29 January 2018

Age-related aging of the immune system (3)

Between the death of immune cells and the activation of cytokine synthesis

Immuno senescence in aging: between immune cells depletion and cytokines up-regulation Maria Teresa Ventura et al., Clinical and Molecular Allergy, 2017.

Translated by Evgenia Ryabtseva
The beginning of the article is here.
For links, see the original article.

Oxidative damage

Another factor affecting the state of the immune system, in addition to the antigenic stimulus, is the effect of metabolites (active forms) of oxygen. Given their ability to cause serious damage, it is quite plausible to assume that aging is also caused by the accumulation of free radicals. An increase in the concentration of oxygen metabolites and their accumulation leads to damage to important cell components (lipid membranes, structural proteins and enzymes, as well as nucleic acids), the appearance of which is hindered by enzymatic and non-enzymatic defense systems, enzymes that repair damage, as well as DNA damage mechanisms and damage-induced apoptotic processes. These protective mechanisms lose their effectiveness as a result of constant exposure to oxidative stress and the accumulation of mutated and entered the phase of physiological aging of cells, which leads to an increased risk of cancer. The p53 protein prevents the development of neoplasms by triggering the reaction of cells to damage (repair of DNA damage or, in case of failure, apoptosis). This protein plays an important role in physiological aging: an increase in its expression is accompanied by a decrease in the frequency of neoplasms, at the same time, on the other hand, it increases the rate of aging. As a result, a delicate balance is formed between a decrease in the level of p53, leading to death from cancer, and an increase in the level of p53, leading to death from premature physiological aging. Moreover, overexpression of p53 promotes the production of intermediate forms of oxygen.

Mitochondria are an important source of intermediate oxygen forms. Despite the fact that their main function is to produce energy, isolated mitochondria generate oxygen radicals in the process of oxidative phosphorylation. The mitochondrial electron transfer chain is imperfect, as it produces a superoxide radical. Enzymatic dismutation of the superoxide radical leads to the production of hydrogen peroxide (H2O2), another important biological oxidant. Another factor contributing to physiological aging is apoptosis, especially induced by acidic metabolites – by-products of the activity of the enzymes lipoxygenase and cyclooxygenase. However, it is unclear whether these products induce the synthesis of reactive intermediates or whether they directly induce apoptosis by acting as antioxidants. Another intermediate product of oxygen metabolism is nitric oxide, a free radical known as an important regulator of mitochondrial function, capable of not only activating the phenomenon of apoptosis, but also, in physiological concentrations, preventing apoptosis and interfering with the capsaicin signaling cascade. In general, high doses of oxidants can change the redox potential, reducing ATP levels and increasing the porosity of membranes, which leads to the progression of the phenomenon of aging of cells, including cells of the immune system.

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