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Restoring Protective Mechanisms in the Aging Kidney

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Restoring Protective Mechanisms in the Aging Kidney

Accumulation of lipid degradation products, cell membranes and organelles in aging kidney cells as a result of ineffective autophagy (microphotography). Credit: Lomonosov Moscow State University
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Researchers from Moscow State University studied the influence of aging on key cellular processes, which has implications for the treatment of renal failure. 

The study was published in Cell Cycle, and focused on autophagy, the functioning of mitochondria and oxidative stress.

Autophagy is the process by which cells destroy and process their damaged components. In this process, the cell is self-cleaning from unnecessary organelles, and sometimes "self-eaten" entirely. With the help of this adaptive mechanism, a healthy phenotype is maintained at the cellular level.

Autophagy is activated in certain types of acute renal failure (for example, caused by taking antibiotics or anti-cancer drugs), as well as with sepsis and kidney ischemia.

Scientists already know that the activation of autophagy reduces the severity of kidney damage.

However, the effectiveness of autophagy decreases with aging, and although the number of lysosomes (organelles digesting damaged cellular components) in old cells even increases, they do not cope with their function. In such cells, there is an accumulation of oxidized proteins and damaged organelles.

In the international base of scientific publications on medicine PubMed more than 3,000 articles are devoted to the research of aging of the kidney.

However, less than 10 of them are related to the effectiveness of therapy for acute renal failure in the elderly.

Scientists from the Research Institute of Physico-Chemical Biology named after A.N. Belozersky MSU examined renal pathologies that accompany the aging of the body. First of all, it is acute renal failure, which occurs in people older than 60 years several times more often.

"In our article we showed that aging is associated with the accumulation of damaged biological structures in the kidney (proteins, lipids, nucleic acids, organelles). The replacement of the "young" (healthy) phenotype with the "old" phenotype occurs at a time when a certain threshold value of such changes is reached, "said Yegor Plotnikov, a leading researcher at the Institute of Nuclear Research of the Moscow State University, Doctor of Biological Sciences.

One of the effective strategies used to combat the changes associated with aging is the restriction of diet (saloricrestriction or dietrestriction - unloading-dietary therapy).

It activates the processes of autophagy and reduces age-related pathological changes in the kidney. Although the most effective experiments have shown the approaches in which the restriction of nutrition is used throughout life, some studies have shown that a short-term reduction in food intake (by 30-40% in a few weeks) can increase the resistance of the kidney to the development of acute renal failure.

In addition to the systemic physiological approach to treatment, pharmacological preparations imitating caloric restriction (for example, rapamycin) are sometimes used, but its effectiveness for the treatment of the old kidney has not yet been proven.

Another approach to protecting the kidney is mitochondrial-targeted therapy. Since in acute kidney failure even in cells of young organisms mitochondria are severely damaged, and aging itself leads to a violation of mitochondrial functions, the idea of influencing mitochondria to prevent damage to the kidneys of old organisms looks very attractive.

Among the compounds that have proved effective in experimental models, mitochondria-directed antioxidants, such as mito TEMPO, SS-31 peptides (Bendavia), and compounds of the SkQ group developed at the MVLomonosov Moscow State University are primarily distinguished.

"Unfortunately, research is now dominant, in which various therapeutic approaches to protecting the kidneys are being tested on young animals. There are much fewer works studying changes in the kidneys of old animals. Moreover, there are practically no works dedicated to the targeted protection of the kidney in an aging organism. We propose to fill this gap not only through experiments on old animals, but also by analyzing the data of clinical studies, "the scientist commented.

Currently, the effectiveness of drugs in a clinical study is often averaged between different age groups. A more personalized approach would reveal key differences in kidney physiology in elderly patients and create drugs that affect precisely the signaling pathways that will be effective in this group of patients.

This article has been republished from materials provided by Lomonosov Moscow State University. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference:


Jankauskas, S. S., Silachev, D. N., Andrianova, N. V., Pevzner, I. B., Zorova, L. D., Popkov, V. A., . . . Zorov, D. B. (2018). Aged kidney: Can we protect it? Autophagy, mitochondria and mechanisms of ischemic preconditioning. Cell Cycle, 1-19. doi:10.1080/15384101.2018.1482149 

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