SIRT3 Protein Needed for Supplement to Aid Heart in Friedreich’s Ataxia, Study Suggests
A protein called SIRT3 was essential to restore the heart contractility and energy metabolism that can result from an energy-promoting supplement called nicotinamide mononucleotide (NMN), researchers report from a study in Friedreich’s ataxia mouse models.
Previous studies have shown that the supplement increased levels of NAD+, a molecule that helps mitochondria — the cell’s powerhouse — generate energy from food. The additional energy helped improves heart function in several diseases.
But scientists didn’t know the exact mechanism that led from NAD+ activation to improved heart function.
Using mice with Friedreich’s ataxia, researchers investigated the effect that the mitochondrial protein SIRT3 had on heart function.
A key question that scientists had not answered was whether increasing levels of SIRT3 would have a therapeutic effect, the researchers wrote. “We set out to determine the efficacy of NMN [nicotinamide mononucleotide] supplementation in the [mice with Friedreich’s ataxia] and to test the role of SIRT3 in mediating the effects of NMN.”
When the study started, heart cells of the diseased mice had low levels of Sirt3 mRNA, a gene transcript that generates the protein. When the mice received the supplement, their heart function was restored.
Researchers then created a mouse model of the disease that lacked SIRT3. They wanted to know if the improvement seen depended on the activity of this specific protein. They discovered that supplementation had no effect on the mice, proof that SIRT3 is essential to NMN’s effect.
Together, the results provided valuable information on the supplement’s ability to improve heart function in Friedreich’s ataxia patients and the essential role of SIRT3 in this effort.
“Here, we report SIRT3-dependent restoration of cardiac function and energy metabolism upon NMN supplementation in the [mouse model’s] failing heart,” the researchers wrote.
Friedreich’s ataxia is an incurable neurodegenerative disease in children. It stems from a mutation that leads to less than normal production of the frataxin protein.
The low levels of frataxin lead to muscle weakness, abnormal sensitivity in limbs, movement problems, alterations in the structure of the cerebellum and other brain regions, and decreased life expectancy.