Calorie Restriction (CR) diets that reduce calories about 35% below normal have been shown to increase average life expectancy across a large assortment of animal species (though the longevity enhancing effect of CR has not yet been confirmed in humans). The life extending effect of CR has been the subject of a great deal of research attention as researchers have sought to find compounds that will throw the body into a metabolic state that is like the CR state. The hope is that a drug could provide the same life extending effects but without the need to feel perpetually hungry and to look gaunt.
Some researchers have been comparing the pattern of gene expression found in mice on CR diets with the patterns of gene expression found in mice given a variety of drugs. Some already used drugs may induce a metabolic state that will extend life expectancy by the same mechanism that CR diets extend life expectancy.
Investigators from an international consortium of research institutes, including the Johns Hopkins Bloomberg School of Public Health, have identified compounds that mimic the effects of a low-calorie diet without changing the amount of essential nutrients.
The lack of PPARalpha prevented some of the changes in metabolism normally seen on a CR diet.
Lead author, J. Christopher Corton, PhD, with ToxicoGenomics in Chapel Hill, NC, examined the genetic changes that occur during calorie restriction in mice that were fed a diet for one month containing about 35 percent fewer calories than a normal diet. He explained that these genetic changes, which are referred to as a transcript profile, can be used like a bar-code to distinguish a unique profile from other genetic changes that occur in the body. The researchers compared the profile of calorie restriction with the profiles produced by compounds known to have some properties similar to calorie restriction, including the ability to suppress factors that lead to a number of diseases.
The compounds that shared the greatest similarities in the bar codes included those that have activity toward receptors of interest to the pharmaceutical industry. The receptors include those that are targeted by drugs used to treat high cholesterol and triglyceride levels. One of the receptors, called PPARalpha, is a target for drugs that are currently used to treat high cholesterol and triglyceride levels in people at risk for heart disease.
The investigators also compared responses in normal mice to mice that lack a functional PPARalpha to determine if PPARalpha was directly involved in any of the responses that are induced by calorie restriction. They found that the PPARalpha-mutant mice lack many of the characteristics of calorie restriction, including changes in genes that may play important roles in heart disease and cancer. Calorie restriction is also known to protect animals from chemical exposure, and the investigators found that the protection afforded by calorie
It may turn out to be the case that some existing drugs that target PPARalpha are already benefitting their users by inducing a metabolic state that is similar to the state induced by calorie restriction.
The press release above does not indicate which cholesterol lowering drugs the researchers were using. However, my suspicion is that they were using statin drugs since statin drugs are known to activate PPARalpha. Well, Lipitor and Crestor users might be benefitting from CR-like effects on their bodies.
|Share |||Randall Parker, 2004 August 13 04:14 AM Aging Studies|