Видео лекции «Геропротекторы» — лекарства от старости — Остановить старение человека

«Видео лекции Геропротекторы»

Витамины и продолжительность жизни — Остановить старение человека

«Пожизненное употребление некоторых витаминов помогает предупредить рак, болезни сердца и увеличить продолжительность жизни человека»

2009 Melatonin: An Established Antioxidant Worthy of Use in Clinical Trials

«Oxidative stress plays a key role in the pathogenesis of aging and many metabolic diseases; therefore, an effective antioxidant therapy would be of great importance in these circumstances. Nutritional, environmental, and chemical factors can induce the overproduction of the superoxide anion radical in both the cytosol and mitochondria. This is the first and key event that lead to the activation of pathways involved in the development of several metabolic diseases that are related to oxidative stress. As oxidation of essential molecules continues, it turns to nitrooxidative stress because of the involvement of nitric oxide in pathogenic processes. Once peroxynitrite forms, it damages via two distinctive mechanisms. First, it has direct toxic effects leading to lipid peroxidation, protein oxidation, and DNA damage. This mechanism involves the induction of several transcription factors leading to cytokine-induced chronic inflammation. Classic antioxidants, including vitamins A, C, and E, have often failed to exhibit beneficial effects in metabolic diseases and aging. Melatonin is a multifunctional indolamine that counteracts virtually all pathophysiologic steps and displays significant beneficial actions against peroxynitrite-induced cellular toxicity. This protection is related to melatonin’s antioxidative and antiinflammatory properties. Melatonin has the capability of scavenging both oxygen- and nitrogen-based reactants, including those formed from peroxynitrite, and blocking transcriptional factors, which induce proinflammatory cytokines. Accumulating evidence suggests that this nontoxic indolamine may be useful either as a sole treatment or in conjunction with other treatments for inhibiting the biohazardous actions of nitrooxidative stress.»

2008 Interactions of the advanced glycation end product inhibitor pyridoxamine and the antioxidant α-lipoic acid on insulin resistance in the obese Zucker rat

«The average initial body weight did not differ among the various obese Zucker groups, and the average final body weight of the obese groups treated individually with PM (OP group) or R-ALA (OR group) were also not different compared with those of the obese vehicle-treated group (OV) (Fig. 1A). However, the average final body weight of the obese animals treated with the combination of PM and R-ALA (OPR group) was approximately 38 g or 9% less (P < .05) compared with that of the OV group. Both the initial and final body weight of the vehicle-treated lean Zucker rats (LV group) were significantly less (P < .05) compared with those of the OV group.»

2013 Zinc Supplementation Alters Plasma Aluminum and Selenium Status of Patients Undergoing Dialysis: A Pilot Study

After two-month Zn treatment, these patients had higher plasma Zn and Se concentration, reduced plasma Al concentration and oxidative stress.

End stage renal disease patients undergoing long-term dialysis are at risk for abnormal concentration of certain essential and non-essential trace metals and high oxidative stress. We evaluated the effects of zinc (Zn) supplementation on plasma aluminum (Al) and selenium (Se) concentration and oxidative stress in chronic dialysis patients. Zn-deficient patients receiving continuous ambulatory peritoneal dialysis or hemodialysis were divided into two groups according to plasma Al concentration (HA group, Al > 50 μg/L; and MA group, Al > 30 to ≤ 50 μg/L). All patients received daily oral Zn supplements for two months. Age- and gender-matched healthy individuals did not receive Zn supplement. Clinical variables were assessed before, at one month, and after the supplementation period. Compared with healthy subjects, patients had significantly lower baseline plasma Se concentration and higher oxidative stress status. After two-month Zn treatment, these patients had higher plasma Zn and Se concentration, reduced plasma Al concentration and oxidative stress. Furthermore, increased plasma Zn concentration were related to the concentration of Al, Se, oxidative product malondialdehyde (MDA), and antioxidant enzyme superoxide dismutase activities. In conclusion, Zn supplementation ameliorates abnormally high plasma Al concentration and oxidative stress and improves Se status in long-term dialysis patients.

2014 Chronobiology and Obesity: Interactions between Circadian Rhythms and Energy Regulation

Mice deficient in a circadian gene (Bmal1) had defects in insulin secretion, both at base levels and in response to glucose stimulation. These mice were highly susceptible to diabetes.

2017 Antioxidant effects of resveratrol in the cardiovascular system

«The antioxidant effects of resveratrol (3,5,4'‐trihydroxy‐trans‐stilbene) contribute substantially to the health benefits of this compound. Resveratrol has been shown to be a scavenger of a number of free radicals. However, the direct scavenging activities of resveratrol are relatively poor. The antioxidant properties of resveratrol in vivo are more likely to be attributable to its effect as a gene regulator. Resveratrol inhibits NADPH oxidase‐mediated production of ROS by down‐regulating the expression and activity of the oxidase. This polyphenolic compound reduces mitochondrial superoxide generation by stimulating mitochondria biogenesis. Resveratrol prevents superoxide production from uncoupled endothelial nitric oxide synthase by up‐regulating the tetrahydrobiopterin‐synthesizing enzyme GTP cyclohydrolase I. In addition, resveratrol increases the expression of various antioxidant enzymes. Some of the gene‐regulating effects of resveratrol are mediated by the histone/protein deacetylase sirtuin 1 or by the nuclear factor‐E2‐related factor‐2. In this review article, we have also summarized the cardiovascular effects of resveratrol observed in clinical trials.»

2000 Nicotinamide (vitamin B3) as an effective antioxidant against oxidative damage in rat brain mitochondria.

«Nicotinamide (vitamin B3) an endogenous metabolite, showed significant inhibition of oxidative damage induced by reactive oxygen species (ROS) generated by ascorbate-Fe2+ and photosensitization systems in rat brain mitochondria. It protected against both protein oxidation and lipid peroxidation, at millimolar concentration. Inhibition was more pronounced against oxidation of proteins than peroxidation of lipids. Chemically related endogenous compounds, tryptophan and isonicotinic acid, showed comparable inhibitory properties. The protective effect observed, at biologically relevant concentration, with nicotinamide was more than that of the endogenous antioxidants ascorbic acid and alpha-tocopherol. Hence our studies suggest that nicotinamide (vitamin B3) can be considered as a potent antioxidant capable of protecting the cellular membranes in brain, which is highly susceptible to prooxidants, against oxidative damage induced by ROS.»

2001 Chemopreventive activity of Withania somnifera in experimentally induced fibrosarcoma tumours in Swiss albino mice.

"The current experimental work deals with the chemopreventive studies of a hydroalcoholic extract of Withania somnifera roots, against 20-methylcholanthrene induced fibrosarcoma tumours in Swiss albino mice. A single subcutaneous injection of 200 microg 20-methylcholanthrene in 0.1 mL of dimethylsulphoxide into the thigh region of mice produced a high incidence (96%) of tumours. Oral treatment of animals with 400 mg/kg body weight of Withania somnifera extract (one week before injecting 20-methylcholanthrene and continued until 15 weeks thereafter) significantly reduced the tumour incidence, tumour volume and enhanced the survival of the mice, compared with 20-methylcholanthrene injected mice. The tumour incidence was also delayed in the treatment group when compared with 20-methylcholanthrene injected mice. Liver biochemical parameters revealed a significant modulation of reduced glutathione, lipid peroxides, glutathione-S-transferase, catalase and superoxide dismutase in extract treated mice compared with 20-methylcholanthrene injected mice. The mechanism of chemopreventive activity of Withania somnifera extract may be due to its antioxidant and detoxifying properties."

2008 Synergistic effect of combination of phenethyl isothiocyanate and sulforaphane or curcumin and sulforaphane in the inhibition of inflammation.

«Accumulating evidence from epidemiologic and clinical studies indicates that chronic inflammatory disorders harbor an increased risk of cancer development. Curcumin (CUR) has been strongly linked to the anti-inflammatory effect. On the other hand, isothiocyanates such as sulforaphane (SFN) and phenethyl isothiocyanate (PEITC) are strong phase-II detoxifying/antioxidant enzymes inducer. Therefore it is interesting to see if combination of these drugs can inhibit inflammation with higher combined efficacies.»

«We report that combination of PEITC + SFN or CUR + SFN has a synergistic effect in down-regulating inflammation markers like TNF, IL-1, NO, PGE2. The synergism is probably due to the synergistic induction of phase II/antioxidant enzymes including heme-oxygenase1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1).»

2008 Intestinal tumour chemoprevention with the antioxidant lipoic acid stimulates the growth of breast cancer.

«Stimulation of breast cancer growth and inhibition of intestinal tumours by LA indicate that diverse growth control mechanisms are modulated by LA in different organs. Concern is raised about the use of LA for cancer chemoprevention.»

2008 The antioxidant effects of melatonin in surgical brain injury in rats.

«The study suggests that low-dose melatonin may provide neuroprotective effects against SBI. Further studies are needed to confirm this. More importantly, the findings of the study stress the need to carefully reassess safety issues with high doses of melatonin, which is considered to be a practically non-toxic drug.»

2010 Effect of extract of Withania Somnifera on dehydration-induced oxidative stress-related uremia in male rats.

"Dehydration or water deprivation in the body decreases urinary excretion and allows urea and other protein waste products to accumulate in the blood. The aim of the present study is to evaluate the association of uremia and oxidative stress by applying the herbal plant Withania somnifera (W. somnifera) (Aswagandha). The study was performed on male Wister strain rats in which, dehydration was achieved by water withdrawal. A total of 18 rats were studied and were randomly divided into three Groups: Group-1, control, Group-2, only dehydration and Group-3, dehydration + administration of aqueous root extract of W. somnifera, orally (50 mg/100 gm body weight/day) for 25 days. After 25 days of treatment, it was observed that the body weight of Group-3 animals had increased significantly, while that in Group-2 had decreased significantly. The liver enzymes in both blood and kidneys did not show any significant change in the three groups implying absence of any toxicity of the root extract. In Group-2 animals, the serum urea and creatinine levels increased sig-nificantly when compared with animals in Groups-1 and 3. The low levels of serum urea and crea-tinine in Group-3 animals indicates the protective effect of the plant extract against renal injury caused by dehydration. Dehydration-induced oxidative stress was established in our study by noting the low activities of super-oxide dismutase and catalase, both important antioxidant enzymes, in Group-2 animals; both enzymes were stabilized in animals of Groups-3 and 1. In conclusion, it is hypothesized that there is an antioxidative role of W. somnifera resulting in reducing the extent of renal injury as a result of oxidative stress."

2010 Antioxidant and anti-inflammatory effects of resveratrol in airway disease.

«Respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are a significant and increasing global health problem. These diseases are characterized by airway inflammation, which develops in response to various stimuli. In asthma, inflammation is driven by exposure to a variety of triggers, including allergens and viruses, which activate components of both the innate and acquired immune response. In COPD, exposure to cigarette smoke is the primary stimulus of airway inflammation. Activation of airway inflammatory cells lead to the release of excessive quantities of reactive oxygen species (ROS), resulting in oxidative stress. Antioxidants provide protection against the damaging effects of oxidative stress and thus may be useful in the management of inflammatory airways disease. Resveratrol, a polyphenol that demonstrates both antioxidative and anti-inflammatory functions, has been shown to improve outcomes in a variety of diseases, in particular, in cancer. We review the evidence for a protective role of resveratrol in respiratory disease. Mechanisms of resveratrol action that may be relevant to respiratory disease are described. We conclude that resveratrol has potential as a therapeutic agent in respiratory disease, which should be further investigated.»

2010 Sulforaphane activates heat shock response and enhances proteasome activity through up-regulation of Hsp27.

The major mechanism by which SFN, an electrophile, protects cells is believed to be through induction of direct and indirect antioxidant response, including up-regulation of glutathione and activation of
NF-E2-related factor 2 (Nrf2)-mediated phase II enzymes and
antioxidant enzymes that relieve cells from oxidant stress and carcinogenic attacks (11)

. However, its chemopreventive activity also includes other mechanisms, such as induction of cell cycle arrest and apoptotic pathways, inhibition of angiogenesis, and anti-inflammatory activity (9). Recently, SFN has been shown to enhance mammalian proteasome activity through induction of 26 S proteasome subunit PSMB5 (13). Both induction of PSMB5 and proteasome activation have been associated with antioxidant response mediated through the Keap1-Nrf2
pathway (13–16).

2013 Anti-inflammatory and antioxidant effects of resveratrol in healthy smokers a randomized, double-blind, placebo-controlled, cross-over trial.

«Because resveratrol has anti-inflammatory, anti-oxidant, and hypotriglyceridemic effects, its supplementation may beneficially affect the increased cardiovascular risk of healthy smokers.»

2013 Attenuation of oxidative damage-associated cognitive decline by Withania somnifera in rat model of streptozotocin-induced cognitive impairment.

"Oxidative stress is a critical contributing factor to age-related neurodegenerative disorders. Therefore, the inhibition of oxidative damage, responsible for chronic detrimental neurodegeneration, is an important strategy for neuroprotective therapy. Withania somnifera (WS) extract has been reported to have potent antioxidant and free radical quenching properties in various disease conditions. The present study evaluated the hypothesis that WS extract would reduce oxidative stress-associated neurodegeneration after intracerebroventricular injection of streptozotocin (ICV-STZ) in rats. To test this hypothesis, male Wistar rats were pretreated with WS extract at doses of 100, 200, and 300 mg/kg body weight once daily for 3 weeks. On day 22nd, the rats were infused bilaterally with ICV-STZ injection (3 mg/kg body weight) in normal saline while sham group received only saline. Two weeks after the lesioning, STZ-infused rats showed cognitive impairment in the Morris water maze test. The rats were sacrificed after 3 weeks of the lesioning for the estimation of the contents of lipid peroxidation, reduced glutathione, and activities of glutathione reductase, glutathione peroxidase, and catalase. Pretreatment with WS extract attenuated behavioral, biochemical, and histological alterations significantly in dose-dependent manner in the hippocampus and cerebral cortex of ICV-STZ-infused rats. These results suggest that WS affords a beneficial effect on cognitive deficit by ameliorating oxidative damage induced by streptozotocin in a model of cognitive impairment."

2013 Bmal1 and β-cell clock are required for adaptation to circadian disruption, and their loss of function leads to oxidative stress-induced β-cell fai...

Keywords: ARNTL Transcription Factors;Adaptation, Physiological;Animals;Antioxidants;Circadian Rhythm;Diabetes Mellitus, Experimental;Gene Expression Regulation;Glucose;Hyperglycemia;Insulin;Insulin-Secreting Cells;Ion Channels;Male;Mice;Mice, Transgenic;Mitochondrial Proteins;Oxidative Stress;Reactive Oxygen Species;Uncoupling Protein 2

Effect of Nrf2 activators on release of glutathione, cysteinylglycine and homocysteine by human U373 astroglial cells.

GSH levels increased dose-dependently in response to all four drugs.
Sulforaphane produced the most potent effect, increasing GSH by up to 2.4-fold. PC-Res increased GSH up to
1.6-fold, followed by TBHQ (1.5-fold) and LA (1.4-fold).

While the order of drug potency remained almost the same for boosting GSH and CysGly, all drugs were able to increase GSH levels between 1.2 and 1.4 times more than they were able to
increase CysGly (Table 1).

2014 An antioxidant and multivitamin supplement reduced improvements in VO₂max.

«The aim of this study was to investigate the effect of an antioxidant supplement on training induced changes in VO₂max in well-trained subjects. In a double-blinded placebo controlled design, a total of 40 amateur soccer players and 14 multi sports athletes were block-randomised into a placebo group or an antioxidant supplemented group (SUP). The SUP group consumed two commercially available antioxidant/vitamin supplements for 6 weeks according to manufacturer instructions (LifePak® Essentials Super A) and the placebo group took a similar amount of placebo tablets. Before and after the supplementation period, the athletes were tested for skin carotenoid score and VO₂max. During the supplementation period all subjects continued their normal training in the preparation phase of the season. Six week supplementation with the antioxidant vitamin/mineral supplement increased skin carotenoid score by 27 ± 6% while no change was observed in the placebo group. VO₂max increased by 5.6 ± 2.0% in the placebo group while no change was observed in the SUP group. The relative increase in VO₂max was significantly higher in the placebo group than in the SUP group. In conclusion, the antioxidant vitamin/mineral supplement used in this study seemed to reduce training efficiency indicated by the lack of increase in VO₂max in the SUP group.»

2016 NRF2 activation by antioxidant antidiabetic agents accelerates tumor metastasis.

«Cancer is a common comorbidity of diabetic patients; however, little is known about the effects that antidiabetic drugs have on tumors. We discovered that common classes of drugs used in type 2 diabetes mellitus, the hypoglycemic dipeptidyl peptidase-4 inhibitors (DPP-4i) saxagliptin and sitagliptin, as well as the antineuropathic α-lipoic acid (ALA), do not increase tumor incidence but increase the risk of metastasis of existing tumors. Specifically, these drugs induce prolonged activation of the nuclear factor E2-related factor 2 (NRF2)-mediated antioxidant response through inhibition of KEAP1-C151-dependent ubiquitination and subsequent degradation of NRF2, resulting in up-regulated expression of metastasis-associated proteins, increased cancer cell migration, and promotion of metastasis in xenograft mouse models. Accordingly, knockdown of NRF2 attenuated naturally occurring and DPP-4i-induced tumor metastasis, whereas NRF2 activation accelerated metastasis. Furthermore, in human liver cancer tissue samples, increased NRF2 expression correlated with metastasis. Our findings suggest that antioxidant that activate NRF2 signaling may need to be administered with caution in cancer patients, such as diabetic patients with cancer. Moreover, NRF2 may be a potential biomarker and therapeutic target for tumor metastasis.»

2016 Melatonin as an antioxidant: under promises but over delivers.

2017 Role of D-galactose-induced brain aging and its potential used for therapeutic interventions.

The effects of D-galactose-induced mitochondrial dysfunction and oxidative stress in the brain. D-galactose oxidized by galactose oxidase to form hydrogen peroxide (H2O2), leading to decrease in superoxide dismutase (SOD) (Hsieh et al., 2009). Increased H2O2 reacts with a reduced form of iron (Fe) to form hydroxide ions (OH-). The H2O2 and OH are both types of reactive oxygen species (ROS) and along with others can cause lipid peroxidation in the cell membranes and impair redox homeostasis, leading to neuronal damage.

In addition, several studies described that D-galactose induced the accumulation of brain mitochondrial DNA mutation (Chen et al., 2011; Du et al., 2012; Du et al., 2015; Zeng et al., 2014) through: 1) decreasing DNA-repairing enzymes (OGG1, pol ᵧ) (Chen et al., 2011), and 2) common deletion of mitochondrial DNA and impairing mitochondrial structures via the NOX-dependent pathway (Du et al., 2015).

Effect of D-galactose-induced apoptosis in the brain. D-galactose
promoted the apoptotic process (Qian et al., 2008). In addition to apoptosis, D-galactose promoted neuro-inflammation and neurodegeneration (Cui et al., 2006). The dosage from which D-galactose started inducing apoptosis was 100 mg- 500 mg/kg/day, duration was from 6 weeks to 9 weeks. (as shown in Table 2)

Effect of D-galactose-induced brain inflammation. D-galactose started inducing inflammation at a dosage of 50mg-180mg/kg/day and duration was from 6 weeks to 60 days.

Therapeutic approaches to brain mitochondrial aging induced by D-galactose:

The first one used R-alpha-lipoic acid which is an antioxidant abundant in yeast, liver, kidney, spinach, broccoli, and potatoes, to treat mitochondrial dysfunction (Long et al., 2007). One of the studies stated that 100 mg/kg/day of R-alpha-lipoic acid is used for prevention but not for intervention, dosage should be increased up to 180mg/kg/day (Inman et al., 2013).

Carvidilol, pioglitazone, curcumin and hesperidin have an antioxidant effect. These drugs have been used as an intervention to reverse D-galactose-induced mitochondrial dysfunction in a dose dependent manner.

The other therapeutic approaches to improve cognition with a dose-independent manner in the D-galactose model were fibroblast growth factor 21 (FGF21), salidroside, and tetrahydropalmatine (Banji et al., 2014; Gao et al., 2015; Kumar et al., 2009; Prakash and Kumar, 2013; Qu et al., 2016; Yang et al., 2016; Yu et al., 2015).

FGF21 acts on its receptors and prevents D-galactose-induced spatial learning and memory impairment by attenuating oxidative stress, inflammatory markers and renovating the activities of antioxidant enzymes and decreasing AGE formation, and TChE activity (Yu et al., 2015).

Many studies have proved that a daily intake of caffeine ameliorated cognitive decline in “non-demented” elderly men and women by the mechanism of reducing synaptic dysfunction, and the reduction in oxidative stress, apoptosis, neuro-inflammation and neurodegeneration (Ritchie et al., 2007; van Gelder et al., 2007).

2018 Sulforaphane as anticancer agent: A double-edged sword? Tricky balance between effects on tumor cells and immune cells.

«Sulforaphane (SFN) is a naturally occurring isothiocyanate derived from cruciferous vegetables such as broccoli. It has been reported to inhibit the growth of a variety of cancer, such as breast, prostate, colon, skin, lung, gastric or bladder cancer. SFN is supposed to act primarily as an antioxidant due to the activation of the Nrf2-Keap1 signaling pathway. This enhances the activity of phase II detoxifying enzymes and the trapping of free radicals. Finally, SFN induces cell cycle arrest or apoptosis of tumor cells. Here, we discuss effects of SFN on the immune defense system. In contrast to the situation in tumor cells, SFN acts pro-oxidatively in primary human T cells. It increases intracellular ROS levels and decreases GSH, resulting in inhibition of T cell activation and T cell effector functions. Regarding the use of SFN as an "anticancer agent" we conclude that SFN could act as a double-edged sword. On the one hand it reduces carcinogenesis, on the other hand it blocks the T cell-mediated immune response, the latter being important for immune surveillance of tumors. Thus, SFN could also interfere with the successful application of immunotherapy by immune checkpoint inhibitors (e.g. CTLA-4 antibodies and PD-1/PD-L1 antibodies) or CAR T cells. Therefore, a combination of SFN with T cell-mediated cancer immunotherapies does not seem advisable.»

1997 Antioxidant activity of glycowithanolides from Withania somnifera.

"Antioxidant activity of active principles of Withania somnifera, consisting of equimolar concentration of sitoindosides VII-X and withaferin A, was investigated for their effects on rat brain frontal cortical and striatal concentration of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX). Results were compared with effects induced by deprenyl, an agent with well documented antioxidant activity. Active glycowithanolides of W. somnifera (WSG) (10 and 20 mg/kg, i.p.), administered once daily for 21 days, induced a dose-related increase in SOD, CAT and GPX activity in frontal cortex and striatum, which was statistically significant on days 14 and 21, except with the lower dose of WSG on GPX activity, where the effect was evident only on day 21. The data were comparable to those induced by deprenyl (2 mg/kg/day, i.p.) with respect to SOD, CAT and GPX activities, which were evident by day 14. These findings are consistent with the therapeutic use of W. somnifera as an Ayurvedic rasayana and medhyarasayana. Antioxidant effect of active principles of W. somnifera may explain, at least in part, the reported antistress, immunomodulatory, cognition-facilitating, anti-inflammatory and anti-aging effects produced by them in experimental animals, and in clinical situations."

31 Ashwagandha Benefits + Side Effects, Dosage - Selfhacked

"I've been taking Ashwagandha for 7 years on and off.  When you read the research, you start to question what Ashwagandha doesn't treat.  It's one of the best all-around supplements for general health."

Антистарение мозга. Часть 1 - YouTube

«B12, D3, глутатион, окислительный стресс, ацетилцистеин, антиоксиданты, сульфорафан, метформин»

Антистарение мозга. Часть 1 - YouTube

«B12, D3, глутатион, окислительный стресс, ацетилцистеин, антиоксиданты, сульфорафан, метформин»