Senescence Abstracts 2

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Vitamin C inhibits p53-induced replicative senescence through suppression of ROS production and p38 MAPK activity.
            (Kim et al., 2008) Download
We previously reported that tumor cells expressing p53 increase intracellular levels of reactive oxygen species (ROS). In this study, we described an inhibitory effect of vitamin C on replicative senescence. Vitamin C was found to inhibit p53-induced senescence in human bladder cancer EJ cells. The senescence-like phenotype (SLP) induced by p53, which showed a morphological change and an irreversible cell cycle arrest, was not observed in vitamin C-treated EJ cells. In addition, vitamin C did not significantly affect normal cell proliferation. We investigated the molecular mechanisms of the inhibitory effect of vitamin C on the development of replicative senescence in EJ cells. We found that vitamin C inhibited this p53-induced ROS generation. Moreover, p38 kinase which was activated during p53-induced senescence was not observed in vitamin C-treated EJ cells. SB203580, a chemical inhibitor of p38 kinase, was found to consistently inhibit p53-induced senescence. Therefore, it is suggested that vitamin C inhibits p53-induced senescence by preventing ROS generation, which in turn leads to the activation of p38 MAPKinase. These results reveal the inhibitory mechanism of vitamin C on cellular senescence.

Salidroside protects against premature senescence induced by ultraviolet B irradiation in human dermal fibroblasts.
            (Mao et al., 2015) Download
OBJECTIVES:  Salidroside, the predominant component of a Chinese herbal medicine, Rhodiola rosea L., becomes an attractive bio-agent due to its multifunction. Although it is well proposed that this herbal medicine may have photoprotective effect according to the folk hearsay, the direct supportive experimental evidences linking the drug with skin ageing have rarely been reported so far. The study was conducted to investigate the photoprotective role of salidrosdie and its related mechanisms in vitro. METHODS:  First, a premature senescence model induced by UVB irradiation (250 mJ cm(-2)) in human dermal fibroblasts (HDFs) was established, and senescent phenotypes were evaluated by cell morphology, cell proliferation, senescence-associated beta-galactosidase (SA-β-gal) activity and cell cycle distribution. Then the photoprotective effect of salidroside was investigated. Cells were pre-treated with various doses of salidroside (1, 5 and 10 μM) followed by the sublethal dosage of UVB exposure and then were harvested for various detections, including senescence-associated phenotypes and molecules, alteration of oxidative stress, matrix metalloproteinase-1 (MMP-1) secretion and inflammatory response. RESULTS:  Pre-treatment of salidroside dose dependently reversed the senescent state of HDFs induced by UVB as evidenced by elevated cell viability, decreased SA-β-gal activity and relieving of G1/G0 cell cycle arrest. UVB-induced increased protein expression of cyclin-dependent kinase (CDK) inhibitors p21(WAF) (1) and p16(INK) (4) was also repressed by salidrosdie treatment in a dose-dependent manner. Meanwhile, the increment of malondialdehyde (MDA) level in UVB-irradiated HDFs was inhibited upon salidroside treatment. Additionally, salidroside significantly attenuated UVB-induced synthesis of MMP-1 as well as the production of IL-6 and TNF-α in HDFs. CONCLUSION:  Our data provided the evidences for the protective role of salidroside against UVB-induced premature senescence in HDFs probably via its anti-oxidative property and inhibition on production of MMP-1 and pro-inflammatory cytokines, which indicated its potential utilization as an active ingredient in the preparation of photoprotective formulation.

Vitamin D protects endothelial cells from irradiation-induced senescence and apoptosis by modulating MAPK/SirT1 axis.
            (Marampon et al., 2015) Download
PURPOSE:  Radiotherapy toxicity is related to oxidative stress-mediated endothelial dysfunction. Here, we investigated on radioprotective properties of Vitamin D (Vit.D) on human endothelial cells (HUVEC). METHODS:  HUVEC, pre-treated with Vit.D, were exposed to ionizing radiation (IR): ROS production, cellular viability, apoptosis, senescence and western blot for protein detection were performed. The role of MAPKs pathway was investigated by using U0126 (10 μM) MEKs/ERKs-, SB203580 (2.5 μM) p38-inhibitor or by over/expressing MKK6 p38-upstream activator. RESULTS:  Vit.D reduced IR-induced ROS production protecting proliferating and quiescent HUVEC from cellular apoptosis or senescence, respectively, by regulating MAPKs pathways. In proliferating HUVEC, Vit.D prevented IR-induced apoptosis by activating ERKs while in quiescent HUVEC counteracted IR-induced senescence by inhibiting the p38-IR-induced activation. MEKs&ERKs inhibition in proliferating or MKK6/mediated p38 activation in quiescent HUVEC, respectively, reverted anti-apoptotic or anti-senescent Vit.D properties. SirT1 protein expression levels were up-regulated by Vit.D. ERKs inhibition blocked Vit.D-induced SirT1 protein up-regulation in proliferating cells. In quiescent HUVEC cells, p38 inhibition counteracted the IR-induced SirT1 protein down-regulation, while MKK6 transfection abrogated the Vit.D positive effects on SirT1 protein levels after irradiation. SirT1 inhibition by sirtinol blocked the Vit.D radioprotective effects. CONCLUSION:  Vit.D protects HUVEC from IR induced/oxidative stress by positively regulating the MAPKs/SirT1 axis.

Adrenal Atrophy And Senescence Produced By A Vitamin Deficiency.
            (Morgan and Simms, 1939) Download
In the course of experiments with young rats on the symptoms produced by the deficiency of B2 complex, the fur of black and brown rats turned grey, course and lifeless. The changes can be cured by injection of relatively large doses of adrenal cortical extract, and not by B1, B6, riboflavin, copper or iron, or nicotinic acid or epinephrine.

Free D-amino acids in human plasma in relation to senescence and renal diseases.
            (Nagata et al., 1987) Download
Minute but appreciable amounts of D-amino acids were detected in normal human plasma. The content was significantly higher in an elderly population (age 76 +/- 6 years, mean +/- SD, n = 41) than in a younger group (age 42 +/- 4 years, n = 26), i.e. 6.9 +/- 4.8 nmol/ml (mean +/- SD, range 0-18.8 nmol/ml) and 2.5 +/- 1.8 nmol/ml (range 0-6.3 nmol/ml) for the elderly and the younger groups, respectively. Elevation of plasma D-amino acid level was observed in a group of patients with renal disease (3.6-52.6 nmol/ml), in proportion to the serum level of creatinine (n = 50, r = 0.726, P less than 0.001), beta 2-microglobulin (n = 34, r = 0.551, P less than 0.005), and to glomerular filtration rate (n = 39, r = 0.556, P less than 0.001).

Ginsenoside Rg1 enhances endothelial progenitor cell angiogenic potency and prevents senescence in vitro.
            (Shi et al., 2011) Download
This study investigated the effect of ginsenoside Rg1 on the functions of ex vivo cultivated endothelial progenitor cells (EPCs) and whether ginsenoside Rg1 prevented EPC senescence. EPCs isolated from peripheral blood from healthy volunteers were incubated with different concentrations of ginsenoside Rg1 and the effects were observed at different time points. Cell proliferation and in vitro vasculogenesis were assayed and flow cytometry was used to determine the effects of ginsenoside Rg1 on the cell cycle. Senescence and telomerase activity in EPCs were also assayed. It was found that ginsenoside Rg1 promoted EPC proliferation and vasculogenesis in dose-and time-dependent manners. Cell-cycle analysis showed that ginsenoside Rg1 increased the proliferative phase and decreased the resting phase of EPCs. β-Galactosidase and telomerase activities increased. These results support the view that ginsenoside Rg1 induces EPC proliferation and angiogenesis, and inhibits EPC senescence.


References

Kim, JE, et al. (2008), ‘Vitamin C inhibits p53-induced replicative senescence through suppression of ROS production and p38 MAPK activity.’, Int J Mol Med, 22 (5), 651-55. PubMedID: 18949386
Mao, GX, et al. (2015), ‘Salidroside protects against premature senescence induced by ultraviolet B irradiation in human dermal fibroblasts.’, Int J Cosmet Sci, 37 (3), 321-28. PubMedID: 25639473
Marampon, F, et al. (2015), ‘Vitamin D protects endothelial cells from irradiation-induced senescence and apoptosis by modulating MAPK/SirT1 axis.’, J Endocrinol Invest, PubMedID: 26335302
Morgan, AF and HD Simms (1939), ‘Adrenal Atrophy And Senescence Produced By A Vitamin Deficiency.’, Science, 89 (2320), 565-66. PubMedID: 17741477
Nagata, Y, et al. (1987), ‘Free D-amino acids in human plasma in relation to senescence and renal diseases.’, Clin Sci (Lond), 73 (1), 105-8. PubMedID: 3301163
Shi, AW, et al. (2011), ‘Ginsenoside Rg1 enhances endothelial progenitor cell angiogenic potency and prevents senescence in vitro.’, J Int Med Res, 39 (4), 1306-18. PubMedID: 21986132