Biology

Cellular Damage Drives the Aging of the Kidney

The SENS view of aging is a synthesis of decades of evidence produced by the research community. It is that aging is caused at root by an accumulation of molecular damage in and around cells, damage that occurs as the result of the normal operation of cellular metabolism. The logical approach to aging is therefore to repair this damage, but, sad to say, only a small fraction of the research community pursues work of this nature.

Why is this case? Perhaps because the dominant paradigm of investigative research involves picking one age-related disease and then working backwards from the disease state, trying to uncover contributing factors that occur in the final stages of the progression of disease. The first opportunities to produce therapies as a result of increased understanding therefore involve changes in cells and tissue that are far downstream of the root causes of aging, have limited relevance to aging beyond the specific disease, and offer only limited potential benefits. It is not the right path forward if we want to see meaningful progress in our lifetimes.

Autophagy is a process of destruction and processing of damaged cell components by the cells themselves. It is used by a cell to clean itself of excessive organelles and sometimes for programmed cell death. This adaptive mechanism supports a healthy phenotype on the cellular level. Autophagy is activated in certain cases of acute kidney failure (e.g., caused by the administration of antibiotics or anti-cancer drugs), sepsis, or kidney ischemia. Scientists already know that it is the activation of autophagy that reduces kidney damage manifestation.

However, while an organism is aging, the efficiency of autophagy declines as well. Though the number of lysosomes (the organelles that digest damaged cell components) is increased in old cells, they fail to perform their function. Oxidized proteins and damaged organelles (including mitochondria that participate in the respiration and energy production) start to pile up.

A team of scientists considered kidney pathologies that accompany aging – first of all, acute kidney failure that is several times more likely to be observed in patients over 60. “In our article we demonstrated that aging is associated with the accumulation of damaged biological structures (proteins, lipids, nucleic acids, organelles) in the kidney. The replacement of a young (healthy) phenotype with an old one takes place when a certain threshold level of such changes is reached.”

Link: https://www.eurekalert.org/pub_releases/2018-08/lmsu-msu081018.php

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