Molecular interaction modeling reveals an enzyme that can reverse natural
Cells are damaged in response to factors such assuch as oxidative stress, DNA damage and telomere shortening. This process - cellular aging - is important for the human body. It prevents damaged cells from multiplying and turning them into cancerous ones. But the same process leads to aging of the body and age-related diseases. Scientists have long been trying to reverse this process. But the methods used so far impaired tissue regeneration and caused malignant formations.
Professor Kwang-Hyun Cho from KAIST and colleaguesused a novel strategy to identify molecules that may help reverse the process of cellular aging. Using algorithms, their research, and open databases, the scientists developed a model that simulates the interactions between these molecules. The analysis made it possible to predict which molecules will help in the fight against cellular aging.
Then they examined one of the molecules, the enzymePDK1, in incubated senescent skin fibroblasts and 3D skin-equivalent tissue models. They found that blocking PDK1 leads to inhibition of two downstream signaling molecules. This, in turn, restores the ability of cells to return to the cell cycle rather than leaving it after damage. At the same time, the cells retained the ability to regenerate. Moreover, their reproduction did not lead to malignant transformation.
Scientists recommend furtherstudies of organs and organisms to determine the full effect of PDK1 inhibition. Since the gene encoding PDK1 is overexpressed in some cancers, scientists hope that suppressing it will have both anti-aging and anti-cancer effects.
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