‘Zombie cells’ are still alive but can’t function, and they accumulate as we age

According to our study recently published in Structural and Molecular Biology of Nature.

When cells prepare to divide, their DNA is tightly wrapped around proteins to form chromosomes that provide structure and support for genetic material. At the ends of these chromosomes are repeating segments of DNA called telomeres that form a protective cap to prevent damage to genetic material.

However, telomeres shorten each time a cell divides. This means that as cells divide more and more as you age, your telomeres become shorter and more likely to lose their ability to protect your DNA.

Damage to genetic material can lead to mutations that cause cells to divide uncontrollably, leading to cancer.

However, cells avoid becoming cancerous when their telomeres become too short after dividing too many times and risk accumulating damage along the way, entering a zombie-like state that prevents cells from dividing by a process called cellular senescence.

Because they resist death, senescent cells – or “zombies” – accumulate with age. They may benefit health by promoting senescence of neighboring cells at risk of becoming cancerous and by attracting immune cells to eliminate cancerous cells.

But they can also contribute to disease by impairing tissue healing and immune function, and by secreting chemicals that promote inflammation and tumor growth.

We wanted to know if direct telomere damage might be enough to trigger senescence and make zombie cells. To understand this, we had to limit the damage to only telomeres.

So we attached a protein to the telomeres of human cells grown in the lab. Then we added a dye to the protein that makes it sensitive to light.

Shining far-red light (or light with a slightly shorter wavelength than infrared light) on cells prompts the protein to produce oxygen free radicals – highly reactive molecules that can damage DNA – directly at the telomeres, sparing the rest of the chromosome and the cell.

We found that direct damage to telomeres was sufficient to turn cells into zombies, even when these protective caps were not shortened. We found that the reason for this was likely the result of disrupted DNA replication at the telomere level, which makes the chromosomes even more susceptible to damage or mutation.

why is it important

Telomeres naturally shorten with age. They limit the number of times a cell can divide by signaling cells to become zombies when they reach a certain length.

But an excess of free radicals produced both by normal bodily processes and by exposure to harmful chemicals like air pollution and tobacco smoke can lead to a condition called oxidative stress that can accelerate telomere shortening. .

This can trigger senescence prematurely and contribute to age-related diseases, including immunodeficiency, cardiovascular disease, metabolic disease, and cancer.

Our study reveals that telomeres serve not only as alarm clocks that indicate a cell has been divided too many times, but also as alarm bells for harmful levels of oxidative stress. Age-related telomere shortening isn’t the only thing that triggers senescence; telomere damage is also enough to turn a cell into a zombie.

What other research is being done

Researchers are investigating treatments and interventions that can protect telomeres from damage and prevent the buildup of zombie cells. A number of studies in mice have shown that eliminating zombie cells can promote healthy aging by improving cognitive function, muscle mass and function, and recovery from viral infections.

Researchers are also developing drugs called senolytics that can either kill zombie cells or prevent them from growing in the first place.

And after

This study focuses on the consequences of telomere damage in actively dividing cells, such as kidney and skin cells. We are now looking at how this damage will manifest in cells that are not dividing, such as neurons or heart muscle cells.

While researchers have shown that telomeres in nondividing cells and tissues become more dysfunctional with age, it’s unclear why this happens when those telomeres shouldn’t be shortening in the first place.The conversation

Patricia Opresko, Professor of Environmental and Occupational Health, Pittsburgh University of Health Sciences and Ryan Barnes, Postdoctoral Researcher in Environmental and Occupational Health, Pittsburgh University of Health Sciences.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Leave a Comment