The old age pill: another target
The next step towards the creation of anti-aging drugsLifeSciencesToday based on the materials of the University of Michigan Health System:
Early discovery may aid search for anti-aging drugs
A group of scientists from the University of Michigan (University of Michigan) found that the suppression of a newly discovered gene increases the lifespan of roundworms Caenorhabditis elegans. Researchers studying aging have long known that a significant restriction of food intake contributes to an increase in the life expectancy of animals. But their goal is to find less radical ways by which one day it will be possible to achieve the same results in humans.
The data obtained at the University of Michigan represent the first evidence that it is quite possible to succeed in finding targets for drugs that will one day allow people to live much longer while maintaining good health.
In a study published in Aging Cell (Tsui-Ting Ching et al., drr-2 encodes an eIF4H that acts downstream of TOR in diet-restriction-induced longevity of C. elegans), scientists have established that the drr-2 gene is an important component of the key cellular pathway TOR (target of rapamycin), in which many scientists are looking for potential targets for drugs. The researchers then found that weakening or strengthening the expression of the ddr-2 gene leads to a reduction or increase in the lifespan of C. elegans, a roundworm widely used in scientific research. Exposure to the activity of the ddr-2 gene led to the same effects as a reduction or increase in the number of calories consumed.
"We have shown that in C. elegance, the ddr-2 gene is one of the main genes regulating the lifespan of the TOR pathway," says Ao–Lin Allen Hsu, PhD, researcher at the University of Michigan Geriatric Center, lead author of the study. During the experiments, it was found that ddr-2 is an analog of the human gene eIF4H (eukaryotic translation initiation factor 4H), which controls the same cell functions.
In search of possible pathways to future anti-aging drugs, many scientists around the world are focused on signaling cellular pathways sensitive to nutrient intake. The pathway studied by Xu, which is the target of rapamycin, or the TOR pathway, is so named because its activity is influenced by the drug rapamycin. Recent results of a large federal study conducted by the University of Michigan and other research centers have shown that rapamycin effectively mimics the anti-aging effects of diet restriction in mice.
Studies over the past 25 years have shown that animals, including mammals, live longer and show a less pronounced level of decline in certain aging-related indicators if they are on a limited diet. No one has yet been able to confirm that the same effect is manifested in humans, although a number of similar studies are currently being conducted.
When limiting the consumption of certain nutrients or calories, scientists note a lower level of oxidative damage in animal cells and a slower decline in the ability to repair DNA, characteristic of the aging process. It is assumed that reducing oxidative damage and slowing down the decline in the ability to repair DNA can help delay the occurrence of many age-related diseases, if not completely avoid them.
But scientists still know relatively little about why dietary restrictions lead to such effects. Over the past 10 years, some progress has been made in identifying genes and their corresponding proteins, the activity of which is suppressed when nutrition is restricted. Therefore, a deeper understanding of the processes associated with such suppression may help researchers find targets for drugs that can delay aging without the need to restrict diet.
Drugs designed to suppress certain genes or proteins that are components of nutrient-sensitive cellular pathways will be much more attractive than restricting a diet. It is believed that to slow down the aging process, you need to reduce the amount of food by 30-40 percent – a gloomy prospect. Moreover, such drugs can be developed taking into account certain undesirable effects inevitably associated with such a level of dietary restriction, for example, a decrease in the ability to procreate.
C. elegans is a tiny round nematode worm whose lifespan of just 2 weeks is a great advantage for scientists studying aging. A transparent worm with a length of 1 millimeter has other valuable features for scientists. It demonstrates many of the aging-related changes observed in higher organisms.
"Many of the genes that control the rate of aging of C. elegans have been preserved during evolution, which means that other animals also have them. And many very similar to them are found in the human body," says Xu.
Xu and his colleagues have created various mutant strains of roundworms, some with the silent ddr-2 gene, others with its overexpression. They wanted to find out whether ddr-2 inactivation is important for the effect of the TOR cellular pathway on life expectancy, and received a positive response. Other newly discovered genes also have an effect on the TOR signaling network. But researchers have managed to find a promising key to anti-aging drugs of the future, proving that to make worms live longer than their wild-type relatives used as controls, it is enough to suppress only one ddr-2 gene.
"It is known that the reduction of signaling in the TOR cellular pathway in response to changes in the environment or to genetic influences involves a cascade of cellular signals that alter growth, metabolism and protein synthesis, and reduces the rate of aging," says Xu. "Our latest study has shown that the ddr-2 gene may play a key role in the TOR signaling network for the regulation of protein synthesis, and, accordingly, life expectancy."
Portal "Eternal youth" http://vechnayamolodost.ru01.09.2010