Longevity Protein Has Diabetes-Prevention Qualities

Date: Aug-10-2012According to a study published in the journal Cell Metabolism, researchers at MIT have discovered that a protein, which has been shown to slow aging in animals, also protects against the detrimental effects of a high-fat diet, including diabetes.

More than ten years ago, Leonard Guarente, a biology professor at MIT, discovered that the protein SIRT1 had properties that boosted longevity. Since then Guarente has investigated how the protein works in several different body tissues.

In this study, Professor Guarente set out to determine what happens when the protein is missing from adipose cells, which made up body fat.

Guarente fed mice a high-fat diet and discovered that mice lacking SIRT1 started to develop metabolic disorders, such as diabetes, significantly faster than normal mice consuming a high-fat diet.

Guarente, the Novartis Professor of Biology at MIT, explained:

"We see them as being poised for metabolic dysfunction. You've removed one of the safeguards against metabolic decline, so if you now give them the trigger of a high-fat diet, they're much more sensitive than the normal mouse."

Results from the study indicate that medications designed to enhance SIRT1 activity may help protect against diseases associated to obesity.

The effects of SIRT1 and other sirtuin proteins were discovered by Guarente while he was studying yeast in the 1990s. According to the researchers, these proteins have been shown to help keep cells alive and healthy, coordinate a variety of hormonal networks, regulatory proteins and other genes.

In order to examine the effects of the gene more precisely, the researchers deleted the gene from organs such as the brain and liver. In earlier studies, the team found that SIRT1 protects against neurodegeneration in the brain observed in diseases, such as Alzheimer's, Parkinson's and Huntington's diseases.

SIRT1 removes acetyl groups from other proteins by modifying their activity. According to Guarente "the possible targets of this deacetylation are numerous, which is likely what gives SIRT1 its broad range of protective powers."

In the latest study, the team examined hundreds of genes that were switched on in the mice lacking SIRT1 and discovered they they were almost the same as those switched on in normal mice fed a high-fat diet.

According to the researchers, this finding indicated that in normal mice, development of metabolic disorders is a two-step process. Guarente explained: "The first step is inactivation of SIRT! By the high-fat diet, and the second step is all the bad things that follow that."

The team set out to determine how this happens and discovered that in normal mice consuming a high-fat diet, the protein is attached by an enzyme called caspase-1, which is induced by inflammation.

Guarente said:

"It's already known that high-fat diets can provoke inflammation, though it's unclear exactly how that happens. What our study says is that once you induce the inflammatory response, the consequence in the fat cells is that SIRT1 will be cleaved."

Anthony Suave, an associate professor of pharmacology at Weill Cornell Medical College, who was not part of the study, said that the study finding "provides a nice molecular mechanism to understand how inflammatory signals in adipose tissue could lead to rapid derangement of metabolic tissue.

Drugs that target that inflammatory process, as well as drugs that enhance sirtuin activity, might have some beneficial therapeutic effect against obesity-related disorders."

In addition, the team discovered that as normal mice grew older, they were more vulnerable to the impacts of a high-fat diet than younger mice. According to the researchers, this finding indicates that as mice age, they lose the protective effects of SIRT1.

Aging is also known in increase inflammation, and as a result Guarente is currently investigating whether age-related inflammation also provokes SIRT1 loss.

The study was supported by the National Institutes of Health, the Glenn Medical Foundation and the American Heart Association.

Written by Grace Rattue

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