Senescence is a permanent cell cycle arrest that is accompanied by changes in cell morphology and physiology occurring
in vitro
and
in vivo
. Senescence evolved as a beneficial response to damage ...promoting wound healing, limiting fibrosis, fighting against cancer and helping embryonic development. However, excessive accumulation of senescent cells is considered to play a substantial role in the development of aging-related diseases and other morphological and physiological changes associated with aging. Therefore, the aim of many researchers is to find out a way to eliminate senescent cells and improve the health condition of aging people. Bioactive compounds
e.g.
polyphenols, vitamins, phenols, carotenoids, ginsenosides, omega-3 fatty acids, and compounds isolated from algae (phloroglucinol, sargachromal) are known to affect important biological functions. Recent
in vitro
studies have revealed that they can protect different types of cells against stress induced senescence (SISP), delay replicative senescence, rejuvenate senescent cells and exert senolytic effects. This review summarizes how the biological compounds listed above affect cell morphology, cell proliferation, specific cell functions, the activity of senescence-associated β-galactosidase (SA-β-gal), the shortening of telomeres and reduction of telomerase activity, production of intracellular reactive oxygen species (ROS) and lipid peroxidation products, expression of antioxidant enzymes, expression of p53 and p21 - key effectors of cell cycle arrest leading to senescence - and expression of some key components of senescence associated secretory phenotype (SASP) in replicative senescence, stress induced senescence (SISP) and under conditions which may lead to the development of senescence such as UV-A and UV-B irradiation of cells and the production of matrix metalloproteinases (a component of the SASP) in cells. Finally, future perspectives of this research are discussed.
Senescence is a permanent cell cycle arrest that is accompanied by changes in cell morphology and physiology occurring
in vitro
and
in vivo
.
Senescence is an irreversible permanent cell cycle arrest accompanied by changes in cell morphology and physiology. Bioactive compounds including tocotrienols (vitamin E) can affect important ...biological functions. The aim of this study was to investigate how γ- and δ-tocotrienols can affect stress-induced premature senescence. We established two different models of premature stress senescence by induction of senescence with either hydrogen peroxide or etoposide in human lung fibroblasts MRC-5 (ECACC, England). We observed increased percentage of cells with increased SA-β-galactosidase activity, decreased cell viability/proliferation and increased level of p21 in both models. In addition, γ-tocotrienol or δ-tocotrienol (both at concentrations of 150, 200 and 300 μM) were added to the cells along with the inductor of senescence (cotreatment). We have found that this cotreatment led to the decrease of cell viability/proliferation in both models of premature stress senescence, but did not change the percentage of senescent cells. Moreover, we detected no expression of caspase-3 or apoptotic DNA fragmentation in any models of premature stress senescence after the cotreatment with γ- as well as δ-tocotrienols. However, an increased level of autophagic protein LC-3 II was detected in cells with hydrogen peroxide—induced senescence after the cotreatment with γ-tocotrienol as well as δ-tocotrienol. In case of etoposide—induced senescence only δ-tocotrienol cotreatment led to an increased level of LC-3 II protein in cells. According to our work δ-tocotrienol is more effective compound than γ-tocotrienol.
Graphic abstract
Epidemiological studies have suggested an increased vascular risk in patients with multiple sclerosis (MS). There is increasing evidence of the beneficial effects of GLP-1 agonists (GLP-1a) in ...preventing vascular complications and slowing the progression of neurodegeneration. Our objective was to explore the changes in the endothelial function of MS patients after 12 months of GLP-1a therapy. We also explored the role of lipoprotein subfractions and the antioxidant capacity of plasma.
MS patients were enrolled in a prospective, unicentric study. GLP-1a (dulaglutide) was administered to 13 patients. The control population consisted of 12 subjects. Endothelial function was determined by peripheral arterial tonometry and expressed as reperfusion hyperemia index (RHI). Trolox equivalent antioxidant capacity (TEAC) was used to assess the total antioxidant capacity of the plasma. The levels of lipoprotein subfractions were evaluated.
The GLP-1a group did not have a significant change in their RHIs after 12 months (2.1 ± 0.6 vs. 2.1 ± 0.7;
= 0.807). However, a significant increase in their TEACs was observed (4.1 ± 1.4 vs. 5.2 ± 0.5 mmol/L,
= 0.010). On the contrary, the subjects in the control group had a significant worsening of their RHIs (2.1 ± 0.5 vs. 1.8 ± 0.6;
= 0.030), without significant changes in their TEACs. Except for a significant decrease in very-low-density lipoprotein (VLDL) (30.8 ± 10.2 vs. 22.6 ± 8.3 mg/dL,
= 0.043), no other significant changes in the variables were observed in the control group. VLDL levels (beta = -0.637,
= 0.001), the use of GLP-1a therapy (beta = 0.560,
= 0.003), and small LDL (beta = 0.339,
= 0.043) were the only significant variables in the model that predicted the follow-up RHI.
Our results suggest that the application of additional GLP-1a therapy may have atheroprotective and antioxidant effects in MS patients with high MS activity and thus may prospectively mitigate their vascular risk. However, the lipoprotein profile may also play an important role in the atherogenic risk of MS subjects.
This study was designed to investigate whether oxidative stress, nitric oxide (NO) deficiency and/or endothelial dysfunction (ED) are present in young borderline hypertensive rats (BHR) and whether ...these pathologies can be causally involved in the initiation of blood pressure (BP) increases. Additionally, we tested the hypothesis that crowding stress, experienced during the peripubertal period, may produce persistent or delayed disorders in corticosterone release, NO synthesis, oxidative status and/or endothelial function that could accelerate BP increases. To test these hypotheses, 5-week-old male BHR and normotensive Wistar-Kyoto rats (WKY) were either kept in control conditions (for 2 and 4 weeks, respectively) or exposed to social stress produced by crowding for 2 weeks (stress). After cessation of crowding, a group of rats of each phenotype was kept in control conditions for the next 2 weeks (post-stress). Systolic BP of 5-week-old BHR was significantly increased vs. age-matched WKY (127 ± 3 vs. 104 ± 3 mmHg,
< 0.01) and remained significantly higher throughout the course of the experiment. Despite elevated BP, no signs of oxidative damage to plasma lipids, NO deficiency or ED were observed in control BHR vs. age-matched WKY. Crowding stress elevated plasma corticosterone and accelerated BP increases only in BHR; these effects persisted 2 weeks post-stress. Crowding failed to induce oxidative damage to plasma lipids in either phenotype, but it produced persistent decreases in NO production in the hypothalamus and brainstem of both strains of rats, as well as in the hearts of BHR. In contrast, crowding failed to reduce NO production in the aortae or acetylcholine-induced relaxations of the femoral arteries in both strains investigated. However, significantly reduced aortic NO production was observed in BHR 2 weeks post-stress vs. age-matched controls, which was in agreement with reduced NO-dependent components of vasorelaxation. In conclusion, this study's data showed that oxidative stress, NO deficiency and ED are not causally involved in initiation of blood pressure increase in BHR. However, exposure to stressful environments produced persistent increases in plasma corticosterone and reductions of brain and cardiac NO production followed by a delayed decrease in the NO-dependent component of endothelium-dependent relaxation-changes that collectively accelerated BP increases only in BHR.
Obstructive sleep apnea (OSA) is a disorder with a significant risk for cardiovascular diseases. Dyslipidemia and redox imbalance belong to potential mechanisms linking OSA with the development of ...vascular diseases. The main aim of this study was the evaluation of the presence of lipid abnormalities in OSA patients, focusing on small dense low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions and determination of the redox imbalance by evaluating the marker of oxidative damage to plasma lipids - lipoperoxides.
The study included 15 male subjects with polysomnographically confirmed OSA and 16 male healthy controls. Plasma levels of total cholesterol, LDL and HDL and their subfractions, triacylglycerols and lipoperoxides were determined in all study individuals. Plasma LDL and HDL subfractions were separated by the Lipoprint system which is a polyacrylamide gel electrophoresis. Lipoperoxide levels were determined spectrophotometrically.
OSA patients had significantly higher triacylglycerols, total cholesterol and LDL-cholesterol compared to healthy controls. HDL cholesterol was not significantly different. Of the LDL and HDL subfractions, OSA patients had significantly lower levels of atheroprotective LDL1 and large HDL subfractions and significantly higher levels of atherogenic small dense LDL3-7 and HDL8-10 subfractions. Lipoperoxide levels in patients with OSA were significantly elevated compared to healthy individuals.
The lipoprotein pro-atherogenic phenotype was found in individuals with OSA characterized by increased levels of atherogenic lipoprotein subfractions and reduced levels of atheroprotective subfractions. In addition, a plasma redox imbalance was found in patients with OSA compared to controls by detecting higher oxidative damage to lipids. Abnormalities in lipoprotein levels in patients with OSA, as well as the redox imbalance, could lead to an acceleration of the atherosclerotic process in predisposed individuals and thus represent a significant risk factor for vasular diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Exposure to ETS (environmental tobacco smoke) is one of the most toxic environmental exposures.
To investigate the association of ETS with physiological, biochemical, and psychological indicators, as ...well as with urine antioxidant capacity (AC) and oxidative damage to lipids in a pilot sample of healthy pregnant women.
Exposure to ETS was investigated via a validated questionnaire, and urine cotinine and the marker of oxidative damage to lipids via 8-isoprostane concentrations using an ELISA kit. Urine AC was determined by the spectrophotometric Trolox-equivalent antioxidant capacity (TEAC) method. From a sample of pregnant women (
= 319, average age 30.84 ± 5.09 years) in 80, the levels of cotinine and oxidative stress markers were analyzed.
Among the 80 pregnant women, 5% (7.4% confirmed by cotinine) reported being current smokers and 25% reported passive smoking in the household (18.8% confirmed by cotinine). The Kappa was 0.78 for smokers and 0.22 for ETS-exposed nonsmokers. Pregnant women in the ETS-exposed group had significantly reduced AC compared to both the nonsmoker (ETS-) and the smoker groups (
< 0.05). Nonsmokers had significantly lower levels of 8-isoprostane than smokers (
< 0.01) and ETS-exposed nonsmokers (
< 0.05). Correlations between urine levels of cotinine and AC were positive in ETS-exposed nonsmokers.
A harmful association of active and passive smoking and oxidative stress parameters among pregnant women has been indicated.
Several studies have reported that the administration of various nanoparticles in vivo can cause oxidative stress. The combination of ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) ...and acute stress was selected because, during intravenous application of a contrast agent, patients are exposed to psycho-emotional stress. This study was designed to investigate the effect of acute stress and USPIONs on selected markers of oxidative stress (antioxidant capacity, superoxide dismutase, glutathione peroxidase and catalase activities, levels of advanced oxidation protein products, protein carbonyls, lipoperoxides and 8-isoprostanes) in plasma and erythrocytes in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). In the WKY and SHR groups, there was a significant main effect of genotype between groups on studied markers except protein carbonyls and lipoperoxides. In SHR, the combination of acute stress and USPIONs increased the antioxidant capacity of plasma and the selected enzyme activities of erythrocytes. In WKY, the combination of acute stress and USPIONs decreased the antioxidant capacity of erythrocytes and reduced levels of advanced oxidation protein products in plasma. Our study points to the fact that, when hypertensive subjects are treated with iron oxide nanoparticles, caution should be taken, especially in stress conditions, since they seem to be more vulnerable to oxidative stress produced by USPIONs.
Vitamin D is neccessary for regulation of calcium and phosphorus metabolism in bones, affects imunity, the cardiovascular system, muscles, skin, epithelium, extracellular matrix, the central nervous ...system, and plays arole in prevention of aging-associated diseases. Vitamin D receptor is expressed in almost all types of cells and its activation leads to modulation of different signaling pathways. In this review, we have analysed the current knowledge of 1,25-dihydroxyvitamin D
or 25-hydroxyvitamin D
effects on metabolism of cells important for the function of the cardiovascular system (endothelial cells, vascular smooth muscle cells, cardiac cells and pericytes), tissue healing (fibroblasts), epithelium (various types of epithelial cells) and the central nervous system (neurons, astrocytes and microglia). The goal of this review was to compare the effects of vitamin D on the above mentioned cells in in vitro conditions and to summarize what is known in this field of research.
This study investigated the contribution of blood oxidative stress (OS) to the development of hypertension, as well as sex differences in the antioxidant defense system (ADS) in genetic models of ...hypertension. Nine-week-old normotensive Wistar-Kyoto (WKY) rats, borderline hypertensive rats (BHR) and spontaneously hypertensive rats (SHR) of both sexes were used. Systolic blood pressure (SBP) was determined by tail-cuff plethysmography, the trolox equivalent antioxidant capacity (TEAC) and the concentration of lipid peroxides (LP) were determined in plasma. The activity of the antioxidant enzymes Cu/Zn-superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) was determined in erythrocytes. SBP was significantly elevated in BHR and SHR in both sexes. BHR and SHR males had a higher SBP than the respective females. Sex-dependent differences in the ADS were found only in SHR, in which TEAC, SOD and CAT were significantly higher in males than in females. No differences in TEAC, SOD, CAT and GPx were observed between BHR (males and females) and WKY controls. LP levels were similar in all the groups investigated. Significant positive correlations were observed between SBP and both SOD and CAT. TEAC correlated positively with SOD and LP. As no signs of oxidative damage to lipids were found in young BHR and SHR of either sex, OS in the blood does not seem to be causatively related to the development of hypertension in these rats. However, despite activated antioxidant defenses, the positive correlation between plasma TEAC and LP suggests that oxidative damage is progressing slowly and therefore it seems to be a consequence rather than the cause of hypertension.
Obstructive sleep apnea (OSA) activates several pathophysiological mechanisms which can lead to the development of vascular diseases. Endothelial dysfunction (ED) is an initial step in the ...development of atherosclerosis. The association between ED and OSA has been described in several studies, even in previously healthy subjects. High-density lipoproteins (HDL) were generally considered to be atheroprotective, and low-density lipoprotein (LDL) to be an atherogenic component of lipoproteins. However, recent findings suggest a pro-atherogenic role of small HDL subfractions (8-10) and LDL subfractions (3-7). This study aimed to evaluate the relationship between endothelial function and lipid subfractions in previously healthy OSA subjects.
We prospectively enrolled 205 subjects with sleep monitoring. Plasma levels of triacylglycerols, total cholesterol, LDL, HDL, and their subfractions were assessed. Endothelial function was determined using peripheral arterial tonometry, and reperfusion hyperemia index (RHI) was assessed.
Plasma levels of small and intermediate HDL subfractions have statistically significant pro-atherogenic correlations with endothelial function (
= 0.015 and
= 0.019). In other lipoprotein levels, no other significant correlation was found with RHI. In stepwise multiple linear regression analysis, small HDL (beta = -0.507,
= 0.032) was the only significant contributor in the model predicting RHI.
In our studied sample, a pro-atherogenic role of small HDL subfractions in previously healthy subjects with moderate-to-severe OSA was proven.
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