Longevity Protein Protects Heart Muscle by Reducing Reactive Oxygen Species

The SIRT3 gene encodes a protein, (SIRT3), which exhibits NAD+-dependent deacetylase activity.

In the current study, investigators at the University of Chicago (IL, USA) worked with two different lines of genetically engineered mice. One line was engineered to lack the SIRT3 gene (SIRT3- defficient line), while the other Tg line was engineered to overexpress SIRT3.

Results published in the August 3, 2009, issue of the Journal of Clinical Investigation revealed that although SIRT3-deficient mice appeared to behave normally, they showed signs of cardiac hypertrophy and interstitial fibrosis at eight weeks of age. Stimulating these mice to develop hypertrophy produced a severe cardiac hypertrophic response, whereas the SIRT3-expressing Tg mice were protected from similar stimuli.

In primary cultures of cardiomyocytes, SIRT3 blocked cardiac hypertrophy by activating two forkhead box O3a–dependent (Foxo3a-dependent), antioxidant–encoding genes. The activation of manganese superoxide dismutase (MnSOD) and catalase (Cat) caused a decrease in cellular levels of reactive oxygen species (ROS). Excess ROS levels can harm a cell by damaging DNA or by oxidizing fatty acids or amino acids or by inactivating specific enzymes by oxidation of cofactors.

The authors concluded the paper with the statement, "These results demonstrate that SIRT3 is an endogenous negative regulator of cardiac hypertrophy, which protects hearts by suppressing cellular levels of ROS.”

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