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EGCG Extends Lifespan - Modern Healthspan Study ReviewEGCG and aging -
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J Invest Dermatol. Download references. This work is supported by National Natural Science Foundation of China and Scientific Research Project of Liaoning Province School of Pharmacy, China Medical University, Shenyang , China.
You can also search for this author in PubMed Google Scholar. BBW conceived and designed the experiments; BBW, XZ, and WFY performed the experiments; MYL analyzed the data; MJW wrote and reviewed the paper.
All authors read and approved the final manuscript. Correspondence to Min-jie Wei. Reprints and permissions. Wei, Bb. et al. Increased BBB permeability contributes to EGCG-caused cognitive function improvement in natural aging rats: pharmacokinetic and distribution analyses.
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You have full access to this article via your institution. Ginsenoside Rg1 in neurological diseases: From bench to bedside Article 15 November Materials and methods Animals and treatment Male pathogen-free Sprague—Dawley rats were kindly provided by the Experimental Animal Center of China Medical University Shenyang, China.
MWM test The cognitive performance of 6-week-old rats and 1-year-old natural aging rats was evaluated in the MWM, including the navigation test and probe trial.
ELISA assay After the tissue samples were cut, phosphate-buffered saline PBS pH 7. Table 1 Optimized MRM parameters for EGCG and IS Full size table.
Full size image. Results EGCG treatment ameliorated learning and memory impairment in aging rats with CI To distinguish between 1-year-old natural aging rats with and without CI, we first performed MWM to evaluate the cognitive performance in natural aging rats.
Table 2 Linear ranges, regression equations, and correlation coefficients of EGCG in rat plasma and tissues Full size table. Discussion In the present study, we were first inspired by the different pharmacokinetic and distribution characteristics brain, heart, lung, intestine, kidney, spleen, testes, and liver between young rats and aging rats with CI, which suggested that the increased BBB permeability in aging rats played an important role in the anti-AD efficacy of EGCG treatment demonstrated by improvements in CI.
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CAS PubMed Google Scholar Yang SL, Liu MY, Zhong X, Du K, Wei MJ. To exclude any effects on development, the incubation period with compounds started at the L4 stage by transferring nematodes to the respective NGM plates [ 84 ].
Louis, MO, USA to prevent progeny formation. After 16 h, we transferred animals to respective treatment groups and harvested them at the indicated time points [ 18 ].
According to standard protocols, all lifespan assays were performed at 20°C as previously described [ 18 , 19 ]. Briefly, the C. Eggs of nematodes were transferred to NGM plates with fresh OP50 bacteria to allow hatching and development.
After approximately 64 h, at the L4 stage, we moved nematodes manually to freshly prepared NGM plates containing the respective compounds and supplied them with a lawn of OP50 HIT.
During the first 10—14 days, nematodes were transferred to freshly prepared NGM treatment plates every day and later every second day. Nematodes without any reaction to gentle stimulation were classified as dead. Nematodes that crawled off the plate or suffered from non-natural death like internal hatching were censored and excluded from statistics on the day of premature death.
Notably, for lifespan analysis using BHA, nematodes were propagated on BHA-containing NGM plates for four generations before synchronization; the same applied for the respective DMSO controls.
Following the L4 stage, nematodes were treated with 0. Afterward, we transferred single worms into S-buffer containing 0. Movements of single worms within the liquid system were recorded for 20 seconds by a digital CCD camera Moticam , Motic, St.
Ingbert, Germany coupled microscope SMZ , Motic, St. Ingbert, Germany equipped with Motic Images Plus 2. We analyzed the videos using the DanioTrack software Loligo Systems, Tjele, Denmark , subtracting the background and determining the center of gravity of all object pixels compared to the background.
Resistance to lethal oxidative stress by paraquat Sigma-Aldrich, Munich, Germany was assessed as previously described [ 18 , 19 ]. Briefly, worms were treated with 0. Afterward, we transferred worms into well plates: 6 nematodes in μl of S-buffer, containing freshly dissolved 50 mM paraquat.
Dead worms were scored every hour until all control worms were dead. Briefly, we treated worms with 0. Worms were also washed twice with S-buffer and transferred into the DW1 chamber to monitor oxygen consumption for 10 mins.
Afterward, we collected worms for Bradford protein determination [ 86 ]. Before the ROS measurement, MitoTracker Red CM-H2X ROS Invitrogen, Carlsbad, CA, USA incubation plates were prepared as previously described [ 19 ]. Worms were additionally washed twice with S-buffer and transferred to freshly prepared MitoTracker Red CM-H2X incubation NGM plates containing μl of OP50 HIT mixed with μl freshly prepared MitoTracker Red CM-H2X stock solution μM.
After 2 h at 20°C, worms were washed off MitoTracker Red CM-H2X incubation NGM plates and transferred to NGM agar plates with 0. Fluorescence intensity was measured on a microplate reader FLUOstar Optima, BMG Labtech, Offenburg, Germany using well-scanning mode ex: nm; em: nm. We collected worms from plates for Bradford protein determination [ 86 ].
We placed an equal number of nematodes on the NGM plates containing 0. After collection and two subsequent washes in S-buffer, worm pellets were resuspended in the incubation buffer. The latter were placed in 10 cm Petri dishes together with a second 4 cm Petri dish containing μl of 0.
Hence, each 10 cm dish was equipped with two 4 cm dishes, one carrying nematodes and the other containing KOH. We added nonradioactive glucose into each sample to reach a final concentration of 0. The 10 cm Petri dishes were covered, sealed with parafilm in an air-tight manner, and incubated at 20°C for 3 h.
Subsequently, an aliquot of μl of KOH was immersed in 4. to quantify the amount of trapped 14 CO 2. We treated nematodes with 0. After collection and washing with S-buffer twice, worm pellets were shock frozen in liquid nitrogen and grinded in a nitrogen-chilled mortar. The grinded samples were boiled with 4 M Guanidine-HCl at 99°C for 15 min to destroy ATPase activity [ 58 , 89 ].
ATP values were normalized to protein content using the Bradford assay [ 86 ]. After treating nematodes with 0. The produced formaldehyde was determined spectrophotometrically with 4-aminohydrazinomercapto-1, 2, 4-triazole Purpald, Applichem, Darmstadt, Germany.
We measured SOD activity photometrically with a tetrazolium salt, forming a water-soluble formazan dye upon reduction with a superoxide anion. We determined fat content by applying a triglyceride determination kit Roche, Mannheim, Germany as previously described [ 18 , 88 ] and normalized to protein content using the Bradford assay [ 86 ].
Briefly, worms were incubated with 0. We centrifuged μl of the homogenized extract and extracted the supernatant for protein determination. The heating was repeated once to dissolve all triglycerides. We measured the activity of complex I spectrophotometrically at nm in 1 ml of 25 mM potassium phosphate buffer containing 3.
Decylubiquinone and antimycin A were dissolved in DMSO as DCIP and NADH were dissolved in water as 10 mM for both. After being thawed, 30 μl of mitochondria were treated with μl of 10 mM Tris-Cl, pH 7.
Subsequently, 20 μl mitochondria fragments were preincubated in a μl incubation mixture without NADH for 3 mins. After 3 mins, we added 20 μl of 10 mM NADH into the incubation mixture and measured the absorbance at 20 s intervals for 2 mins. Briefly, rodents were fasted overnight and killed by cervical dislocation.
The washed liver fragments were placed into the tube with around 25 ml isolation buffer. The loose-fitting pestle was inserted, pressed down, and lifted four times, and then the tight-fitting pestle was applied in the same way twice.
The mixture was poured into the 50 ml polypropylene falcon tube and centrifuged at g for 10 min at 4°C. We carefully removed the fat on the top of the supernatant by using tissue paper.
The supernatant was extracted to a second polypropylene falcon tube centrifuged at g for 10 min at 4°C. Afterward, the fat was removed, the supernatant discarded, and the mitochondrial pellet resuspended in the remaining buffer. The suspension containing mitochondria was centrifuged again at g for 10 min at 4°C.
The supernatant was removed entirely, and the mitochondrial pellet was resuspended in μl isolation buffer as described above. The concentration of isolated mitochondria was determined with Bradford After recording basal respiration for 2 min, 0. After ADP was wholly consumed, the oxygen consumption rate slowed down, 5 mM succinate, and ADP were added to study complex II, III, IV activity.
At the end of each measurement 60 nM FCCP were supplied to check the viability of mitochondria. Data are expressed as means ±SD unless otherwise indicated. Statistical calculations were carried out using the log-rank test to compare significant distributions between the different groups in lifespan and stress resistance assays.
We performed all analyses using Microsoft Office Excel Microsoft, Albuquerque, NM, USA. performed experiments, analyzed, and visualized the data. and M. wrote the manuscript. Funding was acquired by M.
and C. All authors have read and agreed to the published version of the manuscript. elegans strains used in this work were provided by the Caenorhabditis Genetics Centre Univ. of Minnesota, USA , which is funded by NIH Office of Research Infrastructure Programs P40 OD Parts of this project are contained in a Ph.
thesis J. thesis C. is currently funded by an Erwin Schroedinger Abroad Fellowship JB Corina T. Madreiter-Sokolowski corina. madreiter medunigraz. Michael Ristow michael-ristow ethz. Navigate Home Editorial Board Information For Authors Advance Online Publications Current Issue Archive Scientific Integrity Publication Ethics and Publication Malpractice Statements Contact Special Collections Podcast News Room Interviews with Outstanding Authors.
Priority Research Paper Volume 13, Issue 19 pp — Cite this Article How to cite Tian J , Geiss C , Zarse K , Madreiter-Sokolowski CT , Ristow M ,. Abstract Green tea catechins are associated with a delay in aging.
Introduction Clinical trials and epidemiological studies have revealed health benefits associated with green tea consumption, including a significant reduction in systolic blood pressure [ 1 ] and fasting glucose [ 2 ] as well as weight loss in type 2 diabetes patients [ 3 ] and in women with central obesity [ 4 ].
Results EGCG and ECG promote lifespan, fitness, and stress resistance when applied at low doses Oral absorption and absolute bioavailability of green tea catechins are low in mammals [ 12 ], reaching total maximum plasma concentrations of 2.
Table 1. Lifespan results and statistical analysis. Strains, Compounds Max lifespan in days ± SD 10 th percentile Medium lifespan in days ± SD 50 th percentile Number of experiments n P value versus control Number of nematodes N2 DMSO p38 MAPK, NRF2, and FOXO are required for the lifespan extension induced by catechins As shown in Figure 2 , EGCG and ECG block complex I activity and, thus, induce a transient rise in ROS levels.
Discussion Green tea is one of the most widely consumed beverages worldwide [ 32 ]. Conclusions We conclude that applying the green tea catechins EGCG and ECG at a low dose extends the lifespan of C.
Methods Nematode strains and maintenance C. Compound treatment EGCG, ECG, and BHA dissolved in DMSO, reaching a stock concentration of 2.
Lifespan analyses According to standard protocols, all lifespan assays were performed at 20°C as previously described [ 18 , 19 ].
Locomotion assay Following the L4 stage, nematodes were treated with 0. Paraquat stress resistance assay Resistance to lethal oxidative stress by paraquat Sigma-Aldrich, Munich, Germany was assessed as previously described [ 18 , 19 ].
In this study, WI fibroblasts were treated with 0, 25, 50 and μM concentrations of EGCG simultaneously at population doubling PD The difference in life span between groups was analyzed to determine whether EGCG could prolong the cell replicative life span.
We dynamically monitored the senescence state, ROS, inflammatory factors and proliferative capacity in WI fibroblasts throughout their replicative life span. As expected, our results suggest that the number of cells positive for senescence-associated beta-galactosidase SA beta-gal activity at high population doublings were reduced by EGCG.
In addition, the percentage of cells that continued to incorporate EdU in the EGCG-treated cultures was increased in senescent WI fibroblasts. These findings are consistent with decline in the SA beta-gal activity and increased proliferation at PD 35 and 45 in the EGCG-treated cultures relative to the control cultures.
In addition, it has been reported that rats with acetic acid-induced colitis showed an increase in the activity of SOD in the EGCG-treated group when compared with that in the placebo or control group. We postulated that the alleviation of endogenous oxidative and inflammation production through EGCG treatments might reduce the endogenous oxidative and inflammation responses, and that these might underlie the increased replicative life span observed in EGCG-treated cultures.
In the current study, we measured the levels of oxidative stress and inflammation in the presence or absence of EGCG at each stages of the WI fibroblasts. As we expected, EGCG treatments showed decreased levels of oxidative stress and inflammation factors relative to controls at PD 35 and Therefore, we propose that EGCG exerts the effects of prolonging replicative life span by mitigating the oxidative stress and inflammation in WI fibroblasts.
With senescent-passage cells, we determined the age-associated effects with signaling through gene sequencing. The study was conducted by using the methods of bioinformatics, including hierarchical clustering, gene enrichment, KEGG analysis and correlational analyses.
The effects of EGCG on the expression profile of some interesting genes were confirmed by qPCR. Among the EGCG-regulated genes, we identified several modules and numerous significant genes that were associated with cell cycle, cell proliferation and inflammation-related functions, which then identified the transcription factor E2F2 as highly up-regulated and strongly correlated with the inflammation factor IL Our results confirmed that E2F2 mRNA level increased and that the IL mRNA level was lowered with EGCG treatments by qPCR at PD 45 of WI cells.
p53 is a critical and complex player in the regulation of apoptosis, cell cycle, senescence and longevity. The increasing evidence demonstrates that interleukin IL is a proinflammatory cytokine, inducing IL-1α, IL-1β, IL-6, IL-8, and tumor necrosis factor TNF -α via nuclear factor NF -κB and p38MAPK signal transduction pathways.
In addition, the effects of ROS, inflammatory factors levels, and p53, Rb, p-Rb, E2F2, IL and TNF-α expressions were obviously changed by EGCG after treated with p53 siRNA or pEXP-RB-Mam-EGFP-p53 in WI fibroblasts. View PDF Version Previous Article Next Article.
DOI: Received 4th May , Accepted 8th August Abstract Increased levels of oxidative stress and inflammation are the underlying mechanisms behind the aging process and age-related diseases.
The effects of EGCG 0, 25, 50, , , , and μM for 24, 48 and 72 h with the MTT assay.
Appetite suppressant foods of Pharmacology, Pharmaceutical College aigng China Medical University. Aginb aging mice model EGCG and aging induced EGCG and aging subcutaneous EGCG and aging. once agimg for 4 weeks after Agign D -gal injection. The water maze test was used to evaluate the learning EGC memory function of mice. The activities of total superoxide dismutase T-SOD and glutathione peroxidase GSH-Px and the contents of malondialdehyde MDA in the hippocampus were measured using different biochemical kits to estimate the changes in the antioxidative ability of mice. TdT-mediated dUTP-biotin nick end labeling TUNEL staining method was used to detect neuronal apoptosis, and the activation and expression of proapoptotic protein caspase-3 in the hippocampus were observed and analyzed using immunohistochemical staining and the Western blot method to evaluate apoptosis in the brain. Thank you for EGCG and aging nature. You are using a browser version with limited support for EGCG and aging. To ane EGCG and aging best experience, we recommend snd use a Beta-alanine and muscle carnosine levels up to date browser or turn off aginv mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. However, as a water-soluble component, how EGCG exerts its anti-AD effects in the brain was not elucidated. In the present study, we investigated the anti-AD mechanisms of EGCG in natural aging rats with cognitive impairments CIs assessed using Morris water maze. The expression of β-amyloid Aβ 1—42 in the brain was detected with immunohistochemical staining.
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