Anti-aging Function Research Articles

Spermidine prevents high glucose-induced senescence in HT-22 cells by upregulation of CB1 receptor.

Hyperglycaemia-induced neurotoxicity involved in the pathogenesis of diabetic encephalopathy and neuronal senescence is one of the worst effects of hyperglyceamic neurotoxicity. Cannabinoid receptor type 1 (CB1) has neuroprotective function in a series of neuropathy. Spermidine (Spd) has anti-aging function in many tissues. However, the role of Spd in hyperglyceamia-induced neuronal senescence remains unexplored. Therefore, we used high glucose (HG)-treated HT-22 cell as vitro model to investigate whether Spd protects neurons against hyperglyceamia-induced senescence and the mediatory role of CB1 receptor. The HT-22 cells were cultured in HG condition in the presence ofdifferent dose of Spd. Then, the viability of cells was measuredby Cell Counting Kit-8 (CCK-8) assay. The senescence of cells was detected by Senescence-associated β-galactosidase (SA-β-Gal) staining. The expressions of p16INK4a , p21CIP1 and CB1 receptor were measured by western blot. We found that Spd inhibited HG-induced neurotoxicity (the loss of cell viability) and senescence (the increase of SA-β-Gal positive cells, the upregulation of p16INK4a and p21CIP1 ) in HT-22 cells. Also, Spd prevented HG-induced downregulation of CB1 receptor in HT-22 cells. Furthermore, we demonstrated that AM251 (a specific inhibitor of the CB1 receptor) reversed the protective effects of Spd on HG-induced neurotoxicity and senescence. These results indicated that Spd prevents HG-induced neurotoxicity and senescence via the upregulation of CB1 receptor. Our findings provide a promising future of Spd-based preventions and therapies for diabetic encephalopathy.

Antioxidant effect of peony seed oil on aging mice.

d-galactose was injected into mice of ages 4-5months, and peony seed oil was administered using an oral gavage to assess its possible anti-aging functions. The content of malondialdehyde (MDA) and the activities of monoamine oxidase (MAO), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) in the brain and liver of these mice were determined using biochemical kits. The significance of the differences in the content of the components associated with aging and anti-aging among each group was analyzed statistically. The MDA content and activities of MAO in the brain and liver of mice in the peony seed oil group were significantly lower than those in the aging group. The activities of GSH-Px, Cu/Zn-SOD, and Mn-SOD in the brain and liver of mice in the peony seed oil group were very significantly higher than those in the aging group. Peony seed oil was determined to have an obvious anti-aging function.

HIF-1-dependent regulation of lifespan in Caenorhabditis elegans by the acyl-CoA-binding protein MAA-1.

In yeast, the broadly conserved acyl-CoA–binding protein (ACBP) is a negative regulator of stress resistance and longevity. Here, we have turned to the nematode C. elegans as a model organism in which to determine whether ACBPs play similar roles in multicellular organisms. We systematically inactivated each of the seven C. elegans ACBP paralogs and found that one of them, maa-1 (which encodes membrane-associated ACBP 1), is indeed involved in the regulation of longevity. In fact, loss of maa-1 promotes lifespan extension and resistance to different types of stress. Through genetic and gene expression studies we have demonstrated that HIF-1, a master transcriptional regulator of adaptation to hypoxia, plays a central role in orchestrating the anti-aging response induced by MAA-1 deficiency. This response relies on the activation of molecular chaperones known to contribute to maintenance of the proteome. Our work extends to C. elegans the role of ACBP in aging, implicates HIF-1 in the increase of lifespan of maa-1 –deficient worms, and sheds light on the anti-aging function of HIF-1. Given that both ACBP and HIF-1 are highly conserved, our results suggest the possible involvement of these proteins in the age-associated decline in proteostasis in mammals.

The Anti-Aging Effect of Erythropoietin via the ERK/Nrf2-ARE Pathway in Aging Rats.

Erythropoietin (EPO) has a neuroprotective effect and can resist aging, which most likely occur through EPO increasing the activity of antioxidant enzymes and scavenging free radicals. In this study, we verified the anti-aging function of EPO and discussed the mechanism occurring through the extracellular signal-regulated kinase (ERK)/NF-E2-related factor 2 (Nrf2)-ARE pathway. A rat model of aging was induced by the continuous subcutaneous injection of 5% D-galactose for 6weeks. At the beginning of the sixth week, physiological saline or EPO was administered twice per day through a lateral ventricle system for a total of 7days. In one group, 2μl PD98059 was administered 30min before EPO. Learning and memory ability were analyzed with the Morris water maze system. HE staining was used to observe the morphological changes in the neurons in the hippocampus, and immunohistochemical staining as well as Western blots were carried out to detect the expression of ERK for each group of rats and the expression of phosphorylated-ERK (P-ERK), Nrf2, and superoxide dismutase (SOD). Real-Time PCR was carried out to detect the amount of Nrf2 mRNA and the KEAP1 mRNA expression. EPO can significantly improve learning and memory ability in aging rats and can provide protection against aging by improving the hippocampus morphology. Immunohistochemical staining and Western blots showed P-ERK, Nrf2, and Cu-Zn SOD decreases in aging rats compared to the normal group, while the expression for those proteins increased after EPO intervention. PD98059 inhibited the enhanced expression of P-ERK, Nrf2, and Cu-Zn SOD induced by EPO. Real-Time PCR results suggested that the trend of Nrf2mRNA expression was the same as that for the proteins, which confirmed that the enhancement occurred at the gene level. As such, EPO can significantly resist or delay aging and protect the brain by reducing oxidative stress. The most likely mechanism is that EPO can promote the ERK/Nrf2-ARE pathway in aging rats and that PD98059 can inhibit that process. These findings may facilitate further studies on the mechanism of aging and applications for the neuroprotective properties of EPO for clinical treatments.

Serum- and Glucocorticoid-Inducible Kinase 1 Delay the Onset of Endothelial Senescence by Directly Interacting with Human Telomerase Reverse Transcriptase.

Endothelial senescence is characteristic of vascular aging. Serum- and glucocorticoid-inducible kinase (SGK)1 belongs to a family of serine/threonine kinases regulated by various external stimuli. SGK1 has been shown to be protective against reactive oxygen species (ROS) production and to be involved in processes regulating aging. However, data on the direct relationship between SGK1 and senescence are sparse. In the present study, we sought to investigate the role of SGK1 in cellular aging by using human umbilical vein endothelial cells (HUVECs) infected with different constructs. Senescence was measured at different cellular stages by senescence-associated β-galactosidase (SA-β-gal) activity, human telomerase reverse transcriptase (hTERT) activity, p21 protein levels, and ROS production. HUVECs over-expressing full-length SGK1 (wild-type SGK1 [SGK1WT]) showed a decrease in SA-β-gal and p21 expression and a corresponding increase in hTERT activity in the early stages of aging. Moreover, SGK1WT presented lower levels of ROS production. A direct interaction between SGK1WT and hTERT was also shown by co-immunoprecipitation. The SGK1Δ60 isoform, lacking the amino-terminal 60 amino acids, did not show interaction with hTERT, suggesting a pivotal role of this protein site for the SGK1 anti-aging function. The results from this study may be of particular importance, because SGK1WT over-expression by activating telomerase and reducing ROS levels may delay the processes of endothelial senescence.

Recent advances in anti-aging study of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucopyranoside--a main component of Polygonum multiflorum

Aging is an inevitable process of life caused by a combination of organs and tissues events which manifests as loss of structure and function. It is accompanied with organ hypofunction, decline in defense against stress and energy metabolism, and lots of age-related diseases. Therefore, it is critical to understand the mechanism of aging, as well as to discover new drugs to slow aging. Polygonum multiflorum has long been recognized in traditional Chinese medicine as anti-aging medicine. Interestingly, its extract has been shown to prolong lifespan in drosophila and elegans. Tetrahydroxystilbene glucoside (TSG), the main ingredient of P. multiflorum, shares a strong structural similarity with resveratrol, a well-known anti-aging natural product. This review summarized up-to-date literature reports and our laboratory findings on the mechanism of TSG anti-aging efficiency and function against age-related disease. It could provide reference for searching for anti-aging tradition Chinese medicine.

Klotho-Dependent Cellular Transport Regulation.

Klotho is a transmembrane protein that in humans is encoded by the hKL gene. This protein is known to have aging suppressor effects and is predominantly expressed in the distal convoluted tubule of the kidney, parathyroid glands, and choroid plexus of the brain. The Klotho protein exists in both full-length membrane form and a soluble secreted form, which exerts numerous distinct functions. The extracellular domain of Klotho can be enzymatically cleaved off and released into the systemic circulation where it functions as β-glucuronidase and a hormone. Soluble Klotho is a multifunction protein present in the biological fluids including blood, urine, and cerebrospinal fluid of mammals. Klotho deficiency leads to multiple organ failure accompanied by early appearance of multiple age-related disorders and early death, whereas overexpression of Klotho results in the opposite effects. Klotho, an enzyme and hormone, has been reported to participate in the regulation of cellular transport processes across the plasma membrane either indirectly through inhibiting calcitriol (1,25(OH)2D3) formation or other mechanism, or by directly affecting transporter proteins, including ion channels, cellular carriers, and Na(+)/K(+)-ATPase. Accordingly, Klotho protein serves as a powerful regulator of cellular transport across the plasma membrane. Importantly, Klotho-dependent cellular transport regulation implies stimulatory or inhibitory effects. Klotho has been shown to play a key role in the regulation of multiple calcium and potassium ion channels, and various cellular carriers including the Na(+)-coupled cotransporters such as NaPi-IIa, NaPi-IIb, EAAT3, and EAAT4, CreaT1 as well as Na(+)/K(+)-ATPase. These regulations are parts of the antiaging function of Klotho, which will be discussing throughout this chapter. Clearly, further experimental efforts are required to investigate the effect of Klotho on other transport proteins and underlying molecular mechanisms by which Klotho exerts its effect.

Application of Titanium Dioxide Nanoparticles on Textile Modification

Titanium dioxide nanoparticles have the unique properties of optic character and can be used in textile region. In this paper, the application status, prepare methods of physical method and chemical method, application method of exhaustion, pad-dry-cure and coating methods in textile modification of titanium dioxide nanoparticles are introduced. The prepared mechanisms are then analysis. It is shown that titanium dioxide nanoparticles can provide ultraviolet-resistance fuction, anti-bacterial activity, infrared effects, anti-static eclectricity function, anti-aging function and Self-cleaning effect in textile modification. As last, the existed problems and tend to development are analysized.

Comparative Evaluation of Wrinkle Treatments

Skin wrinkles are one of the most cosmetically concerning signs of aging for women, and improvements in the visual effect of wrinkles become a matter of concern that has an impact on the quality of life. Although various wrinkle treatments are being tried in the area of aesthetics and noninvasive cosmetic surgery, no guideline on how to treat wrinkles exists to date. This study evaluated the clinical effects of four wrinkle treatment methods [fractional erbium yttrium-aluminum-garnet (YAG) laser treatment, intense pulsed light (IPL) therapy, CD-atRA external application, and nutritional therapy with intake of amino acid supplements]. These four methods were selected as promising candidates in a pilot case study to improve wrinkles by following the consensus guideline (Task Force Committee for Evaluation of Anti-Aging Function, J Jpn Cosmet Sci Soc 31:411-431, 2007) for the evaluation of anti-wrinkle effects issued by the Japan Cosmetic Industry Association. The wrinkle area fraction and skin viscoelasticity were measured by objective evaluation. Furthermore, a satisfaction survey of the subjects was conducted on the basis of subjective evaluations using the visual analog scale (VAS) method and in accordance with the guideline for the evaluation of antiwrinkle effects. Fractional erbium YAG laser treatment showed statistically significant improvement in both of the objective evaluations (wrinkle area and skin elasticity). The IPL method showed statistically significant improvement in both of the objective evaluations (wrinkle area and skin elasticity), and it especially demonstrated a more significant difference in skin elasticity. The CD-tretinoin external application method showed statistically significant improvement in both of the objective evaluations (wrinkle area and skin elasticity), and it especially demonstrated a more significant difference in wrinkle area. Nutritional therapy showed statistically significant improvement in wrinkle area, whereas IPL, CD-tretinoin external application, and nutritional therapy demonstrated statistically significant improvement in the degree of wrinkle. As for the subjective assessment of VAS, all four treatments demonstrated equivalent satisfaction. All four minimally invasive procedures (fractional erbium YAG treatment, IPL therapy, CD-atRA external application, and intake of amino acid supplements) showed significant improvement of wrinkles. Comparative evaluation of wrinkles using the same criteria is important. The findings clearly showed that an evidence-based approach to wrinkle treatments supported by validation of their effectiveness is required. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Alstonia scholarisR. Br. Significantly Inhibits Retinoid-Induced Skin IrritationIn VitroandIn Vivo

Topical retinoids inhibit matrix metalloproteinases and accelerate collagen synthesis, thereby triggering antiaging effects in the skin. However, topical retinoids can cause severe skin reactions, including scaling, erythema, papules, and inflammation. The present study demonstrates that the ethanolic bark extract of Alstonia scholaris R. Br. can significantly inhibit all-trans retinoic acid-induced inflammation in human HaCat keratinocyte cells. Furthermore, two representative retinoid-induced proinflammatory cytokines, monocyte chemoattractant protein-1 and interleukin-8, were significantly suppressed by A. scholaris extract (by 82.1% and 26.3% at 100 ppm, and dose-dependently across the tested concentrations) in vitro. In a cumulative irritation patch test, A. scholaris extract decreased retinol-induced skin irritation, while strengthening the ability of retinoids to inhibit matrix metalloproteinase-1 expression, which is strongly associated with aging effects. These results suggest that A. scholaris is a promising compound that may increase the antiaging function of retinoids while reducing their ability to cause skin irritation.

Morphological and biochemical signs of age-related neurodegenerative changes in klotho mutant mice

Klotho mutant mice, defective in the klotho gene, develop multiple age-related disorders with very short lifespans. Introduction of the exogenous klotho gene into these mutant mice leads to an improvement in their phenotypes, while overexpression of this gene in wild-type mice significantly extends their lifespan. These observations suggest that the klotho gene/protein has an anti-aging function. Since there have been only a few reports with some disagreement about results on the CNS of the mutant mice, we tried to clarify whether the CNS neurons generate aging-like features, even in premature stages, using biochemical and morphological approaches. Results obtained from the mutant mice, when compared with wild-type mice, were as follows. Neurofilaments (NFs) were increased significantly in axons, with the subunit proteins showing a significant enhancement in phosphorylation or expression of NF-H or NF-L, respectively. Microtubules in Purkinje cell dendrites were closer to each other, and in the CNS tissue tubulin was unaltered, but microtubule-associated protein (MAP) 2 was significantly reduced in expression. Neuronal cellular organelles were morphologically disordered. Lysosomes, cathepsin D and light chain 3 of MAP1A/B (LC3) were augmented with the appearance of putative autophagy-related structures. Antiapoptotic Bcl-xL and proapoptotic Bax were reduced and enhanced, respectively, and mitogen-activated protein kinase was reduced. Synapse-related proteins and structures were decreased. Neuronal degeneration was evident in hippocampal pyramidal cells, and possibly in Purkinje cells. Astrocytic glial filaments and glial fibrillary acidic protein were increased in density and expression, respectively. Together, the CNS neuronal alterations in klotho mutant mice were quite similar to those found in aged animals, including even premature death, so this mouse should be a more appropriate animal model for CNS aging than those previously reported.

Effect of the Chinese Traditional Medicine "Bushen Yinao Pian" on the Cerebral Gene Expression of the Senescence-Accelerated Mouse Prone 8/Ta

The effect of Chinese traditional medicine "Bushen Yinao Pian," a complex prescription used for anti-aging, on the cerebral gene expression of the senescence-accelerated mouse prone 8/Ta (SAMP8/Ta) had been studied with messenger ribonuclear acids reverse transcription differential display polymerase chain reaction (mRNA DDRT-PCR). Eight differential displayed bands had been discerned and sequenced. The sequences of those fragments are matched to adipocyte-specific protein-5; low density lipoprotein receptor-related protein associated protein-1; reticulon-3; cysteine and histidine-rich domain (CHORD)-containing, zinc-binding protein-1; cytochrome c oxidase subunit-2 (Cox-2); cytochrome c gene, MC1; DNA sequence from clone RP23-72M11 on chromosome X, respectively and a novel sequence fragment. Most of these genes are aging-related. It can be proved that the "Bushen Yinao Pian" truly has anti-aging function.

Coenzyme Q 10 can prolong C. elegans lifespan by lowering oxidative stress

The mev-1 gene encodes cytochrome b, a large subunit of the Complex II enzyme succinate-CoQ oxidoreductase. The mev-1( kn1) mutants are hypersensitive to oxidative stress and age precociously, probably because of elevated superoxide anion production in mitochondria. Coenzyme Q (CoQ) is essential for the mitochondrial respiratory chain. Here, we show that CoQ 10 and Vitamin E extended the life span of wild-type Caenorhabditis elegans. Conversely, only CoQ 10 recovered the life shortening effects seen in mev-1. We also show that CoQ 10 but not Vitamin E reduced superoxide anion levels in wild type and mev-1. Another previously described phenotype of mev-1 animals is the presence of supernumerary apoptotic cells. We now demonstrate that CoQ 10 (but not Vitamin E) suppressed these supernumerary apoptoses. Collectively these data suggest that exogenously supplied CoQ 10 can play a significant anti-aging function. It may do so either by acting as an antioxidant to dismutate the free radical superoxide anion or by reducing the uncoupling of reactions during election transport that could otherwise result in superoxide anion production. The latter activity has not been ascribed to CoQ 10; however, it is known that conditions that uncouple electron transport reactions can lead to elevated superoxide anion production.

Antioxidative and growth-promoting effect of selenium on senescing lettuce

In human and animal cells, Se plays an essential role in antioxidation and exerts an antiaging function but it is toxic at high dietary intake. To increase its intake in forage and foodstuffs, Se fertilization is adopted in some countries where soils are low in bioavailable Se, even though higher plants are regarded not to require Se. To test its ability to counteract senescence-related oxidative stress in higher plants, a pot experiment was carried out with lettuce (Lactuca sativa) cultivated with increasing amounts of H2SeO4. The yields harvested 7 or 14 weeks after sowing revealed that a low Se dosage (0.1 mg kg−1 soil) stimulated the growth of senescing seedlings (dry weight yield by 14%) despite a decreased chlorophyll concentration. The growth-promoting function was related to diminished lipid peroxidation. In young and senescing plants, the antioxidative effect of Se was associated with the increased activity of glutathione peroxidase (GSH-Px). In the senescing plants, the added Se strengthened the antioxidative capacity also by preventing the reduction of tocopherol concentration and by enhancing superoxide dismutase (SOD) activity. When no Se was added, tocopherols and SOD activity diminished during plant senescence. The higher Se dosage (1.0 mg kg−1 soil) was toxic and reduced the yield of young plants. In the senescing plants, it diminished the dry weight yield but not the fresh weight yield.