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Anti-Aging Effect of Adipose-Derived Stem Cells in a Mouse Model of Skin Aging Induced by D-Galactose  [PDF]
Shengchang Zhang, Ziqing Dong, Zhangsong Peng, Feng Lu
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0097573
Abstract: Introduction Glycation products accumulate during aging of slowly renewing tissue, including skin, and are suggested as an important mechanism underlying the skin aging process. Adipose-derived cells are widely used in the clinic to treat ischemic diseases and enhance wound healing. Interestingly, adipose-derived stem cells (ASCs) are also effective in anti-aging therapy, although the mechanism underlying their effects remains unknown. The purpose of the present study was to examine the anti-aging effect of ASCs in a D-galactose-induced aging animal model and to clarify the underlying mechanism. Materials and Methods Six-week-old nude mice were subcutaneously injected with D-gal daily for 8 weeks. Two weeks after completion of treatment, mice were randomized to receive subcutaneous injections of 106 green fluorescent protein (GFP)-expressing ASCs, aminoguanidine (AG) or phosphate-buffered saline (PBS). Control mice received no treatment. We examined tissue histology and determined the activity of senescence-associated molecular markers such as superoxide dismutase (SOD) and malondialdehyde (MDA). Results Transplanted ASCs were detectable for 14 days and their GFP signal disappeared at day 28 after injection. ASCs inhibited advanced glycation end product (AGE) levels in our animal model as well as increased the SOD level and decreased the MDA level, all of which act to reverse the aging phenotype in a similar way to AG, an inhibitor of AGE formation. Furthermore, ASCs released angiogenic factors in vivo such as vascular endothelial growth factor, suggesting a skin trophic effect. Conclusions These results demonstrate that ASCs may contribute to the regeneration of skin during aging. In addition, the data shows that ASCs provide a functional benefit by glycation suppression, antioxidation, and trophic effects in a mouse model of aging.
Polysaccharides from the Medicinal Mushroom Cordyceps taii Show Antioxidant and Immunoenhancing Activities in a D-Galactose-Induced Aging Mouse Model
Jian-Hui Xiao,Dai-Min Xiao,Dai-Xiong Chen,Yu Xiao,Zong-Qi Liang,Jian-Jiang Zhong
Evidence-Based Complementary and Alternative Medicine , 2012, DOI: 10.1155/2012/273435
Abstract: Cordyceps taii, an edible medicinal mushroom native to south China, is recognized as an unparalleled resource of healthy foods and drug discovery. In the present study, the antioxidant pharmacological properties of C. taii were systematically investigated. In vitro assays revealed the scavenging activities of the aqueous extract and polysaccharides of C. taii against various free radicals, that is, 1,1-diphenyl-2-picrylhydrazyl radical, hydroxyl radical, and superoxide anion radical. The EC50 values for superoxide anion-free radical ranged from 2.04 mg/mL to 2.49 mg/mL, which was at least 2.6-fold stronger than that of antioxidant thiourea. The polysaccharides also significantly enhanced the antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase) and markedly decreased the malondialdehyde production of lipid peroxidation in a D-galactose-induced aging mouse model. Interestingly, the immune function of the administration group was significantly boosted compared with the D-galactose-induced aging model group. Therefore, the C. taii polysaccharides possessed potent antioxidant activity closely associated with immune function enhancement and free radical scavenging. These findings suggest that the polysaccharides are a promising source of natural antioxidants and antiaging drugs. Consequently, a preliminary chemical investigation was performed using gas chromatography-mass spectroscopy and revealed that the polysaccharides studied were mainly composed of glucose, mannose, and galactose. Fourier-transform infrared spectra also showed characteristic polysaccharide absorption bands.
Purple Sweet Potato Color Ameliorates Cognition Deficits and Attenuates Oxidative Damage and Inflammation in Aging Mouse Brain Induced by D-Galactose
Qun Shan,Jun Lu,Yuanlin Zheng,Jing Li,Zhong Zhou,Bin Hu,Zifeng Zhang,Shaohua Fan,Zhen Mao,Yong-jian Wang,Daifu Ma
Journal of Biomedicine and Biotechnology , 2009, DOI: 10.1155/2009/564737
Abstract: Purple sweet potato color (PSPC), a naturally occurring anthocyanin, has a powerful antioxidant activity in vitro and in vivo. This study explores whether PSPC has the neuroprotective effect on the aging mouse brain induced by D-galactose (D-gal). The mice administrated with PSPC (100 mg/kg.day, 4 weeks, from 9th week) via oral gavage showed significantly improved behavior performance in the open field and passive avoidance test compared with D-gal-treated mice (500 mg/kg.day, 8 weeks). We further investigate the mechanism involved in neuroprotective effects of PSPC on mouse brain. Interestingly, we found, PSPC decreased the expression level of glial fibrillary acidic protein (GFAP), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), inhibited nuclear translocation of nuclear factor-kappaB (NF-B), increased the activity of copper/zinc superoxide dismutase (Cu/Zn-SOD) and catalase (CAT), and reduced the content of malondialdehyde (MDA), respectively. Our data suggested that PSPC attenuated D-gal-induced cognitive impairment partly via enhancing the antioxidant and anti-inflammatory capacity.
Rutin, a Flavonoid That Is a Main Component of Saussurea involucrata, Attenuates the Senescence Effect in D-Galactose Aging Mouse Model
Ying-Chen Yang,Hsueh-Yi Lin,Kang-Yi Su,Chien-Hsu Chen,Yung-Lung Yu,Chai-Ching Lin,Sung-Liang Yu,Hong-Young Yan,Kuo-Jung Su,Yi-Lin Sophia Chen
Evidence-Based Complementary and Alternative Medicine , 2012, DOI: 10.1155/2012/980276
Abstract: Saussurea involucrata (Kar. et Kir.), known as the snow lotus, grows in the Tian Shan and A’er Tai areas of China. It has recently been reported that the ethyl acetate extract of S. involucrata (SI-2) can inhibit proliferation and induce apoptosis in PC-3 human prostate cancer cells. This study investigated the protective effect of ethyl acetate extract of S. involucrata (SI-2) or rutin, a flavonoid extracted from ethyl acetate extract of S. involucrata (SI-2), on D-galactose- (D-gal-) induced brain injury in mice. Administering SI-2 or rutin (30 mg/kg/d and 30 mg/kg/d) for 6 weeks, concomitant with D-gal injection, significantly increased superoxide dismutase and glutathione peroxidase activities and decreased the MDA level in plasma. Furthermore, the result showed that the percentages of cleaved caspase-3 and PARP in the D-gal-treated mice were much higher than those in the control. Pretreatment using SI-2 or rutin decreased the expression of cyclooxygenase-2 via downregulation of NF-kappaB, resulting in a decrease in lipid peroxidation. Furthermore, our results also showed that oral administration of rutin to these mice significantly improved behavioral performance in a step-through passive avoidance task and these results suggest that SI-2 or rutin exerts potent antiaging effects on D-gal in mice via antioxidative mechanisms.
Effect of Liriope platyphylla total saponin on learning, memory and metabolites in aging mice induced by D-galactose
Tao JIANG,Lu-ping QIN
Zhong Xi Yi Jie He Xue Bao , 2007,
Abstract: Objective: To investigate the effects of Liriope platyphylla total saponin (LPTS) on learning, memory, neuromediators and metabolites in aging mice induced by D-galactose.Methods: Ninety Kunming mice were randomly divided into nine groups: normal saline (NS)-treated group, untreated group, high- (100 mg/kg), medium- (50 mg/kg) and low-dose (10 mg/kg) LPTS-treated groups, Shuxuening-treated group, jiaogulanosidi-treated group, flunarizine-treated group and vitamin E-treated group. The Kunming mice in the NS-treated group were administered with NS by intraperitoneal injection, while the aging mice in the other eight groups were administered with D-galactose by intraperitoneal injection. At the same time, the aging mice in different groups were fed with corresponding drugs for 42 days, and the aging items of the mice in different groups were measured, respectively.Results: LPTS could improve the memory of aging mice induced by D-galactose, promote its body weight, and increase the thymus and spleen indexes of the aging mice. LPTS could decrease the levels of MDA and lipofuscin, inhibit MAO activity and increase SOD activity and GSH-Px level.Conclusion: LPTS may improve the ability of learning and memory and delay aging.
Antioxidant Activity of Aspirin Eugenol Ester for Aging Model of Mice by D-Galactose
Jianyong Li,Yuanguang Yu,Yajun Yang,Xiwang Liu,Jiyu Zhang,Bing Li,Xuzheng Zhou,Jianrong Niu,Xiaojuan Wei
Journal of Animal and Veterinary Advances , 2012, DOI: 10.3923/javaa.2012.4401.4405
Abstract: Antioxidant activity of Aspirin Eugenol Ester (AEE) for aging model of mice by D-galactose for 8 weeks was investigated. MDA and lipofuscin contents of mice serum and heart, liver were selected as indexes to reflect antioxidant activity. The results showed that the small doses of AEE can effectively remove free radicals caused by D-galactose and large doses of AEE can make free radicals level below the normal level. There were some relationships between dose and effect. Compared with precursor drug aspirin and eugenol, AEE also has stronger antioxidant activity.
Increased p66Shc in the Inner Ear of D-Galactose-Induced Aging Mice with Accumulation of Mitochondrial DNA 3873-bp Deletion: p66Shc and mtDNA Damage in the Inner Ear during Aging  [PDF]
Lisa Wu, Yu Sun, Yu-Juan Hu, Yang Yang, Ling-Li Yao, Xing-Xing Zhou, Hao Wang, Rui Zhang, Xiang Huang, Wei-Jia Kong
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0050483
Abstract: Aging has been associated with mitochondrial DNA damage. P66Shc is an age-related adaptor protein that has a substantial impact on mitochondrial metabolism through regulation of the cellular response to oxidative stress. Our study aimed to establish a D-galactose (D-gal)-induced inner ear aging mouse model and to investigate the potential role of p66Shc and its serine 36-phosphorylated form in the inner ear during aging by using this model. Real-time PCR was performed to detect the mtDNA 3873-bp deletion and the level of p66Shc mRNA in the cochlear lateral wall. Western blot analysis was performed to analyze the total and mitochondrial protein levels of p66Shc and the level of Ser36-P-p66Shc in the cochlear lateral wall. Immunofluoresence was performed to detect the location of the Ser36-P-p66Shc expression in the cochlear lateral wall. The results showed that the accumulation of the mtDNA 3873-bp deletion, total and mitochondrial protein levels of p66Shc and level of Ser36-P-p66Shc were significantly increased in the cochlear lateral wall of the D-gal-treated group when compared to the control group and that Ser36-P-p66Shc was mainly localized in the cytoplasm of the cells in the stria vascularis. During aging, the oxidative stress-related increase of p66Shc and Ser36-P-p66Shc might be associated with the accumulation of the mtDNA 3873-bp deletion in the inner ear.
Antiaging Effect of Pine Pollen in Human Diploid Fibroblasts and in a Mouse Model Induced by D-Galactose
Gen-Xiang Mao,Ling-Di Zheng,Yong-Bao Cao,Zhuo-Mei Chen,Yuan-Dong Lv,Ya-Zhen Wang,Xi-Lian Hu,Guo-Fu Wang,Jing Yan
Oxidative Medicine and Cellular Longevity , 2012, DOI: 10.1155/2012/750963
Abstract: The present paper was designed to investigate the effect of pine pollen against aging in human diploid fibroblast 2BS cells and in an accelerated aging model, which was established by subcutaneous injections with D-galactose daily for 8 weeks in C57BL/6J mice. Pine pollen (1 mg/mL and 2 mg/mL) is proved to delay the replicative senescence of 2BS cells as evidenced by enhanced cell proliferation, decreased SA-β-Gal activity, and reversed expression of senescence-associated molecular markers, such as p53, p21Waf1, p16INK4a, PTEN, and p27Kip1 in late PD cells. Besides, pine pollen reversed D-galactose-induced aging effects in neural activity and inflammatory cytokine levels, as indicated by improved memory latency time and reduced error rate in step-down test and decreased concentrations of IL-6 and TNF-α in model mice. Similar to the role of AGEs (advanced glycation endproducts) formation inhibitor aminoguanidine (AG), pine pollen inhibited D-galactose-induced increment of AGEs levels thus reversed the aging phenotypes in model mice. Furthermore, the declined antioxidant activity was obviously reversed upon pine pollen treatment, which may account for its inhibitory effect on nonenzymatic glycation (NEG) in vivo. Our finding presents pine pollen as an attractive agent with potential to retard aging and attenuate age-related diseases in humans.
Effects of purslane herb on stress ability of aging mice induced by D-galactose  [cached]
Zhong Xi Yi Jie He Xue Bao , 2004,
Abstract: Objective: To investigate the effects of purslane herb aquenous extracts (PHAS) on the stress ability of aging mice induced by D-galactose.Methods: We odserved the survival time to hypoxia and heat survival rate of the mice treated with different doses of PHAS and vitamin E. The contents of lipofuscin and malondialdehyde (MDA), and the activity of superoxide dismutase (SOD) and catalase (CAT) in the brain and liver of the mice were tested. Results: As compared with vitamin E, three doses of PHAS (1.6, 0.8 and 0.4 ml/d) prolonged the survival time to hypoxia and the pole climbing time and increased the heat survival rate, and the 0.8 ml/d PHAS had the best effect.In the group of 0.8 ml/d PHAS, the activity of SOD and CAT decreased less, and the contents of lipofuscin and MDA decreased significantly.The effect of vitamin E was not as good as the PHAS. Conclusion: PHAS can prevent the stress ability of the aging mice.One of its mechanisms may be increasing the activity of SOD and CAT, hence decreasing the damage of the oxidation products to the body.
Ginkgo Biloba Extract EGB761 Protects against Aging-Associated Diastolic Dysfunction in Cardiomyocytes of D-Galactose-Induced Aging Rat
Jing Liu,Junhong Wang,Xiangjian Chen,Changqing Guo,Yan Guo,Hui Wang
Oxidative Medicine and Cellular Longevity , 2012, DOI: 10.1155/2012/418748
Abstract: The aim of the present study was to make use of the artificially induced aging model cardiomyocytes to further investigate potential anti-aging-associated cellular diastolic dysfunction effects of EGB761 and explore underlying molecular mechanisms. Cultured rat primary cardiomyocytes were treated with either D-galactose or D-galactose combined with EGB761 for 48 h. After treatment, the percentage of cells positive for SA-β-gal, AGEs production, cardiac sarcoplasmic reticulum calcium pump (SERCA) activity, the myocardial sarcoplasmic reticulum calcium uptake, and relative protein levels were measured. Our results demonstrated that in vitro stimulation with D-galactose induced AGEs production. The addition of EGB761 significantly decreased the number of cells positive for SA-β-gal. Furthermore, decreased diastolic [Ca2
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