorating age-related diseases and extending human lifespan.

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“…SIRT3 is also reported to be a nuclear NAD + ‐dependent histone deacetylase targeting histone 3 lysine 9 (H3K9) and histone 4 lysine 16 (H4K16) during cellular stress conditions . SIRT3 regulates a wide range of important biological functions including metabolic control, neuroprotection, cardiovascular diseases, aging, and cancer, mainly through its deacetylase activity. However, its role in HBV replication remains unexplored.…”

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confidence: 99%