Despite centuries of research and advances in medicine, many mysteries remain unsolved, chief among them understanding what causes aging and how to slow or reverse it.
But a new study published in the scientific journal Nature may finally have the answers to these questions.
Researchers from the University of Cologne in Germany have not only found that gene transcription – the process by which a cell makes an RNA copy of a DNA strand – becomes faster with age, but less precise. and more prone to errors; they also discovered that certain processes could help us reverse this decline.
“It’s, so far, the only eureka moment of my life. I mean, it’s a type of discovery that you don’t make every other day,” said lead researcher Dr Andreas Beyer. , calling the results “Major Discovery”.
“There is a storm on Twitter. Some colleagues are very excited,” he told Euronews Next.
Before Beyer and his team launched their investigative project 10 years ago, the typical study of aging “simply looked at differential gene expression,” says Beyer.
Previous studies, he explains, asked questions such as “As you age, which genes are turned on and which genes are turned off?” and “How does this change regulation or metabolism in the cell?”
But no one wondered how the transcription process itself changes with age, a line of research that could yield insights to ultimately help us reverse or halt the decline.
Transcription, the key to healthy aging
Transcription is fundamental to Beyer’s research because it is the process by which a cell makes an RNA copy of a piece of DNA.
This copy is important because it contains the genetic information needed to make new proteins in a cell. Proteins determine the health and function of cells, and cells then structure all living things.
Throughout our lives, our cells regenerate, “but every cell is different, and what makes them different are the different genes that are activated in them,” says Beyer. “This activation is called transcription.”
Because genes give cells their raison d’être, their transcription must be perfect.
“You have to create the right amount of transcripts for each gene and have an exact copy of the gene sequence, but also, you have to turn on the exact genes that the cell needs to function as it should,” Beyer said.
There are many types of cells in the human body: nerve cells, muscle cells, blood cells, skin cells, etc. And because each cell performs a different function, a different set of genes are activated (transcribed) in each type of cell.
The “machine” – as Beyer calls it – responsible for making the transcriptional copy of gene sequences is called Pol II (RNA polymerase II).
And what his team discovered is that the transcription process speeds up as we age, and this accelerated transcription causes Pol II to make more errors, essentially leading to “bad” copies that can lead to many diseases.
“If Pol II goes too fast, it makes more errors, and the sequence is no longer identical to the genome sequence. The consequences are similar to what you have when there are mutations in the genome itself,” Beyer said.
Stop bad copies of cells, the second big breakthrough
Previous research had already proven that low-calorie diets and inhibiting insulin signaling – blocking the signal between insulin and cells – can delay aging and extend lifespan in many animals.
In their experiments, Beyer’s team investigated whether these had any impact in slowing down the speed of Pol II and reducing the number of defective copies.
The investigation – a joint collaboration of 26 people in six different labs – first worked with worms, mice and fruit flies genetically engineered to inhibit insulin signaling as well as dieting mice. low-calorie to determine cell transcription performance in old age. In both cases, Pol II reacted and traveled more slowly, making fewer errors.
Beyer and his team then tracked the survival of fruit flies and worms carrying the mutation that slowed Pol II, and the animals lived 10-20% longer than their non-mutant counterparts.
When the researchers used gene editing to reverse the worms’ mutations, the animals’ lifespans were shortened, establishing a causal link.
To test their experience in humans, they worked with blood samples from young and old individuals.
“And when we compared young cells to very old cells, in vitro, we got exactly the same results,” Argyris Papantonis, one of the lead researchers, told Euronews Next.
The cross-species results confirm that this is “really a general phenomenon that applies to aging, and not just specific to the single model of, say, flies,” Beyer said.
“Our study indicates that, for example, having a healthy diet or, this calorie restriction intervention, would improve the quality of transcription of RNA production in the cell. And this would then have beneficial effects for the cells in the long term. “.
The results could help prevent cancer from manifesting, Papantonis notes, because “it’s an end-of-life disease because of mistakes. Constraining mistakes could be a way to limit the emergence of cancer or end-of-life illness.
They may also allow us to “better understand aging, better understand what happens when we age” and ultimately “better understand interventions, which I believe open up new opportunities to delay aging or extend healthy aging,” Beyer said.