Anti-aging Activity of Selected Nutraceuticals in Drosophila melanogaster.

摘要

Aging is a complex biological process involving both genetic and environmental factors. Age-related accumulation of oxidative damage is one of the most widely accepted and well studied mechanisms to underlie aging. Therefore, augmentation of antioxidant defenses shall be conducive to lifespan extension. Dietary manipulations, including calorie restriction and dietary supplementation, have been demonstrated to be able to extend lifespan and ameliorate certain age-related diseases. Nutraceuticals rich in antioxidants have the potentials to be competent anti-aging candidate compounds. The present study was to investigate the anti-aging activity of four nutraceuticals, including black tea extracts (BTE), soybean isoflavones (SIF), apple polyphenols (AP), and blueberry extracts (BBE), in Drosophila melanogaster, an aging model.;Consumption of tea, soybean, apple, and blueberry has been associated inversely with cardiovascular diseases, various cancers, and hypercholesterolemia. However, few existing reports have investigated their lifespan prolonging activity or their abilities to ameliorate neurodegenerative diseases in vivo. The present research studied the effect of the above four functional foods or nutraceuticals on the lifespan of fruit fly under both the normal physiological and the oxidative stress conditions.;For the first part, life spans of fruit flies, fed on either control diet or diet with varying doses of supplements, were recorded. At the same time, endogenous antioxidant enzyme activities, lipid peroxidation (LPO) level, expression of genes related to antioxidant system, longevity determination, and age-related diseases were investigated at selected time points throughout the entire life of flies; As for the second part, similar experiment protocols were conducted, detecting various survival parameters and changes at molecular level, for fruit flies living under certain oxidative stress, such as, 10% lard fatty acid in diet, intensive paraquat (PQ)/hydrogen peroxide (H 2O2) challenge, or chronic PQ exposure.;Results showed that 10 mg/ml of BTE, SIF, AP or 5 mg/ml of BBE in diet had the anti-aging activity in fruit flies. The mean life spans were increased by at least 10%. On the one hand, those foods or nutraceuticals could in general elevate expressions and activities of endogenous antioxidant enzymes as well as lower LPO level to certain degrees in fruit flies. On the other hand, longevity determined gene MTH was down-regulated by AP or BBE in diet.;The present study also investigated the potentials of selected nutraceuticals in antagonizing exogenous oxidative challenge and alleviating neurodegenerative diseases. Addition of 10% fatty acid derived from lard significantly shortened the maximum lifespan from 74 to 15 days in fruit flies. Administration of 10 mg/ml BTE in diet could prolong it to 28 days, increasing by 87%. Gene expression of CAT was down-regulated significantly with addition of lard fatty acids into diet while BTE supplementation could partially restore it to normal level. A similar changing pattern was observed in CAT activity test. However, SIF did not show a comparable activity in this assay.;In addition, pretreatment of BTE, AP, or BBE could enhance the resistance to intensive oxidative stress induced by PQ / H2O2 in OR flies but not in SODn108 or CAT n1 mutant flies. Chronic exposure to PQ could shorten lifespan of fruit flies from more than 73 to less than 35 days while it reduced their climbing ability by more than 60%. At the same time, PQ exposure led to a reduced expression of SOD, CAT, and Rpn11 with accumulation of ubiquitinated proteins. Consumption of AP or BBE could partially and significantly slow or reverse the aging process and locomotive dysfunction as well as elevate expressions and activities of the antioxidant enzymes and Rpn11 in fruit flies.;Furthermore, to exclude the possibility that the anti-aging activity of selected nutraceuticals in fruit flies was actually due to food restriction. Body weight tracking and food intake comparison were conducted in the present study. Results revealed no difference in average body mass and stomach redness index between the flies in control and experimental groups, proving that the anti-aging activity of these foods and nutraceuticals was not mediated by caloric restriction.;In conclusion, the present study demonstrated that BTE, SIF, AP, or BBE in diet could prolong the mean lifespan of fruit flies. Therein, BTE could reduce the high mortality rate caused by a high-fat diet; AP or BBE was able to alleviate PQ-induced mortality rate and restore the decline of locomotive activity in fruit flies. The anti-aging and anti-neurodegenerative activities were at least partially mediated by their interaction with endogenous antioxidant system, Rpn11, and MTH. Furthermore, it has also been proved that this lifespan-prolonging activity was not due to changes in food intake.