Sirtuin proteins have been shown to promote longevity in many organisms, and increased expression of one sirtuin protein, SIRT3, has been linked to increased human lifespan. New data, generated in mice, by Mahesh Gupta and colleagues, at the University of Chicago, Chicago, has revealed that Sirt3 helps protect the mouse heart.
In the study, the heart of mice lacking Sirt3 was found to show signs of becoming enlarged (a process known as cardiac hypertrophy), at about 8 weeks of age. Further, these mice responded dramatically to conditions that induce cardiac hypertrophy, whereas mice overexpressing Sirt3 were protected from cardiac hypertrophy under the same conditions.
Additional analysis revealed the mechanism by which Sirt3 blocks the cardiac hypertrophic response, thereby providing protection to the mouse heart. Specifically, it acts in heart muscle cells via the protein Foxo3a to increase expression of anti-oxidant proteins, thereby reducing levels of damaging oxidants.
Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice
- Sundaresan et al. Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. Journal of Clinical Investigation, 2009; DOI: 10.1172/JCI39162
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