21 April 2015

Genetic indicator of aging

Scientists have created a "clock" to assess genetic aging


Scientists from MIPT and their colleagues from the Institute of Biology of the KNC RAS in Syktyvkar have created a simple and reliable method for assessing genetic "breakdowns" associated with aging – these "clocks" will allow, in particular, to conduct long-term studies to assess the effectiveness of drugs that slow down aging. The results of the study were published in the journal Mutation Research (Velegzhaninov et al., Age dynamics of DNA damage and CpG methylation in the peripheral blood leukocytes of mice).

Aging of the body is always accompanied by the accumulation of damage in DNA molecules and a decrease in the effectiveness of their self-healing. These two factors lead to a general deterioration of the work of the genetic apparatus and cells in general. Numerous studies have shown that with age, the number of DNA damage associated with exposure to aggressive oxygen compounds – free radicals, in particular, breaks in the strands of molecules, increases.

At the same time, the experimental results showed that the number of certain types of damage varies greatly. For example, a study of human leukocytes showed a five-fold difference in the ability to repair DNA. In addition, most studies of aging-related processes were conducted on tissues obtained after the death of the body.

"Scientists need biomarkers to assess genetic damage that could be tracked on a living organism, without complex operations and for a long time," says the study's lead author Alexey Moskalev, head of the Laboratory of Aging Genetics and Life Expectancy at the MIPT Center for Living Systems.

He and his colleagues developed a combined indicator of genetic processes associated with aging, which they called DDLD (DNA Damage Level Differential, the differential of the level of DNA damage). It takes into account several types of damage: the proportion of purine bases damaged by free radicals (the building blocks of DNA), the number of breaks in both strands of the DNA molecule, as well as the level of methylation – the proportion of genome elements "turned off" by methyl groups.

Scientists evaluated this index in "combat conditions" – in an experiment on 144 mice aged 38 to 709 days. Peripheral blood samples were taken from animals (in mice they are taken from the tail, not from the fingers, as in humans), and then the samples were examined, analyzing the indicators included in the DDLD indicator.

As expected, the level of damage to DNA molecules in the blood cells of mice increased with age, while the DDLD index made it possible to accurately assess the level of genetic aging of mice, although it did not allow predicting the remaining life time: it depends on a combination of various factors, including those still unknown, and not only on the level of genetic damage.

"Our method will allow us to evaluate the effectiveness of different types of geroprotectors, to study the impact of environmental factors, stress on the rate of aging," Moskalev notes.

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