11 October 2022

How the kidneys age

Scientists have proved for the first time that the number of stem cells in the kidneys decreases with aging

RNF Press Service

Russian scientists have established for the first time that the number of stem cells in the kidneys decreases with age. At the same time, aging stem cells gradually lose their ability to divide, as well as their resistance to damaging factors. This can lead to the deterioration of kidney function and an increased risk of developing chronic diseases in the elderly. The results of the study, supported by a grant from the Russian Science Foundation (RNF), are published in the International Journal of Molecular Sciences (Buyan et al., Age-Associated Loss in Renal Nestin-Positive Progenitor Cells).

There are about a hundred trillion cells in an adult human body, which is five hundred times more than the stars in our galaxy. The cellular composition is constantly changing: old, poorly functioning cells are replaced by new ones. At the same time, in organs such as the heart, intestines and muscles, the number of cells is maintained at a relatively constant level. Populations of resident, that is, stem cells located in the organ itself that retain the ability to divide, are responsible for this. So, each of them is divided into two — one "follows in the footsteps" of the mother and supports a pool of stem cells, and the other differentiates into mature cells that form tissues and organs.

Scientists from the A.N. Belozersky Institute of Physico-Chemical Biology of Lomonosov Moscow State University (Moscow), the Faculty of Bioengineering and Bioinformatics of Moscow State University (Moscow) and the V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology (Moscow) have found that the number of renal stem cells decreases with age. The population of these cells differs from other cells in the kidneys by the presence of a marker protein - nestin. The authors used transgenic mice in whose cells nestin is synthesized simultaneously with a green fluorescent label, and with its help tracked how many resident stem cells mice of different ages had — twenty-one days and one year. The results of histological analysis showed that in the kidney tissue preparations of old animals there were almost five times fewer cells with nestin and a luminous label than in the tissue preparations of young animals.


Kidney slices of transgenic mice, where stem cells fluoresce with green light due to the expression of green fluorescent protein. Source: Egor Plotnikov.

Using cells from the kidney tubules of mice, the researchers also showed that the rate of their division in culture decreases with aging. A small number of young cells form a uniform layer at the bottom of the culture vial on the third day, while old ones in the same amount form only on the fifth.

In addition, it turned out that cell cultures from the kidneys of old animals, compared with young ones, lose their resistance to damaging factors. With a lack of oxygen and glucose, cell death occurred in both age groups, but the young survivors recovered faster after stress. Under the influence of the antitumor drug cisplatin, which negatively affects healthy tissues, reactive oxygen species were synthesized in the culture of old cells, whereas this did not happen in the culture of young cells. In addition, the functioning of mitochondria was disrupted during aging, which can affect their energy production.

"During the study, we were the first in the world to show that the number of resident stem cells in the kidneys decreases sharply with age. This reduces the resistance of the kidney tissue to damaging factors and increases the risk of developing diseases, as well as slows down the recovery of the kidneys during recovery," says Marina Buyan, a student of the Faculty of Bioengineering and Bioinformatics of Moscow State University.

"We plan to develop compounds that improve the recovery of kidney tissue. The study of such drugs will be a big step in the treatment of kidney diseases, as well as ways to maintain the normal functioning of these organs in the elderly," says Nadezhda Andrianova, Candidate of Biological Sciences, researcher at the A.N. Belozersky Institute of Physico—Chemical Biology of Moscow State University.

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