Cutting Calories May Stress Cells, Prompting Genes to Spur Cell Survival in Lab Tests
Scientists may have a new clue about how calorie restriction may lengthen life.
Previous research has linked calorie restriction to longevity, though many of those studies have been done in rodents and other short-lived species including worms, flies, and yeast.
Certain genes may be the link between calorie restriction and cell survival, a new study shows. Those genes, called SIRT3 and SIRT4, might eventually be targets for drugs to treat age-related diseases, according to Harvard Medical School's David Sinclair, PhD.
Sinclair's team studied a complex chemical chain reaction in which these genes nudge cells to live longer in the face of stress.
That stress came in the form of a two-day fast for rats studied by Sinclair and colleagues.
After the rats finished fasting, the researchers studied the rats' livers. They noticed that a protein called NAD+ was present at higher-than-normal levels in the rats' cellular powerhouses (mitochondria).
In earlier lab tests, the scientists had already linked increased NAD+ levels to the SIRT3 and SIRT4 genes.
Basically, those genes boost production of another chemical, which in turn boosts NAD+ levels -- and the whole process hinges on the cells being stressed (in this case, by the rats' fasting).
The study, published in the journal Cell, doesn't prove that a two-day fast -- or lengthier calorie restriction -- will extend human life span. But the findings may help explain the inner workings of cells during calorie restriction.
"Theoretically, we can envision a small molecule that can increase levels of NAD, or SIRT3 and SIRT4 directly, in the mitochondria," Sinclair states in a Harvard Medical School news release. "Such a molecule could be used for many age-related diseases."
Sinclair is a co-founder of Sirtris Pharmaceuticals, which is developing drugs that target SIRT genes.
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