Researchers: We are working on a preparation that prevents skin aging
The main mechanism responsible for cell aging is the oxidation of proteins in cells, not DNA damage, experts argue in an interview with PAP. On the basis of this discovery, they are working on a preparation to counteract skin aging.
"We biologists used to think that if a cell does not work well, the source of the problem must be in the genes. Meanwhile, our research indicates that DNA mutations are not the cause of aging, oxidation of proteins is" - says Prof. Miroslav Radman, co-founder of the Mediterranean Institute of Life Sciences (MedILS) in Split (Croatia), one of the pioneers of research on the role of proteins in aging processes.
He explains that proteins are oxidized under oxidative stress - excess reactive oxygen species (ROS) in cells. Reactive oxygen species form under the influence of UV radiation, air pollution and other stressors, but also during the process of aerobic respiration in cellular mitochondria. They cause damage in DNA as well as chemical modification of proteins - so-called carbonylation, under the influence of which proteins cease to function properly.
The problem is that while spontaneous mutations in DNA can be repaired (because cells very well-functioning repair mechanisms), protein carbonylation is an irreversible process, Prof. Radman explains.
"Carbonylation is irreparable. The only way that the cell can get rid of a carbonylated protein is to destroy it completely and replace it with a newly synthesized protein" - he explains. He adds that during the aging process, carbonylated proteins accumulate in cells at an exponential rate. There are, for example, much more of them in old skin cells than in young skin cells.
Carbonylated proteins can not perform their proper functions, for example in the DNA repair process. "Therefore, such damage to proteins contributes to a significant increase in spontaneous mutations in the cell. For example, if the frequency of protein carbonylation doubles, the percentage of spontaneous mutations in DNA increases a hundredfold" - explains Prof. Radman. For this reason, the level of carbonylated proteins is directly proportional to the percentage of dying cells. Experiments conducted by Prof. Radman`s team indicate that this applies to nematode cells, fruit fly, rodent and human cells.
Dr Francois-Xavier Pellay of MedILS explains that some proteins in cells undergo the carbonylation process more easily.
Researchers from MedILS observed in their experiments that certain small changes in the gene`s DNA (so-called gene polymorphism) causing small changes in the protein structure, also increased its susceptibility to the process of carbonylation.
Prof. Radman gave the example of a protein called alpha-synuclein, which contributes to the development of Parkinson`s disease. Studies have shown that a small change in the DNA of the gene that encodes alpha-synuclein, increases the susceptibility of this protein to carbonylation 10 times. "It affects the patient`s condition because it increases the risk of Parkinson`s disease" - explains the researcher. He adds that mutations that increase the susceptibility to carbonylation do not manifest at once, but over the course of human life, after 50-60 years.
"If we know which DNA sequence increases the risk of oxidation of a given protein, in the future it will be possible to predict the predisposition to a given disease right after birth. When it is a protein present in the kidneys, it will increase the risk of kidney disease. And similarly for proteins in other organs" - he explains.
Dr Pellay notes that the level of carbonylated proteins also increases in inflammatory skin diseases, such as psoriasis. In the future, this knowledge can help diagnose and treat psoriatic lesions.
MedilS scientists in close cooperation with researchers from the NAOS cosmetics group are now working on a preparation that will protect proteins in skin cells from carbonylation and thus counteract skin aging.
They have successfully isolated a protective protein from the bacteria Deinococcus radiodurans that live in the stratosphere (scientists catch them on the dishes when they fall with rain or snow) and are very resistant to various damaging factors, such as UV radiation or gamma radiation. "Gamma radiation causes DNA fragmentation, but these bacteria are able to quickly repair the damage. Our research shows that it is not associated with any special DNA repair method, but with the presence of a compound that protects proteins against carbonylation" - explains Dr. Pellay.
Researchers want to put the bacterial protein responsible for protection against this process in a cream to counteract skin aging. Studies carried out on various cell types suggest that it has a very strong protective effect.
According to the founder and president of the NAOS group, biologist and pharmacist Jean-Noel Thorel, this preparation may become available in about two years. The specialist says that it will represent a completely new approach to skin protection in cosmetology - that is, preventing aging instead of repairing the resulting changes. "In our opinion, prevention is much more effective and cheaper than remedial methods" - says Thorel.
But this will be only the beginning of changes that await us in cosmetology. Scientists from MedILS develop not only methods that inhibit skin aging, but also ways to rejuvenate it - also without using invasive and surgical methods.
PAP - Science in Poland
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