Aging Model Group Research Articles

Mechanism of tea polyphenols improving the sarcopenia in the aged type 2 diabetes model rats via mitochondrial quality control

To explore whether tea polyphenols(TP) improve sarcopenia in the aged type 2 diabetes(T2DM)model rats via mitochondrial quality control(MQC). A total of 55 2-month-old male SD rats were randomly divided into the control group(n=10), the aged model group(aged, n=10) and the aging T2DM model group(n=35). The aging T2DM model group rats were fed with high-sugar and high-fat diet and intraperitoneally injected with 50 mg/kg D-galactose daily. After 4 weeks, the aging T2DM model group rats were given a single intraperitoneal injection of 30 mg/kg streptozotocin(STZ). After STZ injection for 2 weeks, fasting blood glucose(FBG) ≥ 16.7 mmol/L was defined as successful T2DM model. When the model was successfully induced, the 30 model rats were randomly divided into aged T2DM group(Mod), 300 mg/kg TP teatment group(TP) and 3 mg/kg rosiglitazone treatment group(RSG) according to FBG, with 10 rats in each group. Each group was treated with 50 mg/kg D-galactose to induce senescence and fed with high glucose and fat for 8 weeks. Western blot was used to detect the expression of P53 protein in gastnemius muscle tissue of the model group at the end of the experiment, which was higher than that of the control group, indicating that the aging T2DM model was successfully established. FBG was detected by the blood glucose meter, gastnemius muscle relative weights was calculated, the microstructure of mitochondria of gastnemius muscle was observed by transmission electron microscope(TEM), the expression of mitochondrial biosynthesis-related proteins PGC-1α, mitochondrial dynamics-related proteins(OPA1, DRP1) and mitochondrial autophagy-related proteins(P62, LC3) in gastnemius muscle were detected by western blot. Compared with the control group, the level of FBG and the expression of P53 in the Mod group were increased(P<0.01). The gastnemius muscle relative weights, the expression level of PGC-1α, OPA1 and the ratio of LC3II/LC3I were decreased(P<0.01). The expression level of P62 and DRP1 were significantly increased(P<0.01). The number of mitochondria decreased, the volume decreased and a large number of vacuolization, and there were no obvious autophagolysosomes and fission and fusion. After 8 weeks, compared with the Mod group, the number of mitochondria in the gastrocnemius of TP and RSG groups, vacuolization, fission and fusion were improved, and the autophagolysosomes was significantly increased. The expression levels of P53, DRP1 and P62, the level of FBG in the TP group were significantly decreased(P<0.01, P<0.05). The expression levels of OPA1 and PGC-1α, the ratios of LC3II/LC3I and gastnemius muscle relative weights were significantly increased(P<0.05, P<0.01). TP can improve the sarcopenia in the aged T2DM model rats, and its mechanism is related to the regulation of mitochondrial quality control.

Targeting microbiota–immune–synaptic plasticity to explore the effect of tea polyphenols on improving memory in the aged type 2 diabetic rat model

ABSTRACT Objectives The study aimed to explore whether TP could improve memory in the aged type 2 diabetic rat model by regulating microbiota-immune-synaptic plasticity axis. Methods The experiment was divided into two parts. Firstly, to investigate the effects of TP on the physiopathology of the aged T2DM model rats, rats were randomly divided into the Normal control group, the aged group, the Aged T2DM model group, the TP 75, 150, 300 mg/kg groups, the 150 mg/kg Piracetam group and the 3 mg/kg Rosiglitazone group. Then, to further verify whether TP improved memory in aged T2DM rat model by regulating intestinal flora, the fecal microbiota transplantation (FMT) from the rats in the 300 mg/kg TP group into the rats in the aged T2DM model group was carried out. Effects on gut microbiota, colonic integrity (epithelial tight junction proteins), and endotoxemia (serum LPS) were examined, along with synaptic structure, synaptic plasticity-related structural proteins and inflammation signaling of the hippocampus in our study. Results Our results demonstrated that TP alleviated memory impairments in the aged T2DM rat model. The specific outcomes were as follows: TP 300 mg/kg corrected the gut dysbacteriosis, alleviated intestinal permeability reduction and peripheral/central inflammation, inhibited the TLR4/NF-κB signaling pathway. Meanwhile, TP improved the synaptic plasticity in the hippocampus of the aged T2DM model rats, whose expressions of SYN, PSD 95, NMDAR1 and GluR1 in hippocampus were significantly up-regulated. Surprisingly, rats of the FMT group displayed the same changes. Discussion TP improves the memory in aged T2DM rat model. The mechanism may be related to the alteration of gut flora, which can inhibit hippocampal TLR4/NF-κB signaling to attenuate neuroinflammation, then improve synaptic plasticity. The study proposes that TP interventions aimed at manipulating the gut microbiota may hold great potential as an effective approach for preventing and treating this disease.

Dapagliflozin mitigates oxidative stress, inflammatory, and histopathological markers of aging in mice.

Aging, a complex physiological process affecting all living things, is a major area of research, particularly focused on interventions to slow its progression. This study assessed the antiaging efficacy of dapagliflozin (DAPA) on various aging-related parameters in a mouse model artificially induced to age. Forty male Swiss albino mice were randomly divided into four groups of ten animals each. The control group (Group I) received normal saline. The aging model group (Group II) was administered D-galactose orally at 500mg/kg to induce aging. Following the aging induction, the positive control group received Vitamin C supplementation (Group III), while the DAPA group (Group IV) was treated with dapagliflozin. The inflammatory mediators (TNF-α and IL-1β) showed similar patterns of change. No statistically significant difference was observed between groups III and IV. Both groups had significantly lower values compared to GII, while it was significantly higher compared to GI. Glutathione peroxidase (GSH-Px) showed no statistically significant difference between groups GIII and GIV, but it was higher in GIII compared to GII and significantly lower in GIII compared to GI. The study demonstrated that dapagliflozin exerts a beneficial impact on many indicators of aging in mice. The intervention resulted in a reduction in hypertrophy in cardiomyocytes, an enhancement in skin vitality, a decrease in the presence of inflammatory mediators, and an improvement in the efficacy of antioxidants.

Cellular and molecular mechanisms of highly active mesenchymal stem cells in the treatment of senescence of rhesus monkey ovary

BackgroundRecent studies have shown that umbilical cord mesenchymal stem cells have an anti-aging effect in ovaries, but the cellular and molecular mechanisms of HA-MSC ovarian anti-aging remain to be studied. Therefore, we conducted a 10X Genomics single-nucleus transcriptome sequencing experiment on the ovaries of macaque monkeys after HA-MSC treatment.MethodsThe results of cell subgroup classification were visualized by 10X Genomics single nuclear transcriptome sequencing. The aging model of hGCs was established, and the migration ability of the cells was determined after coculture of HA-MSCs and aging hGCs. The genes screened by single nuclear transcriptional sequencing were verified in vitro by qPCR.ResultsCompared with the aging model group, the number of cell receptor pairs in each subgroup of the HA-MSC-treated group increased overall. Treatment with 200 μmol/L H2O2 for 48 h was used as the optimum condition for the induction of hGC senescence. After coculture of noncontact HA-MSCs with senescent hGCs, it was found that HA-MSCs can reverse the cell structure, proliferation ability, senescence condition, expression level of senescence-related genes, and expression level of key genes regulating the senescence pathway in normal hGCs.ConclusionsHA-MSC therapy can improve the tissue structure and secretion function of the ovary through multiple cellular and molecular mechanisms to resist ovarian aging. In vitro validation experiments further supported the results of single-cell sequencing, which provides evidence supporting a new option for stem cell treatment of ovarian senescence.

Serum metabolomics study of anti‐aging mechanisms of different processed Schisandra chinensis fructus products

AbstractThis study aimed to investigate the anti‐aging mechanism of raw and various processed Schisandrae chinensis fructus (SF) products by examining differences in serum metabolites in D‐galactose (D‐gal)‐induced aging rats. The study provides a metabolomic basis for SF as a tonic. The ultra‐high‐performance liquid chromatography‐Q‐time of flight‐tandem mass spectrometry technique was employed for serum metabolomic analysis of the anti‐aging effects of differently processed SF products. Multivariate statistical analysis, MetaboAnalyst, and Human Metabolome Database were utilized for pattern recognition and identification of characteristic metabolites. Enzyme‐linked immunosorbent assay results revealed significant differences between the aging model group and the blank group (p < 0.01). Treatment with various processed SF products significantly improved related indicators in aging rats (p < 0.05, p < 0.01). Arginine and seven other metabolites exhibited direct effects on aging. Wine‐processed Schisandrae (WS) treatment adjusted these biomarkers in aging rats to normal levels. WS significantly delayed D‐gal‐induced aging in rats by modulating endogenous biomarkers in relevant metabolic pathways, providing a scientific basis for its enhanced suitability as a tonic from a metabolomic perspective.

A study on the delayed effect of tilapia skin collagen on skin aging for mice and its possible mechanism.

Study the possible mechanism and delayed effect of tilapia skin collagen on skin aging for mice. Kunming (KM) mice were randomly divided into the aging model group, the normal group, the positive control group (vitamin E) and the low, medium, high dose tilapia skin collagen groups (2.0, 4.0, 8.0 mg/g). The normal group was only injected with saline at the back and the neck. The other groups were injected subcutaneously with 5% D-galactose and ultraviolet light jointly to establish the aging model. After modeling, the positive control group was treated with a dose of 10% vitamin E once a day, and the low, medium, high dose tilapia skin collagen group was separately applied 2.0, 4.0, 8.0 mg/g of tilapia skin collagen for 40 days. The changes of skin tissue morphology, water content, hydroxyproline (Hyp) content, and superoxide dismutase (SOD) activity in mice were studied at the day 10, 20, 30, 40, 50. Compared with the normal group, the skin of mice in the aging model group was thinner, looser, and the skin moisture content, Hyp content, SOD activity were all decreased. For mice of the low, medium, high dose tilapia skin collagen group, the thickness of dermis increased, possessing close arrangement, and the moisture content, Hyp content, SOD activity were up-regulated significantly, which effectively alleviated the aging process of skin. The dose of tilapia skin collagen was directly proportional to the anti-aging effect. Tilapia skin collagen has an obvious effect on improving skin aging.

Phillyrin Ameliorates Oxidative Stress in D-Galactose-Induced Senescence in the Brain of Mice by Regulating the Nrf2/ HO-1 Signaling Pathway

Objective To investigate the effects of phillyrin on D-galactose (D-gal)-induced aging in the brain of mice and mechanism. Methods Institute of Cancer Research mice were intraperitoneally injected with D-gal 150 mg/kg to induce the aging model, and the mice were treated with phillyrin 5, 15, and 45 mg/kg once a day for 8 weeks. Results The memory impairment induced by D-gal in brain aging was ameliorated by phillyrin treatment, and the oxidative stress in the aging brain and serum was inhibited, as evidenced by increased superoxide dismutase, glutathione peroxidase enzyme activities, and decreased malondialdehyde levels. Additionally, the hippocampus damage has also been well improved by phillyrin. Moreover, the protein expressions of nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NADPH quinone oxidoreductase 1 (NQO1) were markedly up-regulated and the expression of Keap-1 was down-regulated in the phillyrin group than that in the aging model group. Conclusion These findings suggest that phillyrin is effective in the prevention of age-related memory impairment, and the attenuation oxidative stress by activating the Nrf2/HO-1 signaling pathway in the hippocampus may be one of the mechanisms.

Effects of Rosa roxburghii Tratt glycosides and quercetin on D-galactose-induced aging mice model.

To investigate the effects of RRT (Rosa roxburghii Tratt) glucosides and quercetin on oxidative stress and chronic inflammation in D-galactose-induced aging mice, 90 mice (8 weeks old) were randomly divided into the normal group (NC), aging model group (D-gal), isoquercitrin group (D-gal+isoquercitrin), quercitrin group (D-gal+quercitrin), quercetin group (D-gal+quercetin) and positive control group (D-gal+Metformin). The aging model was established by subcutaneous injection of D-galactose (100 mg/kg). After 42 days of the administration, antioxidant and inflammatory indexes were measured, HE staining was used to investigate pathological changes in liver and brain tissue, and Western blot was used to determine the protein abundance of nuclear factor E2-related factor (Nrf2) and heme oxygenase (HO-1) in the brain. The results showed that, when compared to the NC group, the D-gal group had a significantly lower brain, liver, kidney, and spleen indexes; the contents of MDA, L-1β, IL-6, and TNF-α in serum, liver, and brain were significantly higher, but the levels of CAT, SOD, and GSH-Px were significantly lower. Isoquercitrin, quercitrin, and quercetin significantly increased organ indexes and activities of CAT, SOD, and GSH-Px while decreasing MDA, IL-1β, IL-6, and TNF-α levels in serum, liver, and brain tissues compared to the D-gal group. The morphological changes in the brain and liver tissue were significantly restored by glycosides and quercetin, as observed in HE staining. Furthermore, Western blot results revealed that glycosides and quercetin increased the protein levels of Nrf2, HO-1, and NQO1. Finally, the antioxidant and anti-inflammatory effects of RRT glycoside and quercetin in aging may be attributed to an activated Nrf2/HO-1 signaling pathway. PRACTICAL APPLICATIONS: Aging is characterized by physical changes and dysfunction of numerous biological systems caused by a variety of factors. The oxidative stress and inflammatory effects of RRT glycosides and quercetin on D-galactose-induced aging mice were investigated in this study. RRT glycosides and quercetin were found to protect organ atrophy, liver, and brain tissue in aging mice by regulating oxidative stress and chronic inflammation. It served as the theoretical foundation for the investigation of Rosa roxburghii Tratt as a health product and pharmaceutical raw material.

Effects of astragaloside IV on delaying kidney aging and its mechanisms

To investigate the mechanisms of Astragaloside Ⅳ on inhibiting apoptosis and delaying kidney aging in rats by regulating SIRT1/p53 signaling pathway. The aging model was established by subcutaneous injection of D-galactose 200 mg/(kg·d). SPF-grade healthy male SD rats were randomly divided into 4 groups: normal control group (intragastric infusion of 5 ml/(kg·d) normal saline), aging model group (intragastric infusion of 5 ml/(kg·d) normal saline), Astragaloside IV group (intragastric infusion of 40 mg/(kg·d) Astragaloside IV),and SRT1720 group( intragastric infusion of 20 mg/(kg·d) SRT1720), with 10 rats in each group. After 8 weeks, the serum samples of rats were collected to detect the levels of renal function (creatinine and urea nitrogen) and senescent associated secretory phenotype (TGF-β and IL-6) by ELISA. The renal tissues of rats were obtained for HE and Masson staining. The protein and mRNA expressions of SIRT1, p53, Bcl-2, Bax, p21 and pRb were detected by Western blot and RT-PCR. Serum creatinine and urea nitrogen levels in the aging model group were higher than those in the normal group, but there was no significant difference in each group (P＞0.05). The serum levels of TGF-β and IL-6 in the aging model group were higher than those in the normal group (P＜0.05), and which in the Astragaloside IV group and SRT1720 group were lower than those in the model group (P＜0.05). There was no significant differences between Astragaloside IV group and SRT1720 group (P＞0.05). The results of pathological staining of renal tissues showed that, compared with the normal group, the renal tubules dilated, local atrophy, infiltration of inflammatory cells and proliferation of collagen fibers were observed in the aging model group. Compared with the aging model group, the pathological changes were alleviated in Astragaloside IV group and SRT1720 group. The results of Western blot and RT-PCR showed that, compared with the normal group, the protein and mRNA expressions of SIRT1 and pRb in the renal tissue of the aging group were decreased, the protein expression of Bcl-2 was decreased(P＜0.05), and the protein and mRNA expressions of p53 and p21 were increased, the protein expression of Bax was increased(P＜0.05). Compared with the aging group, Astragaloside IV and SRT1720 improved the above-mentioned indexes (P＜0.05). Astragaloside IV can delay kidney aging by regulating the SIRT1/p53 signaling pathway.

Effects Of Aerobic Exercise On Synaptic Plasticity And PKA Expression In Hippocampus Of Aging Rats

PURPOSE: To investigate the Effects of aerobic exercise on synaptic plasticity and PKA expression in hippocampus of aging rats. METHODS: Sixty male SD rats were divided into 3 group at random: saline control group(SC), aging model group(S), aerobic exercise intervention on aging group(SE). Aging model was established by injecting low galactose via peritoneal, 100 mg / kg, once a day for 6 weeks in S and SE. And S were injected the same dosage of saline. D-gal were injected in S and SE and were simultaneously administered for a 6-week swimming exercise intervention, 6 days a week for 1 hour a day. And the general state of rats was observed weekly. At the end of modeling and swimming, Morris water maze was used to evaluate the spatial learning and memory ability. HE staining was used to observe Morphological changes of Hippocampus. The expression of PKA was tested by western blotting. The expression of BDNF and SYN in Hippocampus was tested by immunofluorescence. The experimental data was reported as mean ± SE. level of significance was set at α = 0.05. RESULTS: 1) Compared with SC and SE, S showed obvious signs of aging, such as loss of weight, decrease of activity, loss hair and neurons significantly reducing, the cell morphology was incomplete and the chromatin was unevenly colored. 2) The Morris water maze test was showed that: Compared with SC, the escape latency of S was significantly increased (P < 0.01); the number of crossing the platform was significantly reduced (P < 0.01). Compared with S, the escape latency of SE was significantly decreased (P < 0.05), and the number of crossing the platform was significantly increased (P < 0.01). 3) Compared with S, the expression of PKA was significantly increased in SC and SE (1.30 ± 0.03 vs. 0.77 ± 0.07, P < 0.01; 1.22 ± 0.11 vs. 0.77 ± 0.07, P < 0.05). 4) Compared to S, the immunofluorescence density values of BDNF and SYN significantly increasing was observed in SC and SE (25.52 ± 1.34 vs. 16.83 ± 1.30, P < 0.01; 23.15 ± 1.26 vs. 16.83 ± 1.30, P < 0.05); (53.85 ± 6.14 vs. 25.68 ± 1.36, P < 0.01; 51.18 ± 1.26 vs. 25.68 ± 1.36, P < 0.01). CONCLUSIONS: 6 weeks of aerobic exercise effectively reverses brain injury and learning and memory impairment in aging rats. The mechanism may be related to significantly up-regulate the expression of PKA in hippocampus to promote synaptic plasticity and improve learning and memory ability.

Corn embryo ameliorates cognitive dysfunction and anxiety-like behaviors in D-galactose-induced aging rats via attenuating oxidative stress, apoptosis and up-regulating neurotrophic factors

Aging is the primary cause of neurodegenerative diseases, which are mainly characterized by cognitive decline and neuropsychiatric symptoms. Corn embryo, an important component of corn kernels, contains plenty of essential nutrients and bioactive compounds. However, corn embryo is often removed in the process of refining corn. To reveal potential biological benefits of corn embryo, the present study investigated the intervention effects of corn embryo on age-related cognitive decline and neuropsychiatric symptoms. Ninety male Wistar rats were randomly divided into six groups: Control, Corn embryo, Aging model, Low-, Medium- and High-dose intervention group. Aging models induced by an intraperitoneal injection of 60 mg/kg D-galactose plus a gavage of 200 mg/kg aluminum chloride were intervened with a gavage of 0.3, 0.6 or 1 g/kg corn embryo while the Control and Corn embryo groups received saline and 0.6 g/kg corn embryo respectively. Morris water maze and open field test were performed to assess cognitive abilities and anxiety-like behaviors. Brain biochemical parameters including the malondialdehyde, glutathione, glutathione sulfhydryl transferase and γ-glutamylcysteine synthetase were detected to evaluate oxidative stress levels. The mRNA expression of brain-derived neurotrophic factor was determined to estimate neurotrophic factor levels. Besides, histopathological alterations were visualized by hematoxylin-eosin staining and neuronal apoptosis levels were measured by the immunohistochemical staining of Bax and Bcl-2. Ultimately, the mimetic aging rats showed significant cognitive impairment (n = 15, P < 0.01) and anxiety-like behaviors (n = 15, P < 0.01), increased oxidative stress (n = 5, P < 0.001), neurodegeneration (n = 5, P < 0.001) and apoptosis (n = 5, P < 0.01) and reduced neurotrophic factors (n = 5, P = 0.074) in the brain. However, corn embryo effectively prevented the above undesirable neurobehavioral alterations via attenuating oxidative stress (n = 5, P < 0.01), neurodegeneration (n = 5, P < 0.001) and apoptosis (n = 5, P < 0.01) and increasing the levels of neurotrophic factors (n = 5, P < 0.001), suggesting its strong neuroprotective effects.

Peanut meal extract fermented with Bacillus natto attenuates physiological and behavioral deficits in a D-galactose-induced aging rat model.

Our previous studies have shown that the nutritional properties of peanut meal after fermentation are markedly improved. In this study, in order to facilitate the further utilization of peanut meal, we investigated the effects of its fermentation extract by Bacillus natto (FE) on cognitive ability, antioxidant activity of brain, and protein expression of hippocampus of aging rats induced by D-galactose. Seventy-two female SD rats aged 4-5 months were randomly divided into six groups: normal control group (N), aging model group (M), FE low-dose group (FL), FE medium-dose group (FM), FE high-dose group (FH) and vitamin E positive control group (Y). Morris water maze (MWM) test was performed to evaluate their effects on learning and memory ability in aging rats. SOD activity and malondialdehyde (MDA) content of brain, HE staining and the expression of γ-aminobutyric acid receptor 1 (GABABR1) and N-methyl-D-aspartic acid 2B receptor (NMDAR2B) in the hippocampus of rats were measured. The results show that FE supplementation can effectively alleviate the decrease of thymus index induced by aging, decrease the escape latency of MWM by 66.06%, brain MDA by 28.04%, hippocampus GABABR1 expression by 7.98%, and increase brain SOD by 63.54% in aging model rats. This study provides evidence for its anti-aging effects and is a research basis for potential nutritional benefits of underutilized food by-products.

Tea polyphenols ameliorates memory decline in aging model rats by inhibiting brain TLR4/NF-κB inflammatory signaling pathway caused by intestinal flora dysbiosis.

Tea is a rich source of pharmacologically active molecules that has been suggested to provide a variety of health benefits. However, its mechanism of action in aging-related intestinal flora dysbiosis mediated neuroinflammation is still unclear. This study aimed to explore whether tea polyphenols (TP) can improve memory by regulating intestinal flora mediated neuroinflammation in aging model rats. Ovariectomy (OVX) combined with D-galactose injection was used to establish aging rats related to menopause. The rats were divided into Sham control group, Aging model group, TP 75mg/kg, 150mg/kg, 300mg/kg groups and VE group. After 12weeks of intervention, the shuttle box test and Y maze test were used to check the memory of rats. The composition of intestinal flora was assessed by 16S rRNA sequencing technology. HE staining and ELISA were used to detect intestinal epithelial morphology and permeability, respectively. TLR4/NF-κB inflammation pathway related indicators were investigated by western blot, and the microglia activation in rat hippocampal tissue was checked by immunofluorescence. In the shuttle box test and the Y maze test, compared with the Sham control group, the memory of Aging model rats was significantly declined. It was observed that the intestinal flora of Aging model rats was dysbiosis, the permeability of the intestinal epithelium was increased. Further experimental results showed that the expression of TLR4/NF-κB inflammatory pathway related proteins in the hippocampus were increased, and the excessive activation of microglia was observed. The beneficial effects of TP intervention have been found to prevent memory decline and significantly improve brain inflammation induced by intestinal flora dysbiosis, and TP 300mg/kg showed a more obvious advantage than TP 75mg/kg. TP 300mg/kg can significantly improve the behavior of rats, improve the composition and diversity of the intestinal flora, and the shape and function of the intestinal epithelium. By reversing the increased expression levels of TLR4, IRAK, p-IκBα and nuclear NF-κB p65 proteins in the hippocampus of Aging model rats, the activation of microglia in the CA1, CA3 and Dentate gyrus (DG) sub-regions of the hippocampus can be inhibited. TP inhibits the brain TLR4/NF-κB inflammatory signal pathway caused by the dysbiosis of intestinal flora, which may be one of the mechanisms to improve the memory decline in aging model rats.

Influences of 6-furfuryloaminopurine on Peripheral T Lymphocyte Subpopulations and Apoptosis of Thymus Lymphocytes of Aging Rats

Background: 6-furfuryloaminopurine (KT) is the first compound to be identified as a cytokinin. Despite that there are many studies related to KT but the mechanism of KT in resisting immunosenescence remains unclear. The objective of this study is to investigate the influences of KT on the immunity of thymus in rats by detecting the apoptosis and the proliferation index (PI).Methods: We firstly established an aging rat model by subcutaneously injecting D- galactose (D-gal, 125mg/kg•BW) in the dorsal neck of Sprague Daly rats (SD rats); then the rats were divided into KT treatment groups (three groups for different doses of KT), aging model group (without KT treatment) and young control group. The rats in KT treatment groups were treated with different-dose KT and the key indices including the changes of the number of CD3+, CD4+ and CD8+ T lymphocyte subpopulations in peripheral blood, the apoptosis of thymus lymphocytes. Result: KT could increase the number of the peripheral CD3+, CD4+ and CD8+ T lymphocytes of the aging rats while decreased the apoptotic rate of thymocytes and increased PI Index.

Effects of resveratrol combined with soy isoflavones on apoptosis induced by oxidative stress in hippocampus of aging model rats

To investigate the effect of resveratrol(Res) combined with soy isoflavones(SIF) on apoptosisinduced by oxidative stress in hippocampus in aging model rats. Sixty female SD rats were randomly divided into the Sham control group, aging model group, Res treatment group, SIF treatment group, Res combined with SIF treatment group and estrogen replacement therapy group(ERT group). Rats with aging were induced by bilateral ovariectomy combined with intraperitoneal injection of D-galactose. TUNEL and transmission electron microscopy were used to observe apoptosis and ultrastructural changes of mitochondrion in hippocampus, respectively. The activities of superoxide dismutase(SOD), catalase(CAT), glutathione peroxidase(GSH-Px) and content of Malonaldehyde(MDA) were detected in the hippocampal homogenate. The protein expressions of cytochrome C oxidase(COX) Ⅰ, Bcl-2 associated X protein(Bax)、B-cell leukemia/lymphoma 2(Bcl-2) and cytochrome C were detected by Western blot. Compared with the Sham control group, the number of TUNEL-positive cells and the apoptotic index(AI) in the model group increased. Marked increase of mitochondrial swelling and vacuolation, decrease of mitochondrial integrity were also observed in the model group. Additionally, the levels of SOD, CAT and GSH-Px were decreased and the level of MDA was increased in the model group in the hippocampus, Bax and cytochrome C protein expression increased, and the COX Ⅰ protein expression and the ratio of Bcl-2/Bax decreased(P&lt;0. 05). In compared with the model group, the number of TUNEL-positive cells and AI significantly decreased, mitochondrial integrity improved in all of the treatment groups, the COX Ⅰ protein expression significantly up-regulated, Bax and cytochrome C protein expression down-regulated, and the protein expression ratio of Bcl-2/Bax increased(P&lt;0. 05 or P&lt;0. 01). Compared with the Res alone and SIF alone treatment group, Res combined SIF treatment decreased the AI and Bax, cytochrome C protein expression, moreover, increased the mitochondrial integrity rate, COX Ⅰ and Bcl-2/Bax protein expression ratio(P&lt;0. 05). There was no statistically significant difference in Bcl-2 protein expression among all the groups(P&gt;0. 05). Res and SIF alone and in combination decreased apoptosisinduced by oxidative stress in hippocampus of aging model rats, and beneficial effect in the Res combined SIF treatment group is more significant than that in the alone administration. Improving the antioxidant capacity, increasing the protein expressions of COX Ⅰ andthe ratio of Bcl-2 and Bax, and inhibiting the release of cytochrome C may be the mechanisms by which Res and SIF improve apoptosis in aging rats.

The Effects Of Aerobic Exercise On Free Radical Expression In Hippocampus Of Aging Rats

PURPOSE: The effects of aerobic exercise on free radical expression in hippocampus of aging rats. METHODS: Eighty male SD rats were divided into 4 groups(n=20) at random: control group(C), D-galactose aging model group(A), pre-aging aerobic exercise intervention group (S1), aerobic exercise intervention on aging group (S2). Following a 1 week acclimation to laboratory conditions, D-gal were injected in D, S1 and S2 groups rat’s peritoneal to make aging model, the injection dosage via body weight of the rats, 100mg / kg, once a day for 6 weeks. Group C were injected the same dosage of saline. We did 1 hour per day, six times per week’s swimming training seprately before and during the injection of D-gal administration in group S1 and S2. At the end of modeling and swimming, Morris water maze was used to evaluate the spatial learning and memory function of rats; the activities of SOD, GSH PX and MDA expression in hippocampus of rats in each group were measured. All data were processed with one-way ANOVA, level of significance was set at α=0.05. RESULTS: (1) Compared with group C, group A had obvious symptoms of aging. (2)Water maze navigation trial showed that group C, S1 and S2 formed stable spatial learning and memory function on day 3 but that of group A formed on day 4; in the space exploration experiment group C reached the destination for most times, the percentage of the original site quadrant of group C was the highest, and there were significant differences between other groups (P<0.01); group S2 followed but group A and S1 were relatively low. (3) Morphological observation showed that the hippocampal neurons of rats in group A appeared derangement, deepening of cell staining and cytoplasmic edema. (4) The activities of SOD and GSH-Px in the hippocampus of group S2 were similar to group C, and the activities of group A and S1 were significantly lower than group C (P < 0.01); the expression levels of MDA were significantly down-regulated in group C, group S2 followed, and all significantly lower than those in group A and S1(P<0.05). CONCLUSIONS:Swimming in the process of aging can improve and maintain the spatial learning and memory function of brain and delay brain aging. The mechanism may be related to reduce free radical expression’s regulatio.

Effects of resveratrol and soy isoflavones on learning and memory ability and expression of glucose transporter in aging model rats

To investigate the effects of resveratrol combined with soy isoflavones on avoidance memory, number of neuron-specific nuclear protein(NeuN) positive cells and expressions of glucose transporter(GLUT)1 and GLUT3 in hippocampus of aging model rats. A total of 60 female SD rats were randomly divided into 6 groups including sham control group, aging model group, 80 mg/kg resveratrol group, 160 mg/kg soy isoflavones group, 80 mg/kg resveratrol +160 mg/kg soy isoflavones group, 0. 8 mg/kg estradiol valerate group. The aging model rats was induced by ovariectomy combined with intraperitoneal injection of 100 mg/kg D-galactose. Intragastric administration was performed once a day for 12 weeks. The avoidance task was measured by the shuttle box test. The NeuN expression were measured by the immunofluorescence. The genes and proteins expression of GLUT1 and GLUT3 in rat hippocampus were detected by real-time PCR and Western blot, respectively. Compared with the sham control group, the avoidance latency in the aging model group was prolonged, and the active avoidance response rate and the total avoidance response rate were decreased. The number of NeuN positive cells decreased and the expression levels of GLUT1 and GLUT3 genes and proteins were decreased(P&lt;0. 05). Compared with the aging model group, the escape latency significantly declined(P&lt;0. 01), but the rates of active avoidance response and total avoidance response increased, the number of NeuN positive cells increased significantly, the expression levels of GLUT1 and GLUT3 genes and proteins up-regulated in the rats of the three intervention groups(P&lt;0. 05 or P&lt;0. 01). Compared with the soy isoflavones group, the active avoidance response rate was increased in the combined group(P&lt;0. 05). In comparison with those for the resveratrol group, the avoidance latency was shortened and the active avoidance response rate was increased, the number of NeuN positive cells and the expression levels of GLUT3 gene and protein were significantly increased in the combined group(P&lt;0. 05). There was no significant difference between the combined intervention group and the estradiol valerate group(P&gt;0. 05). Resveratrol and soy isoflavones alone and in combination can improve the learning and memory ability of aging rat models. The mechanism may be related to up-regulating the expression of GLUT1 and GLUT3 genes and proteins in the hippocampus, promoting the transmembrane transport of glucose and reducing neuronal loss.

Effect of saponins extracted from Panax japonicas on inhibiting myocardial fibrosis by TGF-β1/Smad3 signaling pathway in aging rats

To investigate the amelioration effect of saponins extracted from Panax japonicas (SPJ) on myocardial fibrosis in natural aging rats and its mechanisms, male SD rats aged 18 months were randomly divided into 3 groups (aging model group, low-dose SPJ group and high-dose SPJ group), with 10 rats in each group. SPJ groups were given SPJ at different doses (10, 60 mg·kg⁻¹·d⁻¹) consecutively for 6 months, meanwhile, aging model group was treated with the equal volume of saline for 6 months until 24 months old. Another 10 rats aged 6 month were used as young control group. The changes of myocardial morphological were observed by haematoxylin-eosin (HE) staining. Masson staining was used to observe the changes of collagen deposition in rat hearts. RT-PCR was used to detect the mRNA expression levels of myofibroblast marker α-SMA, collagen-related protein COL1α2, COL3α1 and matrix metalloproteinase MMP2, MMP9. Western blot was used to test the changes of the protein expressions of TGF-β1, p-Smad3, IL-1β and TNF-α in heart tissues. SPJ can effectively improve the arrangement of myocardial fibers, decrease inflammatory infiltration and reduce collagen deposition in aging rats. SPJ can effectively down-regulate the mRNA expression levels of COL1α2, COL3α1, α-SMA, MMP9, MMP2 and inhibit the protein expressions of TGF-β1, p-Smad3, TNF-α, IL-1β in the natural aging heart tissues. SPJ can effectively alleviate myocardial fibrosis in natural aging rats, and its mechanisms was related to the inhibition of the protein expressions of TGF-β1, p-Smad3 and the reduction of myocardial inflammation in rat hearts.

PO-216 The Effects of Aerobic Exercise on Spatial Learning and Memory and Expression of PDE-4 in Hippocampus of the Aging Rats

Objective To discuss the effect of aerobic exercise intervention before aging rats and on aging rats, the spatial learning and memory abilities and the expression of PDE-4 in hippocampus.&#x0D; Methods 64 male SD rats were divided into 4 groups at random (n=16): control group(group C), D-galactose aging model group (group A), Pre-aging aerobic exercise intervention group (group S1), Aerobic exercise intervention on aging group (group S2). After 6 weeks, each group was randomly divided into Morris water maze behavior training group (M group) and natural feeding group (N group), record as CM, AM, S1M, S2M, CN, AN, S1N, S2N. At the end of 7th week, all rats were killed and the cerebral cortex SOD, GSH-PX and MDA content were tested; The expression of PDE-4 gene in hippocampus was detected by Real-time PCR and Western blotting.&#x0D; Results 1) The general state: When compared to the rats in C group, which in A group show obvious symptoms of aging, such as lethargy, loss of appetite, slow, yellow curly hair color, even off signs and so on; but S2 group were similar to C group; S1 group were a little worse than S2 group. 2) HE staining: When compared to the rats in C group, the hippocampus neurons in A group were disordered, the cells staining were deepened, the cytoplasm were edema, most of the interstitial cells were loose, and other morphological structure in aging state;S2 group were similar to C group; S1 group were a little worse than S2 group.3) The free radical detection: Almost no difference in each corresponding M group and N group. The activities of the cerebral cortex SOD and GSH-PX in were consistent: C group and S2group were significantly or very significantly higher than others (P&lt;0.05/0.01); The cerebral cortex MDA content: C group was the lowest, S2 group followed, and all significantly lower than those in A group and S1 group (P&lt;0.05). 4)The Morris water maze test: the Positioning navigation experiment results showed that the spatial memory was preliminarily formed on the day 2, CM group, S1M group and S2M group formed stable spatial learning and memory on day 3,but that of AM group formed on day 4; The space exploration test results showed that the maximum number of times of through the site was CM group, the percentage of the original site quadrant of CM group was the highest, and there was a very significant difference with the other groups (P&lt;0.01); S2 group followed, but AM group and S1M were relatively low. 5)The results of Real-time PCR and Western blotting: When compared to the rats in C group, which in A group and S1group were very significantly higher(P&lt;0.01),but which in S2 group was very significantly lower (P&lt;0.01); When compared to the rats in A group, which in S2 group was very significantly lower (P&lt;0.01),but S1group were significantly higher(P&lt;0.01/0.05); When compared to the rats in S1 group, which in S2 group was very significantly lower (P&lt;0.01).&#x0D; Conclusions 1)Aerobic exercise can improve the antioxidant capacity of the brain, protect and repair the hippocampal neurons, change the morphological structure of hippocampal neurons, improve and maintain the brain's spatial learning and memory, and thus delay brain aging. 2)Aerobic exercise intervention can down-regulate the expression of PDE-4 gene, may directly activate the cAMP/PKA/CREB signal transduction pathway to promote the synthesis of some learning memory proteins, thereby improving the learning and memory ability of aging rats and delay brain aging. 3)The different periods of aerobic exercise on brain aging intervention were different. Aerobic exercise intervention in the aging process performed relatively well. Tip: sustained aerobic exercise need to better play its role.&#x0D;

Effects of artemisinin on learning and memory, inflammatory cytokines and monoamine neurotransmitters in aged mice

Objective To investigate whether the artermisinin has beneficial efficacy to improve the learning and memory in aged mice, as well as the possible mechanisms regarding the inflammatory cytokines and monoamlne neurotransmitters. Methods 30 aged mice(22 month old) were randomly divided into the aged mouse model control group(n=10), the artemisinin low dose group(artemisinin 0.1% in feed, n=10)and the artemisinin high dose group(artemisinin 0.3% in feed, n=10). Another 10 mice(2 month old) served as young mouse model control group. The artemisinin low dose group and the artemisinin high dose group fed artemisinin feed for 10 weeks. The aged mouse model control group and the young mouse model control group were fed standard feed.Morris water maze test was performed to assess learning and memory capacities for evaluation of the cognitive degree. Serum TNF-α and IL-6 were also detected by ELISA and dopamine, norepinephrine, serotonin in the brain were analyzed by HPLC. Results (1) Morris water maze test showed, the retention time of the aged mouse model control group was significantly longer than that of the young mouse model control group (P<0.05). The retention time of the artemisinin low dose group and the artemisinin high dose group was significantly shorter than that of the aged mouse model control group (P<0.05). In the ninth days of the reverse recessive platform experiment, the retention time of the artemisinin low dose group ((50.1±19.9) s) and the artemisinin high dose group ((43.2±17.6) s) was significantly shorter than that of the aged mouse model control group ((66.1±29.1)s, P<0.05). (2) Serum inflammatory factors test showed, the level of IL-6 and TNF-αin the artemisinin low dose group (IL-6 : (28.4±4.3) pg/ml, TNF-α: (51.8±8.2) pg/ml) and the artemisinin high dose group(IL-6 : (17.6±2.3) pg/ml, TNF-α: (38.6±12.5) pg/ml) were significantly lower than those in aged mouse model control group(IL-6 : (36.12±7.98)pg/ml), TNF-α : (67.32±10.27) pg/ml, P<0.05). (3) Neurotransmitter content test in the brain showed, the content of DA((19.96±3.89) mmol/ml) and 5-HT((5.73±0.93)mmol/ml) in low dose artemisinin group was higher than that in aged mouth model control group. The content of DA((26.13±5.66) mmol/ml), NE((16.31±2.69) mmol/ml) and 5-HT((8.03±1.93) mmol/ml) in high dose artemisinin group was higher than that in aged mouth model group(DA(13.96±3.89) mmol/ml, NE(8.73±2.16) mmol/ml, 5-HT (3.82±1.09)mmol/ml, all P<0.05). Conclusion Artemisinin can improve the ability of learning and memory in aged mice. The mechanism may be related to inhibiting the inflammation and promoting the level of neurotransmitters in the brain of aged mice. Key words: Artemisinin; The aged mice; Learning and memory; Inflammatory factor; Neurotransmitter