Apoptosis against cholesterol plaques

Cellular cleansing saves from atherosclerosis

Kirill Stasevich, "Science and Life"

Many diseases arise because of our own aged cells, which either can no longer perform their functions at all, or continue to do something, but incorrectly, not in the right way. The fact that a cell has aged can be understood by the state of its DNA, in which more and more damage and errors accumulate over time – intracellular DNA repair systems simply do not have time to cope with them.

Usually, in this case, the cell immediately stops dividing – otherwise, with a whole "bouquet" of mutant genes "on hand", there is every chance of turning into a malignant one and giving rise to a cancerous tumor. But even after stopping division, the old cell continues to live in the body, synthesize some molecules, isolate them from itself into the external environment. Moreover, such molecules are capable of causing trouble to the surrounding normal cells and tissues.

Over time, the number of cells that are "neither alive nor dead" in the body only increases, but if you get rid of them, it literally helps to improve the body and increase life expectancy. You can get rid of them by turning on apoptosis, or a program of cellular self-destruction.

At the beginning of the year, we wrote about the experiments of Darren J. Baker and his colleagues from the medical college at the Mayo Clinic, who injected middle–aged mice with a drug that stimulates apoptosis, and thereby achieved purification from 50%-70% of old cells - after cellular cleansing, mice became healthier, their kidneys worked better and the heart, and most importantly, they lived 20% longer.

In a new paper published in Science (Childs et al., Senescent intimate foam cells are deleterious at all stages of atherosclerosis), the same researchers analyze in more detail how cell cleansing reduces the likelihood of atherosclerosis. As we know, with atherosclerosis, plaques are formed on the walls of blood vessels, consisting of lipids and various cells (immune, muscle, connective tissue), which gradually grow, and increasingly close the lumen of the vessel, impairing the blood supply to one or another part of the body (what happens if such a plaque blocks the vessel that feeds the heart, it is not necessary to explain it is necessary). It is believed that the risk of atherosclerosis increases if there is too much fat.

In the experiment, genetically modified mice were used, in which, in aged cells, it was possible to launch a program of cellular suicide – apoptosis from the outside. A special substance interacted precisely with such half-working cells and turned the molecular "switch" that triggered cellular self-destruction.

The animals were kept on a fat-enriched diet for three months, then apoptosis was started in some of them, and the condition of the vessels was monitored. Signs of atherosclerosis in mice appeared quite soon, on the ninth day after their transition to fatty foods. But in those mice that were cleaned of old cells, atherosclerotic plaques appeared 60% less often – which is understandable, since the deposits on the walls of the vessels were rich in aged cells. Among them, the most dangerous were immune macrophages, which absorbed a lot of fat and included inflammation, because of which the plaque began to grow.

In the later stages, the same "obese" macrophages secrete enzymes that make the plaque brittle, brittle, so that a piece can come off from it, float somewhere with blood and eventually clog some vessel. By the way, in the case when atherosclerotic plaques were still formed in mice after the destruction of old cells, they, nevertheless, were stronger, and the probability that they would break, come off, and clog something somewhere remained small.

In the future, the authors of the work want to double-check their results on other animals whose cardiovascular system is more similar to a human one. It is too early to talk about clinical prospects here: although apoptosis – a program of cellular self–destruction - should be included primarily in aged cells, it is necessary to make sure that when we stimulate apoptosis from the outside, using pharmacological methods, it will affect only old cells, and more or less young and healthy ones remain alive and working.

Portal "Eternal youth" http://vechnayamolodost.ru  31.10.2016