| Due to the China’s family planning policy and increased quality of the medicalcare system, the quantity of elder people has risen gradually during recent years inChina. Much of population in China now survives to the point that chronic diseasesare major determinants of morbidity and mortality, although China now is only adeveloping country. How to find a way to delay onset of aging-related diseasesbecame an important social problem. However, the current vertebrate models using inaging research normally have a relative long lifespan. Researchers need to find a newmodel with a short lifespan. Nothobranchius has a media lifespan for N. furzeri GRZstrain of only 9 weeks，accelerated expression of age markers and capability of beingkept in a laboratory environment. In several studies of Nothobranchius, it found thatthe mortality rate rose gradually and cognitive ability deceased during aging, theexpression of senescence-associated (SA)-β-galactosidase, accumulation of lipofuscinincreased and the telomere length shorted with age. However, in N. guentheri, thechanges of those aging-related markers have not been reported so far.Resveratrol is a plant-derived natural chemical found in the skins of grapes, redwine, peanuts and rhubarb.In invertebrates, it is initially reported that resveratrol prolongs the lifespan inyeast, worms and flies. Resveratrol mimics the ability of caloric restriction in severalstudies because the prolongevity effect of resveratrol is only observed under full dietsbut not restricted diets. The lifespan extension is dependent on functional Sir2, whichis the member of sirtuin family and acts as a nicotinamide adenine dinucleotide(NAD)-dependent deacetylases. In vertebrate model of Nothobranchius, resveratrol prolongs the longevity of the GRZ strain of N. furzeri up to 56%. Further, it retardscognitive aging and neurodegeneration. Different from the observations in the modelsabove, resveratrol increases survival in mice fed a high fat diet such that their lifespanis equivalent to mice fed a normal diet, but failed to increase the lifespan of normallean mice. Other studies indicate that resveratrol acts as an anti-oxidative chemicalwhich attenuates oxidative damage. Moreover, several recent studies fail to observethe lifespan extension induced by resveratrol in yeast, worms and flies. Furthermore,several evidences demonstrate that the effect of resveratrol on the sirtuin issubstrate-specific in vitro. Bass et al. also found that the effect of resveratrol on thelifespan of C. elegans does not depend on sirtuin. Further understanding of howresveratrol affects the lifespan and body health in different animals will open up amagnificent prospect of pharmacological investigation.The fish was randomly divided into two groups, namely the resveratrol-treatedgroup (RES) and the control group (CTR). The former was started resveratrolsupplementation feeding with the dosage of 200μg/g after the separation; the latterremain fed with normal food. In our research, we tested the effects of resveratrol onlongevity, behavior and aging-related histology markers in N. guentheri.For longevity, our results showed that resveratrol prolonged the mean lifespan ofN. guentheri by 19% from 43 to 51 weeks and maximum lifespan by 28% from 64 to82 weeks. The prolongecity effects of resveratrol were observed both in males andfemales. However, resveratrol did not affect their body weight and the body lengthcompared to the control fish at 10 months of age.To further reveal the role of resveratrol in N. guentheri, we chose threeindependent experiments (conditioned place preference, active avoidance test andopen-field-like assay) to exhibit the effects of resveratrol supplementation on behavior.For conditioned place preference, compared to control group, fish inresveratrol-treated group showed a early increase in the percentage of time spent inthe context conditioned part (i.e., red zone prior to food administration) of the tankafter conditioned stimulate (CS, i.e. red color) was presented during the Conditioningphase. Then fish were tested in a T-maze following the Conditioning phase in order to determine whether N. guentheri can generalize a CS to a new environment. Both theresveratrol-treated and control fish demonstrated a preference of the red arm of themaze. But the statistical significant increase was only observed in resveratrol-treatedgroup. In active avoidance test, resveratrol-treated fish got the ability to pass thehurdle efficiently and had 59% rate of successes while the success rate only reached43% in control fish. Supplementation of resveratrol resulted in a significant increaseof cognitive ability. We also used an open-field-like assay to quantify the locomotorand exploratory activity by automated video tracking system. Our results showed thatfish in resveratrol-treated group have increased swimming performance. Those resultsimplied that resveratrol improved cognitive ability in N. guentheri.For aging-related histology markers, we detected the neurodegeneration,accumulation of lipofuscin and activity of SA-β-galactosidase in N. guentheri. Weused Fluoro-Jade B to analyse the effects of resveratrol on neurodegeneration. Theresults showed that resveratrol reduced the level of neurodegeneration. In the brainsections at the optic tectum, the degenerative striatal neurofibrils were labeled byFluoro-Jade B and numerously observed in the control fish but rarely detected in theresveratrol-treated animals. For lipofuscin, lipofuscin granules were observed in thecytoplasm of the hepatocytes in a packed pattern under fluorescent microscope. Theautofluorescence of lipofuscin in the resveratrol-treated group were fewer and darkerthan in the control group. We next detected the expression of SA-β-galactosidaseactivity in the skin of N. guentheri. We surveyed the labelling of coronal sections ofthe caudal peduncle. Activity of SA-β-galactosidase (pH 6.0) was shown by stainingthe sections with X-gal. The positive stained areas were larger in the control groupthan in the resveratrol-treated group. Those results indicated that resveratrol may haveglobal effect on aging in N. guentheri. |
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