SIRT5 Regulates Mitochondrial Metabolism in Aging and Disease

2013 new Scholar Award in aging

In the next 50 years, the world's population aged 60 and over will more than triple from 600 million to 2 billion and carries the risk of significant social and economic burden if healthy aging cannot be maintained. Current research on aging has largely focused the molecular mechanisms of age-related diseases, and mitochondrial dysfunction has been associated with several human diseases of aging. However, the mechanisms are not known. Chemical modifications to mitochondrial proteins control several aspects of mitochondrial function. The long-term goal of this project is to understand how these modifications are regulated by the NAD+-dependent sirtuin deacylases and their influence on the diseases of aging. Little is known about the mitochondrial sirtuin 5 (SIRT5). We have recently discovered a novel enzymatic activity for SIRT5 called glutarylation. Coupled with its known desuccinylase activity, these findings position SIRT5 to be a crucial regulator of mitochondrial function and the aging process.

Matthew Hirschey Ph.D.
Duke University