SIRT3 deficiency decreases oxidative metabolism capacity but increases lifespan in male mice under caloric restriction

This project was the culmination of my work done at the University of Wisconsin with an immensely talented PhD student, Amy Qin. SIRT3, or sirtuin 3 is a mitochondrial deacetylase - meaning it is an enzyme that removes the acetyl chemical group from proteins, which are thought to make mitochondrial proteins function better. And indeed that was the case. Animals with SIRT3 performed better aerobically in all kinds of measures.

BUT, contrary to our hypothesis, removing SIRT3 (the knockout animals) resulted in animals living longer. So while their lifespan increased, their healthspan decreased.

Check it out in Aging Cell

Our working model:

Under caloric restriction, the SIRT3 knockout mice have to rely more on fatty acid oxidation as there seem to be some impairments in the mitochondria’s ability to use carbohydrates.