What are jumping genes and how they affect aging – 11/03/2023 – Science

Almost a hundred years ago, American scientist Barbara McClintock revolutionized the way we understand genes and DNA.

Chromosomes, she deduced from studying corn, were not fixed, stable chains of information, but contained pieces of DNA that bounced from one side to the other.

These “jumping genes” or transposable elements, also known as transposons, are essential for understanding, for example, complex diseases such as cancer or certain degenerative neurological diseases.

Although they were first described in the late 1920s by McClintock, the scientific community only discovered — or became interested in knowing — their importance decades later, and the cytogeneticist finally received the Nobel Prize for Medicine in 1983.

Now, a new study by scientists at Eötvös Loránd University (ELTE) in Hungary has revealed how these “jumping genes” affect aging, as well as possible methods to slow or mitigate them.

When these transposons move a lot — and this happens more in adult life — they destabilize the genetic code, and this could be one of the reasons for aging, the researchers conclude.

What are ‘jumping genes’

Transposons are pieces of DNA that have the ability to be removed from one area of ​​the genome and go to a new location. These elements can make a copy of themselves to move to other areas of the DNA.

“They can pass from one fragment of DNA to another, which essentially also means that they can alter the functioning of other genes if they are inserted in an unfortunate position,” explains Nazif Alic to BBC News Mundo (BBC service in Spanish). , who is professor of genetics, evolution and the environment at University College London (UCL).

Animal genomes typically have multiple copies of these elements.

“Some of them no longer have the ability to jump. They are, in some ways, flawed. But those that can do that can jump and get into any gene, so essentially they can change any gene,” adds Alic.

These changes are generally harmful.

In multicellular organisms there are two main types of cells. On the one hand, there are the germ lines, also known as the germ line, which are the reproductive ones, those that will give rise to sperm and eggs and, therefore, will be responsible for passing the genetic material to the children.

And on the other hand, there are somatic cells, which are those that constitute the growth of tissues and organs in multicellular living beings.

Exceptionally, however, some may move when reproductive cells are formed, integrating within some genes and altering their expression, known as a “de novo mutation.”

This causes “some diseases, such as certain cases of hemophilia or leukemia, colon or breast cancer, and certain degenerative neurological diseases caused by their integration into key genes of adult somatic cells,” wrote biologist Manuel Peinado Lorca on the website The Conversation . Lorca is professor emeritus at the University of Alcalá de Henares, in Spain.

The relationship with aging

Researchers Ádám Sturm and Tibor Vellai, from Eötvös Loránd University in Hungary, were able to establish a link between these transposons or “jumping genes” and aging. The study was published by the journal Nature Communications.

Scientists have identified a specific process, called the Piwi-piRNA pathway, that helps control or otherwise silence transposons.

This process works in certain types of cells that do not age, such as cancer stem cells, as well as in an enigmatic and fascinating animal known as the immortal jellyfish (Turritopsis dohrnii).

In the study, researchers from the Hungarian university carried out experiments with Caenorhabditis elegansa type of worm approximately 1 mm long that is commonly used in experiments on aging, studies of age-related diseases, and mechanisms of longevity.

By increasing the Piwi-piRNA pathway in the worm, it lived significantly longer.

Sturm and Vellai had already theorized in two previous studies published in 2015 and 2017 about the relationship between this mechanism and the concept of biological immortality. Now they have managed to test it experimentally.

Researchers have used several techniques to silence the activity of jumping genes.

When they did this with specific transposons in the worms, the animals showed signs of slower aging. And even more: when they controlled several transposons at the same time, the effects of this extension of lifespan increased.

The experiment shows a significant advantage in extending lifespan, explained Ádám Surm, one of the study’s authors, and “this opens the door to countless potential applications in the world of medicine and biology.”

Additionally, the study found epigenetic changes (genetic modifications that affect genetic activity without altering the DNA sequence) in the worms’ DNA as they aged, specifically in transposons, or jumping genes.

Analyzing these changes, according to Tibo Vellai, could be a method “to determine age from DNA, providing an accurate biological clock.”

So, by better understanding “jumping genes” and the pathways that control them, scientists may be able to find new ways to extend life and improve health in later years.

“In the field of aging, we have known for some time that transposons appear to be activated when animals age, but until now there have been few studies that have tried to see if this is directly related to aging,” explains Nazif to BBC News Mundo.

However, just because something happens more with age doesn’t mean it’s what actually causes aging. It could simply be a result of aging itself, Alic argues.

To differentiate between causality and simple correlation, researchers do experiments in which they prevent something from happening, to see if this actually extends the lifespan of a specific model organism.

Other studies had already tried to deactivate jumping genes, “but they didn’t necessarily do it as specifically and perhaps as conclusively as this study did”, explains the UCL researcher.

Science is also studying other ways to stop the wear and tear that occurs with advancing age.

In addition to promoting physical exercise and healthy eating, which help to minimize the problems of advancing age, there are pharmaceutical companies that are looking for formulas to kill senescent (aged) cells, and laboratories that are betting on cellular rejuvenation through transcriptional reprogramming of cells.

“As far as I know, none of this work has reached the clinic yet, so I think it’s still an area with a lot of potential,” concludes Alic.