Low-calorie diet: sirtuins against aging in general and deafness in particular
Scientists have learned from nature a key path to agingLifeSciencesToday based on UW-Madison materials:
Scientists ferret out a key pathway for agingFor decades, scientists have been trying to answer the fundamental question of biology about how a low-calorie diet increases life expectancy and improves health in old age.
This fact has been confirmed on a large number of species – from spiders to monkeys. But how such a diet works at the deepest level, influencing metabolism and physiology and slowing down the steady deterioration of cells and tissues associated with aging, to a large extent, remains a mystery.
Scientists from the University of Wisconsin-Madison described the molecular pathway that plays a decisive role in the aging process in an article in the journal Cell (Shinichi Someya et al., Sirt3 Mediates Reduction of Oxidative Damage and Prevention of Age-Related Hearing Loss under Caloric Restriction). Their research not only helps explain the cascade of events that consistently contribute to this process, but also provides a rational basis for the development of drugs that can slow aging and improve health in old age.
"We are getting closer and closer to understanding what the mechanism of action of a low–calorie diet is," says Tomas A. Prolla, professor of genetics at UW-Madison and senior author of the Cell article. "This study is the first direct confirmation of the existence of a mechanism underlying the slowing down of the aging process observed with calorie restriction."
The work focuses on an enzyme known as Sirt3, one of the enzymes of the sirtuin family involved in the aging process, gene transcription, programmed cell death (apoptosis) and resistance to stress under calorie restriction. In mammals, including humans, seven sirtuins have been identified, which appear to have a versatile effect on cell fate and physiology.
The Sirt3 enzyme is less studied than other members of this family, but the new study provides "the first clear evidence that sirtuins slow down the aging process in mammals," says senior author John M. Denu.
The Sirt3 enzyme acts on mitochondria, intracellular structures that produce energy and are a source of highly reactive oxygen species – free radicals that damage cells and promote aging. In conditions of a low-calorie diet, Sirt3 levels rise, altering metabolism and leading to a decrease in the production of free radicals by mitochondria.
"There is the most direct and immediate connection between a low–calorie diet and mitochondria," says Prolla, who has been studying the effect of such a diet on the aging process and health for more than a decade. "Sirt3 plays a surprisingly important role in reprogramming mitochondria to function under conditions of metabolism changed with a low-calorie diet."
The study was conducted on mice with age-related hearing loss (AHL), a phenomenon associated with damage by free radicals to the cells of the cochlea, the structure of the inner ear that converts sound vibrations into nerve impulses. Age-related hearing loss is also characteristic of humans. Recently, this was illustrated by the fact that only very young people hear the ringing tones of ultrasonic cell phones, since the cells that pick up the highest frequencies are the first to suffer.
"Hearing loss is associated with the loss of a certain type of snail cells," notes Prolla, who established a genetic link between these phenomena in his previous work. "And hearing loss can be prevented by calorie restriction."
In accompanying experiments on cultured cells, researchers have shown that elevated levels of Sirt3 protect cells from stress and death induced by free radicals.
"The Sirt3 enzyme is sufficient to provide protection against oxidative damage," says Denu.
Although sirtuins have been widely studied for a long time, and many scientists recognize their role in aging, the new study is the first to definitively link them with slowing down the aging process in mammals.
According to Denu, understanding the molecular foundations of how enzymes that can, like Sirt3, slow down the aging process work will eventually lead to the rational development of drugs that activate their molecular pathways.
Portal "Eternal youth" http://vechnayamolodost.ru22.11.2010