Mitochondria, Energy Production, and Sirtuins:Within the mitochondria, molecules convert into energy and then store as ATP (adenosine triphosphate). When other parts of your cells need energy, a bond breaks in the ATP molecule, releasing energy and creating ADP (adenosine diphosphate) + a phosphate molecule. Cells have anywhere from dozens to thousands of mitochondria in them, depending on the type of cell. Cells that need a lot of energy, like heart muscle cells and liver cells, have more mitochondria. The inner membrane of the mitochondria is where a lot of the magic takes place. This is where a series of reactions change the electrical potential (think energy) across the membrane. The source of chemical energy for the mitochondria is the food you eat or your own stored fat. In addition, you need ways of moving the electrons - molecules that will accept and donate electrons - across the membrane. NAD+ and FAD are the two important molecules here, which we get from riboflavin and B3. But we also need a way to turn on and off the production of the proteins needed inside the mitochondria and a way to take care of oxidative stress. That is where sirtuins come into play -- along with NAD+.
SirtuinsSirtuins are a family of seven proteins that are important in removing acetyl groups from molecules. Acetyl groups within the nucleus of the cell attach to the DNA at certain points, marking and opening up the DNA to be transcribed. They are like a chemical post-it note, pointing to what needs to be transcribed and then turned into a protein. Sirtuins remove that acetyl group at the right time, which allows the DNA to compact again and protects it from damage. The ability to turn on and off genes for transcription is what allows your body to work. But your genes also need ways to protect the DNA. Preventing damage to DNA is vital for healthy aging. (Damaged DNA can lead to cellular death or cancer.) Sirtuins are activated by NAD+ (nicotinamide adenine dinucleotide). NAD is also a vital component of mitochondrial energy production; it is elevated in response to calorie restriction. (Read more about NAD+, nicotinamide riboside, and NMN) In addition to removing acetyl groups in the nucleus, other sirtuins are active in the mitochondria and in the cytoplasm of the cell. Your mitochondria contain their own DNA which codes for a few mitochondrial-specific proteins.
SIRT3SIRT3 is a mitochondrial protein and has also been studied in regards to longevity and metabolic syndrome. It involves turning on and off several important mitochondrial genes. Higher levels of SIRT3 are connected to longevity. SIRT3 is also involved in metabolism, and a study with mice lacking SIRT3 had greater obesity and insulin resistance on a high-fat diet. The reduction of the SIRT3 function was found to lead to mitochondrial dysfunction and metabolic syndrome.[ref][ref] Researchers have found that both exposures to the cold and reducing calories upregulate SIRT3.[ref] SIRT3 function is important in preventing cancer. Mice with the gene deleted are more likely to have tumors, and human breast cancer tissue shows deletion of SIRT3 in 40% of carcinomas.[ref] A December 2014 study in Cell Metabolism found that noise-induced hearing loss in mice could be prevented with nicotinamide riboside, which is a precursor to NAD+ (nicotinamide adenine dinucleotide) and a derivative of vitamin B3. The researchers found that nicotinamide riboside activated SIRT3 in the mitochondria. This increase in SIRT3 prevented noise-induced hearing loss. Moreover, the addition of nicotinamide riboside (NR) was effective either before or after the hearing loss.[ref] Other studies show that calorie restriction slows age-related hearing loss through increasing SIRT3 "by promoting the glutathione-mediated mitochondrial antioxidant defense system."[ref][ref] One way that SIRT3 may be involved in longevity is through interaction with FOXO3, which "modulates mitochondrial mass, A/TP production, and clearance of defective mitochondria".[ref] FOXO3 genetic variants are also associated with increased longevity.
SIRT3 Genetic Variants
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