Life Extension Update
Resveratrol protects overweight mice
An article published online on November 1, 2006 in the journal Nature reported the results of a study conducted by Rafael de Cabo, PhD, at the National Institute on Aging, David A. Sinclair, PhD, at Harvard Medical School, and an international group of researchers who found that resveratrol improved the health and survival of overweight older mice on high calorie diets.
Middle aged (one year old) mice were divided to receive a diet high in calories and fat, the same diet supplemented with resveratrol, or a standard diet. After six months, mice given resveratrol experienced greater insulin sensitivity and increased survival compared to mice on the high calorie diets that did not receive the compound. Livers of the mice that received resveratrol were half the size of those in mice on unsupplemented high calorie diets. Gene expression analysis of the liver found that resveratrol affected some of the metabolic pathways that are also influenced by calorie restriction. "We made a striking observation," stated Dr Sinclair, who is an associate professor of pathology at Harvard Medical School and codirector of the Paul F. Glenn Labs for the Biological Mechanisms of Aging. “Resveratrol opposed the effects of high caloric intake in 144 out of 153 significantly altered pathways. In terms of gene expression and pathway comparison, the resveratrol fed group was more similar to the standard diet fed group than the high calorie group.”
At 114 weeks of age, untreated overweight mice had higher plasma levels of insulin, glucose, and insulin-like growth factor compared to overweight mice who received resveratrol. Forty-two percent of the mice who received resveratrol or were on the standard diet had died at this point, compared to 58 percent of the mice on the high calorie diet who did not receive the compound. “The median lifespan increase we are seeing is about 15 percent at this point,” stated Dr Sinclair. "We won't have final lifespan numbers until all of the mice pass away, and this particular strain of mouse generally lives for two-and-a-half-years. So we are around five months from having final numbers, but there is no question that we are seeing increased longevity.
"They are also living more active, better lives,” he added. “Their motor skills actually show improvement as they grow older."
The team additionally found evidence of the activation of SIRT1, the mammalian version of the sirtuin enzyme Sir2, which is activated in yeast and other lower organisms by resveratrol.
"Mice are much closer evolutionarily to humans than any previous model organism treated by this molecule, which offers hope that similar impacts might be seen in humans without negative side effects," Dr Sinclair observed. "The 'healthspan' benefits we saw in the obese mice treated with resveratrol, such as increased insulin sensitivity, decreased glucose levels, healthier heart and liver tissues, are positive clinical indicators and may mean we can stave off in humans age-related diseases such as type 2 diabetes, heart disease, and cancer, but only time and more research will tell."
Despite its promise to extend life, caloric restriction remains a misunderstood lifestyle. People imagine that caloric restriction is associated with near-starvation and constant hunger, or malnutrition due to inadequate intake of dietary nutrients. In fact, caloric restriction, if undertaken correctly, is a healthy lifestyle that is accompanied by weight loss, only occasional hunger, optimal nutrition, and other health benefits. To stress the importance of a healthy lifestyle, caloric restriction will henceforth be referred to as "caloric restriction with optimal nutrition" or CRON.
The relationship between insulin and diabetes (and heart disease) is well established. Insulin is a critical hormone that enables the transport of blood sugar (glucose) into our cells, where it is used to generate energy. As people age, their cells become resistant to insulin, a condition called insulin resistance. In response, blood levels of insulin rise, along with blood levels of glucose. This condition of elevated glucose and insulin is a major risk factor for type 2 diabetes. CRON not only prevents these changes but can substantially reverse them. In fact, some researchers believe that CRON’s ability to extend life span is related to its ability to modulate insulin and glucose levels.
Increased life span in yeast can be induced by adding resveratrol, an antioxidant found in red wine, to their growth medium. These results have been replicated in both worms (Caenorhabditis elegans) and pomace flies (Drosophila melanogaster) (Wood JG et al 2004), suggesting that the action of resveratrol may be equivalent to that of caloric restriction. Whether resveratrol will prove to be a caloric restriction agent in mammals, primates, and humans remains to be seen.
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