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Resveratrol increases lifespan in bees

Resveratrol increases lifespan in bees
Photo courtesy of Brenda Rascon

Friday, September 28, 2012. The July, 2012 issue of the journal Aging reported the results of research involving honey bees which revealed an ability for resveratrol to reduce food intake and extend life.  Resveratrol is a compound found in red grapes and wine that has been found to provide some of the benefits of calorie restriction.  Although resveratrol has been shown to lengthen the lives of yeast, worms, fruit flies and mice, the study is the first to evaluate the effect of the compound in honey bees.

In the current study, a team that included David A. Sinclair at Harvard Medical School, as well as scientists at Arizona State University and the Norwegian University of Life Sciences compared the effects of an unenhanced honey bee diet to diets containing two different concentrations of resveratrol.  The lower concentration of resveratrol was associated with a 38 percent increase in average lifespan and the higher concentration with a 33 percent increase under normal oxygen conditions.  Maximum lifespan, which defines the longest lived members of a species (in contrast with average life expectancy) also increased in resveratrol-fed bees.  Exposure of the bees to a high oxygen environment designed to generate oxidative stress eliminated these effects.

"For the first time, we conducted several tests on the effects of resveratrol by using the honey bee as a model," announced lead author Brenda Rascón, who is an associate professor at Arizona State University's School of Life Sciences and the Norwegian University of Life Sciences. "We were able to confirm that under normal living conditions, resveratrol lengthened lifespan in honey bees."

In an effort to uncover the mechanisms involved in resveratrol's benefits, the researchers examined the compound's effect on appetite. In comparison with bees that did not receive resveratrol, those given the compound had less interest in consuming sugar solutions unless the sugar was highly concentrated. "Because what we eat is such an important contributor to our physical health, we looked at the bees' sensitivity to sugar and their willingness to consume it," Dr Rascón explained. "Bees typically gorge on sugar and while it's the best thing for them, we know that eating too much is not necessarily a good thing."

Further experimentation revealed that resveratrol reduced food consumption in bees allowed to eat as much as they liked of diets containing carbohydrate and protein. "Surprisingly, the bees that received the drug decreased their food intake," Dr Rascón reported. "The bees were allowed to eat as much as they pleased and were certainly not starving--they simply would not gorge on the food that we know they like. It's possible resveratrol may be working by some mechanism that is related to caloric restriction – a dietary regimen long known to extend lifespan in diverse organisms."

"In summary, we demonstrated that resveratrol significantly affected gustatory responsiveness and prolonged lifespan in wild-type honey bees under normal oxygen conditions," the authors concluded. "Our subsequent projects in honey bees will focus on using pharmacological agents to explore whether there is a SIRT1-dependence for the lifespan and neurophysiological effects noted here."

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Harvard Medical School professor of genetics David A. Sinclair and his associates confirm in the May, 2012 issue of the journal Cell Metabolism that the red wine compound resveratrol does indeed impact the longevity gene SIRT1, as well as affect other proteins. "This study provides the first in vivo evidence that beneficial effects of resveratrol on mitochondrial function require SIRT1," the authors announce.

Earlier research involving yeast, worms and flies had indicated that resveratrol targeted the sirtuin family of genes of which SIRT-1 is a member, but the findings, which were not duplicated in animals due to the fact that those in which the gene for SIRT1 is knocked out don't survive, had been called into question. The concern led one pharmaceutical company to suspend some of its research involving the compound. However, Dr Sinclair's team has now produced mice in which SIRT1 can be completely disabled during adulthood via administration of the drug tamoxifen and have shown that these animals don't experience improved mitochondrial function in response to resveratrol, while mice with normal SIRT1 exhibit increased mitochondrial formation and function. They determined that resveratrol targets SIRT1 at moderate doses and that other molecules, such as AMPK (which is also related to the mitochondria), are targeted at higher doses.

"Resveratrol improves the health of mice on a high-fat diet and increases life span," stated Dr Sinclair. "The results were surprisingly clear. Without the mitochondria-boosting gene SIRT1, resveratrol does not work."

"It's standard when you study molecules that you use the lowest dose that gives you an effect because of the risk of hitting other things if you use too much," he noted. "But for the downstream benefits on energy, you still need SIRT1. Our paper shows that SIRT1 is front and center for any dose of resveratrol."

 

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