Sirtuins prolong life, but damage neurons

Scientists at the University of Southern California, working under the guidance of Dr. Walter Longo, argue that in some cases, overexpression of proteins of the sirtuins family (sirtuins, Sir2), known for their ability to slow aging, causes oxidative damage to brain cells.

Sirtuins have been identified in many organisms, ranging from bacteria to humans. According to the results of earlier studies, they control the aging processes in roundworms Caenorhabditis elegans and fruit flies.

There is evidence of the involvement of Sir2 proteins in life-prolonging mechanisms associated with calorie restriction in a number of organisms (but not all). In addition, the authors demonstrated that the absence of sirtuins in yeast cells further prolongs the life of "starving" cells.

SirT1, a variant of Sir2 found in mammalian cells, is involved in the management of a variety of physiological processes, including glucose metabolism, DNA damage repair and cell death. It also regulates the activity of a number of factors involved in the formation of stress reactions.

According to the results of the work of the Longo group, rat neurons in cell culture are much more likely to survive exposure to compounds that induce oxidative stress if a SirT1 inhibitor is added to the nutrient medium.

In the brains of living genetically modified mice with the SirT1 gene knocked out, the level of oxidative stress was lower than in mice with normal synthesis of this protein. But the lifespan of mice without the SirT1 gene was shorter than that of normal mice, regardless of the caloric content of the diet.

The results obtained indicate that SirT1, like its analogue Sir2 in yeast cells, has a pro-oxidative function. However, they confirm that sirtuins perform both positive and negative roles. Based on the data obtained, Longo warns that the development of SirT1-stimulating drugs for clinical use is still very premature, because it is still necessary to obtain convincing evidence of the safety of their long-term use.

Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of ScienceDaily

09.07.2008