SIRT1, a protein that slows aging in mice and other animals, also protects against the ravages of a high-fat diet, including diabetes, according to a new MIT study.
MIT biology professor Leonard Guarente ’74 discovered SIRT1’s longevity-boosting properties more than a decade ago and has since explored its role in many different body tissues.
In his latest study, he looked at what happens when the SIRT1 protein is missing from adipose cells, which make up body fat.
When put on a high-fat diet, mice lacking the protein started to develop metabolic disorders, such as diabetes, much sooner than normal mice given a high-fat diet.
“We see them as being poised for metabolic dysfunction,” says Guarente, the Novartis Professor of Biology at MIT. “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.”
The finding raises the possibility that drugs that enhance SIRT1 activity may help protect against obesity-linked diseases.
Guarente first discovered the effects of SIRT1 and other sirtuin proteins while studying yeast in the 1990s. Since then, these proteins have been shown to coordinate a variety of hormonal networks, regulatory proteins and other genes, helping to keep cells alive and healthy.
In recent years, Guarente and his colleagues have deleted the gene from organs such as brain and liver to pinpoint its effects more precisely. Their previous work has revealed that in the brain, SIRT1 protects against the neurodegeneration seen in Alzheimer’s, Huntington’s and Parkinson’s diseases.
SIRT1 is a protein that removes acetyl groups from other proteins, modifying their activity. The possible targets of this deacetylation are numerous, which is likely what gives SIRT1 its broad range of protective powers, Guarente says.
In the Cell Metabolism study, the researchers analyzed the hundreds of genes that were turned on in mice lacking SIRT1 but fed a normal diet, and found that they were almost identical to those turned on in normal mice fed a high-fat diet.