A "mortality timer" found in the human body

Researchers from Weill Cornell Medical School (New York, USA) have found a "mortality timer" in the human body. They claim that the secret of cellular youth may lie in the preservation of the small nucleus, a dense structure in the cell nucleus.

These findings were discovered in yeast, a model organism known for its role in making bread and beer, but surprisingly similar to humans at the cellular level. The new study, published in Nature Aging, could lead to new longevity treatments that could extend human life span, ScitechDaily writes. It also sets a mortality timer that shows how much time a cell has left before it dies.

Cellular aging

With age, people are more likely to develop diseases such as cancer, cardiovascular, and neurodegenerative diseases.

"Aging is the highest risk factor for these diseases. It also sets a mortality timer that shows how much time a cell has left before it dies. Instead of treating each disease individually, a better approach would be to develop a therapeutic or supplement that would delay the onset of the diseases by preventing the underlying molecular defects that cause them," says Dr. Jessica Tyler, professor of pathology and laboratory medicine at Weill Cornell Medicine.

The nucleus may contain a key

The nucleus contains the chromosomes of the cell and the nucleolus, which contains the ribosomal DNA (rDNA). The nucleus isolates the rDNA, which encodes the RNA parts of ribosomes, the mechanisms for building proteins. rDNA is one of the most fragile parts of the genome because its repetitive nature makes it difficult to maintain and repair if damaged. If rDNA damage is not precisely repaired, it can lead to chromosomal rearrangements and cell death.

In organisms ranging from yeast to worms to humans, nuclei grow larger during aging. On the other hand, anti-aging strategies, such as calorie restriction or reducing the amount of food, lead to a shrinking of the nucleus.

"Calorie restriction does so many different things, and no one knows exactly how it extends life expectancy," says the scientist.

According to the scientists who conducted the study, keeping nuclei small can slow down aging. To test this idea, they developed an artificial way to anchor rDNA to the membrane surrounding the nucleus of yeast cells so that they could control when it is anchored and when it is not.

The researchers found that binding the nucleus was sufficient to keep it compact, and small nuclei slowed aging to about the same extent as calorie restriction.

Interestingly, the nuclei did not expand at the same rate throughout life as the cells aged. They remained small for most of the yeast's life, but when a threshold size was reached, the nuclei suddenly began to grow rapidly and expand to a much larger size. After reaching this threshold, the cells survived for an average of about five more cell divisions.

"When we saw that it was not a linear increase in size, we realized that something really important was happening. It turns out that exceeding the threshold serves as a mortality timer, counting down the last moments of a cell's life," explained Dr. Ignacio Gutierrez, lead author of the study.

During aging, DNA accumulates damage, some of which can be devastating to the cell. During the tests, the team found that large nuclei have less stable rDNA than smaller ones. In addition, when the structure is large, proteins and other factors that do not normally enter the nucleus no longer linger in it. It's as if the nucleus becomes leaky, allowing molecules that could harm the fragile rDNA to pass through.

"The whole point of condensins is to separate biological reactions to help them work efficiently, but now that you have other proteins coming into the nucleus, it leads to genomic instability, which causes the end of the lifespan," said Dr. Tyler. These proteins can cause catastrophic problems such as chromosomal rearrangements.

Next, the researchers plan to study the effect of the nucleus on the aging of human stem cells. Stem cells are special because they have the potential to replace other types of cells when they die. But over time, stem cells stop dividing, so the researchers hope to use the knowledge gained during this project to prolong their existence.

"I was thrilled that we were able to link the structure of the nucleus to the repair process in such a way that it can be preserved from yeast to humans," the scientist commented.

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