SIRT3 regulates progression and development of diseases of aging

• Acetylation influences almost every major mitochondrial pathway.
• Mice lacking SIRT3 develop several diseases of aging at an accelerated rate.
• SIRT3KO mice might be considered a model of accelerated aging.

The mitochondrial sirtuin SIRT3 is a protein deacylase that influences almost every major aspect of mitochondrial biology, including nutrient oxidation, ATP generation, reactive oxygen species (ROS) detoxification, mitochondrial dynamics, and the mitochondrial unfolded protein response (UPR). Interestingly, mice lacking SIRT3 (SIRT3KO), either spontaneously or when crossed with mouse models of disease, develop several diseases of aging at an accelerated pace, such as cancer, metabolic syndrome, cardiovascular disease, and neurodegenerative diseases, and, thus, might be a valuable model of accelerated aging. In this review, we discuss functions of SIRT3 in pathways involved in diseases of aging and how the lack of SIRT3 might accelerate the aging process. We also suggest that further studies on SIRT3 will help uncover important new pathways driving the aging process.