Anti-aging Activities of Resveratrol in Rats
|School||Ocean University of China|
|Keywords||Resveratrol Immune response Senescence Glutamate cysteineligase|
Aging affects the immune system, leading to diminished overall functions. Thisphenomenon has been termed immunosenescence, which is clearly manifested byage-dependent defects in both humoral and cell-mediated immune responses.Resveratrol (3,5,40-trihydroxystilbene; RSV), a polyphenol, is a bioactive substancewith multiple functions, and occurs naturally in several plant species includinggrapevines and berries. Accumulating data have suggested that RSV hasanti-carcinogenic, anti-inflammatory, anti-microbial, anti-viral and anti-oxidantproperties that might be relevant to chronic diseases and/or longevity in humans.However, the mechanism underlying these observed anti-aging andimmunoregulation effects is poorly understood. The present study was undertaken toaddress the effect of dietary intake of resveratrol on the adaptive immunity andexpression of the glutamate cysteine ligase in aged rats.The hematologic indexes of the blood and the biochemical parameters of theserum were analyzed using flow cytometry and enzymatic analysis. Body weightswere not significantly affected by dietary RSV supplementation.The results revealedthat haemotological indice and biochemical parameters including ALT/AST activitiesand TG, TC, HDL and LDL levels of young, middle-aged and aged rats all remainedsimilar among the diet groups, suggesting that general physiology of rats was notaffected by dietary RSV supplementation.Among in vivo parameters of T cell-mediated immune response, thedelayed-type hypersensitivity (DTH) reaction is depressed with aging. Particularly,low or no DTH responses are often predictive of morbidity and mortality. The Tcell-dependent humoral response (antigen-specific antibody production) wasmeasured after immunization of rats with KLH. The response was calculated as thedifference in ear thickness of the rats before and after challenge with a recall antigen.Dietary RSV supplementation significantly affected the DTH response in aged rats.Although the B cell compartment of the immune system is only influenced to a minor extent by immuno-senescence, antigen-specific responses to vaccination arealtered with aging. The levels of KLH-specific IgG, IgG1and IgG2in the bloodwere measured by an enzyme-linked immunosorbent assay (ELISA). Levels ofanti-KLH IgG, anti-KLH IgG1and anti-KLH IgG2were both significantlyincreased in aged rats fed RSV-supplemented diet.One of the best characterized changes commonly observed in elderly subjectsand old mice is the deficiencies in T cell functions that are exemplified by decreasedT cell memory and exhaustion of the na ve T cell population with involution of thethymus. The percentages of major T and B cell subsets in spleen were assayed usingfluorescence-activated cell sorting (FACS) analysis. Proliferation of splenocytes werestimulated by ConA, LPS and KLH. RSV supplementation caused a significantincrease in the percentage of T helper cells (CD4+) in spleen from aged rats.GSH plays multiple physiological functions, including maintenance of cellularreduction-oxidation (redox) state, lipid peroxides and non-enzymatic scavenging offree radicals. GSH is synthesized de novo in a two-step process catalyzed by glutamate cysteineligase (GCL, EC184.108.40.206), formerly known as gamma-glutamylcysteine synthase (GCS), and GSHsynthase (GS, EC220.127.116.11). GCL catalyzes the first and rate-limiting step, in which glutamate isligated with cysteine to form-glutaamylcystein (-GC), which is rapidly linked to glycine to formGSH via action of GS. Semi-quantative real time-PCR (qRT-PCR) was used to assay themRNA expression of GCLc and GCLm subunit. GCL activity was determined by afluorescence assay. Protein contents were determined by Western blotting. Theseresults indicated that the decrease in GCL activity in aged rats could be reversed byRSV. Oral administration of RSV induced a remarkable increase in mRNA levels andprotein contents in livers, hearts and brains.In summary, this study highlights the anti-aging and immunostimulatoryproperties of RSV via enhancing in vivo humoral and cell-mediated immuneresponses in aged rats. It also suggests that the anti-oxidant properties of RSV viaenhancing GCL activity in vivo in aged rats. It also boosts the notion that late onset nutritional interventions with RSV may help aged organisms to generate an anti-agingeffect and improved redox state.