Resveratrol Induced Premature Senescence Is Associated with DNA Damage Mediated SIRT1 and SIRT2 Down-Regulation

Eren, Mehtap Kilic; Kılınçlı, Ayten; Eren, Özkan

doi:10.1371/journal.pone.0124837

Cited by 55 publications

(35 citation statements)

References 42 publications

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“…28 However, a recent report indicated that increase in SIRT2 levels in aged rat brain is specific only to occipital region and no other regions. 36 In contrast to the results of our study, a recent report by Kilic Eren et al, (2015) 37 showed decrease in SIRT2 levels in resveratrol induced premature senescence in human fibroblasts. Thus, the reports are contradictory and in general the published reports till now point toward role of SIRT2 loss or overexpression as a cause for senescence induction.…”

Section: Discussioncontrasting

confidence: 99%

Increased expression of SIRT2 is a novel marker of cellular senescence and is dependent on wild type p53 status

2016

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Sirtuins (SIRT) belonging to the NADC dependent histone deacetylase III class of enzymes have emerged as master regulators of metabolism and longevity. However, their role in prevention of organismal aging and cellular senescence still remains controversial. In the present study, we now report upregulation of SIRT2 as a specific feature associated with stress induced premature senescence but not with either quiescence or cell death. Additionally, increase in SIRT2 expression was noted in different types of senescent conditions such as replicative and oncogene induced senescence using multiple cell lines. Induction of SIRT2 expression during senescence was dependent on p53 status as depletion of p53 by shRNA prevented its accumulation. Chromatin immunoprecipitation revealed the presence of p53 binding sites on the SIRT2 promoter suggesting its regulation by p53, which was also corroborated by the SEAP reporter assay. Overexpression or knockdown of SIRT2 had no effect on stress induced premature senescence, thereby indicating that SIRT2 increase is not a cause of senescence; rather it is an effect linked to senescence-associated changes. Overall, our results suggest SIRT2 as a promising marker of cellular senescence at least in cells with wild type p53 status.

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Section: Discussioncontrasting

confidence: 99%

Increased expression of SIRT2 is a novel marker of cellular senescence and is dependent on wild type p53 status

2016

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“…The effects of RES on cellular senescence have been widely investigated, although the results are contradictory. Multiple studies, including our own, have pointed out that RES can attenuate cell ageing; other have demonstrated that it can actually induce senescent phenotype, but in cancer cell lines . However, the molecular mechanisms responsible for that activity were not fully elucidated.…”

Section: Discussionmentioning

confidence: 95%

5‐Azacytydine and resveratrol reverse senescence and ageing of adipose stem cells via modulation of mitochondrial dynamics and autophagy

Kornicka

Szłapka-Kosarzewska

Śmieszek

et al. 2018

J Cellular Molecular Medi

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Obesity and endocrine disorders have become prevalent issues in the field of both human and veterinary medicine. Equine metabolic syndrome is a complex disorder involving alternation in metabolism and chronic systemic inflammation. It has been shown that unfavourable microenvironment of inflamed adipose tissue negatively affects adipose stem cell population (ASC) residing within, markedly limiting their therapeutic potential. ASCsEMS are characterized by increased senescence apoptosis, excessive accumulation of reactive oxygen species (ROS), mitochondria deterioration and “autophagic flux.” The aim of the present study was to evaluate whether treatment of ASCsEMS with a combination of 5‐azacytydine (AZA) and resveratrol (RES) would reverse aged phenotype of these cells. For this reason, we performed the following analyzes: molecular biology (RT‐PCR), microscopic (immunofluorescence, TEM) and flow cytometry (JC‐1, ROS, Ki67). We evaluated the mitochondrial status, dynamics and clearance as well as autophagic pathways. Furthermore, we investigated epigenetic alternations in treated cells by measuring the expression of TET genes and analysis of DNA methylation status. We have demonstrated that AZA/RES treatment of ASCsEMS is able to rejuvenate these cells by modulating mitochondrial dynamics, in particular by promoting mitochondrial fusion over fission. After AZA/RES treatment, ASCsEMS were characterized by increased proliferation rate, decreased apoptosis and senescence and lower ROS accumulation. Our findings offer a novel approach and potential targets for the beneficial effects of AZA/RES in ameliorating stem cell dysfunctions.

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“…RV was also found to induce premature senescence via decreasing SIRT1 and SIRT2 levels in human dermal fibroblasts. The decline in SIRT1/2 expression in response to RV treatment showed that DNA damage was regulated by RV (38). Kao et al (39) reported that RV treatment reduced oxidative stress in human endothelial cells via induction of SIRT1 activation in endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Protects Sepsis-Induced Oxidative DNA Damage in Liver and Kidney of Rats

Aydın¹,

Şahin²,

Bacanlı³

et al. 2016

Balkan Med J

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Background:The increases of free radicals have been proposed to be involved in the pathogenesis of sepsis, which leads to multiple-organ dysfunction syndromes. The uses of antioxidants as a complementary tool in the medical care of oxidative stress-related diseases have attracted attention of researchers. Resveratrol (RV) has suggested being antioxidant, anti-proliferative, and anti-inflammatory effects in various experimental models and clinical settings. Aims: This study was undertaken to evaluate the protective effects of RV on oxidative DNA damage induced by sepsis in the liver and kidney tissues of Wistar albino rats. Study Design: Animal experimentation. Methods: Four experimental groups consisting of eight animals for each was created using a total of thirty-two male Wistar albino rats. Sham group was given 0.5 mL of saline intra-peritoneal (ip) only following laparatomy. Sepsis group was given 0.5 mL saline ip only following the induction of sepsis. RV-treated group was given a dose of 100 mg/kg ip RV in 0.5 mL saline following laparatomy. RVtreated sepsis group was given 100 mg/kg ip RV in 0.5 mL saline following the induction of sepsis. A model of sepsis was created by cecal ligation and puncture technique. In the liver and kidney tissues, oxidative stress parameters (malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPX)) and a proinflammatory cytokine (tumor necrosis factor alpha (TNF-alpha)), were evaluated spectrophotometrically and DNA damage was determined by the alkaline single cell gel electrophoresis (comet assay) technique using formamidopyrimidine DNA glycosylase protein. Results:In the RV-treated sepsis group, the levels of MDA and TNF-alpha were lower and GSH levels, SOD and GPX activities were higher than in the septic rats (p<0.05). RV treatment significantly reduced the sepsis-induced oxidative DNA damage in the liver and kidney cells (p<0.05). Conclusion: It is suggested that RV treatment might reduce the sepsis-induced oxidative DNA damages in sepsis-related diseases; however, there is a need for more studies to clear up the protective mechanisms of RV against sepsis.

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Resveratrol Induced Premature Senescence Is Associated with DNA Damage Mediated SIRT1 and SIRT2 Down-Regulation

Cited by 55 publications

References 42 publications

Increased expression of SIRT2 is a novel marker of cellular senescence and is dependent on wild type p53 status

Increased expression of SIRT2 is a novel marker of cellular senescence and is dependent on wild type p53 status

5‐Azacytydine and resveratrol reverse senescence and ageing of adipose stem cells via modulation of mitochondrial dynamics and autophagy

Resveratrol Protects Sepsis-Induced Oxidative DNA Damage in Liver and Kidney of Rats

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