A new MIT study has found that a protein that slows aging in mice and other animals also helps fight against the damages of a high-fat diet, including diabetes.

Over a decade ago, SIRT1’s longevity-boosting properties were discovered by MIT biology professor Leonard Guarente, who has continued to examine its role in various body tissues. His recent study, appearing August 8th in the journal Cell Metabolism, observed what happens when the SIRT1 protein is missing from adipose cells, which make up body fat.

The research team put mice on a high-fat diet and realized that they started to develop metabolic disorders, like diabetes, when they lacked the protein, while normal mice given the same diet did not develop these disorders as quickly.

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.”

This finding suggests that drugs that enhance SIRT1 activity could possibly help fight against obesity-linked diseases.

While the expert studied yeast in the 1990s, he first discovered the effects of SIRT1 and other sirtuin proteins. These proteins have since shown to help keep cells alive and healthy by coordinating a variety of hormonal networks, regulatory proteins, and other genes.

In order to pinpoint the gene’s effects more accurately, Guarente and his team deleted the gene from organs such as the brain and the liver. Their past research has shown that in the brain, SIRT1 protects against the neurodegeneration seen in Huntington’s, Alzherimer’s, and Parkinson’s diseases.

SIRT1 is a protein that is known for removing acetyl groups from other proteins while modifying their activity. According to Guarente, the possible targets of this deacetylation are numerous, allowing SIRT1 to have its broad range of protective powers.

The hundreds of genes that were turned on in mice that were fed a normal diet lacking SIRT1 were analyzed by the team. They found that they were almost identical to those genes turned on in normal mice that were given a high-fat diet.

These results suggest that the development of metabolic disorders is a two-step process in normal mice. He said, “This first step is inactivation of SIRT1 by the high-fat diet, and the second step is all the bad things that follow that.”

The scientists wanted to investigate how this occurs and discovered that in normal mice fed a high-fat diet, the SIRT1 protein is cleaved by an enzyme (caspase-1), which is induced by inflammation. They were already aware that inflammation can develop from high-fat diets, though it is still unknown how that exactly happens.

Guarente said:

“What our study says is that once you induce the inflammatory response, the consequence in the fat cells is that SIRT1 will be cleaved.”

As normal mice grew older, the researchers discovered that they became more susceptible to the effects of a high-fat diet than younger mice, showing that the protective effects of SIRT disappear as they age. Knowing that inflammation increases with age, Guarente is now researching if age-related inflammation also provokes SIRT1 loss.

Written by Sarah Glynn