Over time, the body’s cells stop working properly and begin to accumulate, which eventually leads to tissues aging. During a person’s life, cells undergo various types of stress, such as solar radiation, which leads to them accumulating mutations. The body activates defense mechanisms at a certain point in order to prevent a tumor from developing: either the cell ‘commits suicide’ or it becomes senescent, which is a kind of ‘zombie’ state between life and death, in which it no longer functions despite still being alive, and it also begins to manufacture products that replicate the zombie state in the other healthy cells around it. While the organism is young, the immune system can eliminate these cells and clean up the tissues. However, as people get older, the immune system stops performing this maintenance; the reasons why this happens are unknown. This means that these zombie cells begin to accumulate in our tissues, impairing how they work, and leading to aging.
Studies in animals have shown that with the administration of drugs called senolytics, which are able to eliminate these old cells, it is possible to improve the life expectancy and quality of life of animals. Researchers at the UOC collaborating with the University of Leicester (United Kingdom) have discovered a new molecule that is able to destroy these old cells without affecting the healthy ones. This paves the way to being able to delay the aging of the body’s tissues and eventually, to improving quality of life and life expectancy in human beings. For now, the results have been obtained in cells in vitro, and testing with animal models will now begin.The researchers, led by Professor Salvador Macip, dean of the UOC’s Faculty of Health Sciences and Professor of Molecular Medicine at the University of Leicester, have identified a molecule called CUDC-907 that destroys old cells quite efficiently and specifically, with few side effects on healthy cells.
In cancer, this drug acts by inhibiting two cell communication pathways: the PI3K pathway and the histone deacetylation process driven by histone deacetylases (HDACs). The first is used by mitogenic signaling induced by growth factors and hormones; it also hsa suppressive activity against programmed cell death (apoptosis), which malignant cells cousl undergo once they have been exposed to radiotherapy or chemodrugs. Histone deacetylation, instead, is a nuclear process that suppresses gene expression driven by its opposite process (acetylation) and operated by acetyltransferases (HATs). The drug, whose other name is Fimepinostat, has already been explored in clinical trials: it demonstrated efficacy in a phase 1 study of patients with relapsed/refractory diffuse large and high-grade B-cell lymphomas, and cancers like pancreatic carcinoma, hepatic carcinoma, esophageal carcinoma and small cell lung cancer.
In this study, the researchers used different models of human cancer cells, and found that Fimepinostat eliminates a specific type of senescent cell with limited side effects. They will now begin tests with animal models, and if they obtain good results, they will then test it with humans. Professor Macip, senior leader of the research, commented: “The drug we identified is a powerful destroyer of old cells and its effect against some cancers is also now being investigated, so it could have a double effect: anti-cancer and at the same time, it could act against old cells that make the cancer reappear. This drug could be administered with chemotherapy or radiotherapy to destroy these zombie cells and by doing so, considerably reduce cancer relapses. The drug could also be applied in diseases where the accumulation of senescent cells plays a role, such as Alzheimer’s disease Perhaps an intensive dose of the drug would clean the brain and prevent the disease from progressing”.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
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