17 October 2022

The benefits of "zombie cells"

According to a new study by the University of California, San Francisco, not all aged cells are harmful and should be destroyed to prevent age-related diseases. Some of them contribute to normal recovery after damage to young tissues.

Old cells can both damage and heal

At first, the old cells were considered only as harmful. With age, people accumulate cells that have the characteristics of old worn-out cells, including the inability to divide. They do not die as they should, but continue to live, releasing a cocktail of inflammatory factors that are associated with Alzheimer's disease, arthrosis, cancer and other age-related diseases. The catchy name "zombie cells" was invented for them.

Senolytics are aimed at zombie cells, thanks to them, researchers have made an exciting discovery: the removal of old cells in animals prevents or weakens age-related diseases and increases life expectancy. This was followed by a boom in activity in research laboratories and pharmaceutical companies focused on finding and improving these drugs.

But, as a new study has shown, the destruction of zombies brings both benefits and harm – aging cells have the ability to accelerate normal healing by activating stem cell repair.

Studying zombie cells

The main difficulty in studying aging cells is that they are difficult to detect, since biomarkers of aging (including oncosuppressor p16) are quite rare. Researchers had to extract fibroblasts and cultivate them so that they could grow and produce enough cells for experiments. Then they were exposed to chemicals that accelerate aging. But in living organisms, cells interact with surrounding tissues, which greatly affects the activity of genes.

This means that the characteristics of cells growing in isolation in a glass container may differ greatly from the characteristics of cells in their natural habitat.

To create a more powerful tool for their research, Dr. Reyes de Barbosa and her colleagues have perfected a common technique of merging the corresponding gene – in this case, the p16 gene, overly active in aging cells – with a green fluorescent protein as a marker that will help determine the location of cells under the influence of ultraviolet light.

By increasing the amount and stability of green fluorescent protein in these aging cells, Reyes significantly enhanced the fluorescent signal, which finally allowed the researchers to see zombies in their natural habitat – living tissues.

Zombies stimulate stem cells shortly after birth

Using this highly sensitive tool, the researchers found that aging cells exist in young and healthy tissues to a greater extent than previously thought, and actually begin to appear shortly after birth.

Scientists have also identified specific factors that secrete aging cells, stimulating stem cells to grow and repair tissues.

An interesting observation was made by the authors: immune system cells (macrophages, monocytes) can activate zombie cells in old or damaged tissues, and those, in turn, increase inflammation, which is a critically important modifier of cell activity and regeneration.

In their studies of lung tissue, the group observed green-colored zombie cells next to stem cells on the basement membrane, which serves as a barrier preventing foreign cells and harmful chemicals from entering the body, and also allows oxygen from the air in the lungs to penetrate into the underlying tissues. Damage may occur on this dynamic surface.

The team found aging cells in a similar position in other barrier organs, such as the small and large intestine and skin, and experiments confirmed that if senolytics destroy aging cells, lung stem cells cannot properly restore the barrier surface.

The results of the study highlight the need to develop better drugs that will target specific subsets of aging cells involved in disease rather than regeneration.

Article by N.Reyes de Mochel et al. Sentinel p16INK4a+ cells in the basement membrane form a reparative niche in the lung is published in the journal Science.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru According to Neuroscience News: Scientists Reappraise the Role of 'Zombie' Cells That Anti-aging Medicine Has Thought to Eliminate.

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