How to protect DNA from aging
The assault on the fortress "Aging process" continues: scientists have found a way to preserve DNA
NanoNewsNet based on URMC materials: Scientists Find a Key to Maintaining Our DNADNA contains all the genetic instructions that make us who we are, and preserving its integrity throughout life is the most important, but also the most difficult task solved by the body in the process of its aging.
Having taken the first but important step in studying these processes, scientists have discovered how the process of DNA replication and repair is regulated, outlining the prospects for such an intervention that can improve the natural preservation of genetic information.
The new discovery could help scientists delay the onset of aging and the development of age-related diseases by limiting the loss and damage to our genome, making us more susceptible to the development of cancer and neurodegenerative diseases such as Alzheimer's disease. Keeping our DNA intact in old age can help save us from the weakness and suffering that go hand in hand with the aging process.
"Our research is at a very early stage, but there is a huge potential in it," says its head, Robert Bambara, PhD, head of the Department of Biochemistry and Biophysics at the University of Rochester Medical Center.
In the Journal of Biological Chemistry (Eukaryotic Lagging Strand DNA Replication Employs a Multi-pathway Mechanism That Protects Genome Integrity), Bambara and his colleagues report that the preservation of our DNA depends on a process called acetylation. Scientists have discovered that acetylation determines the degree of accuracy of both replication and DNA repair.
The discovery is based on an earlier study in which it was found that in the process of human evolution, two ways of DNA replication and repair have developed – a standard way that eliminates some damage and a certain number of errors, and an "elite way" that corrects most of them.
Only a small part of our DNA, which controls the creation of all the proteins of our body – proteins of blood cells, heart, liver, etc. – follows an elite path that uses much more energy and therefore costs the body much more. The remaining, most of our DNA, which is not involved in the process of protein synthesis, follows a standard path that requires less resources and proceeds at a higher speed.
However, scientists have never understood what controls which of the paths a particular DNA fragment will follow. The authors of the latest study found that, like a policeman controlling traffic at a busy intersection, the acetylation process determines which of the paths certain proteins will take, preferring to protect the DNA that creates proteins and directing such fragments along a more precise elite path.
"If we find a way to improve the protection of DNA involved in protein synthesis, essentially improving what our body is already doing by eliminating errors, we can live longer," says Lata Balakrishnan, a researcher at the Medical Center. "A drug that causes a small change in this acetylation-based regulatory pathway will be able to delay the development of cancer or neurological diseases and will allow us to go far beyond the current human lifespan."
"It is clear that a simple preventive approach will be the key, of course, not to immortality, but to a longer life without diseases," Bambara adds.
DNA replication is a complex and error–prone process that occurs when our cells divide and our DNA duplicates. Duplicated copies of DNA first consist of individual fragments, which should later combine to create a new complete DNA chain. The first half of each individual DNA segment usually contains most of the errors. The appearance of errors in the second half of the segment is less likely.
In the DNA following the standard path, the first 20 percent of each individual segment of it is marked, cut out and removed. This empty space is then filled with a subsequent part – a more precise section – of the adjacent DNA when two of its segments form a complete chain.
In contrast, DNA following the elite path receives a special "treatment": the first 30-40 percent of each individual segment is marked, deleted and filled in, which means that more errors are eliminated before the segments are combined. The end result is a more accurate copy of the DNA.
The same situation is observed in the process of DNA repair, when the body removes its damaged areas.
Bambara's group is now further studying the newly discovered acetylation-controlled regulatory process in order to understand how it can be interfered with and strengthen the natural protection of important genetic information. To determine how the joint work of cellular proteins causes acetylation, which adds a certain chemical (acetyl group) to the proteins involved in the process of DNA replication and repair, they study the cellular systems of humans and yeast. Scientists affect cells in various ways, damaging them or making genetic changes, and find out in which direction these changes affect acetylation.
Humans have developed two ways of DNA replication and repair
– standard, fast and less accurate,
and "elite", high-precision and slower
(picture: urmc.rochester.edu )
Although it is still a long way from determining chemical compounds or testing existing drugs that can affect the acetylation process, they are confident that this research has a future.
"Today, the time between the initial discovery and the development of a drug is significantly reduced. I would suggest that a therapeutic drug that can help us live longer and stay healthy may appear in 25 years," Bambara estimates the prospects.
Portal "Eternal youth" http://vechnayamolodost.ru22.03.2011