Despite centuries of medical research and development, many mysteries still remain unsolved, chief among them understanding what causes aging and how we can slow or reverse it.
But a new study published in the scientific journal Nature may have finally found the answers to these questions.
Researchers from the University of Cologne in Germany not only discovered that gene transcription – the process by which a cell makes an RNA copy of a DNA strand – becomes faster with age but less accurate and it’s easier to make mistakes; they also found that certain processes can help us reverse this rejection.
“This is, so far, the only eureka moment in my life. I mean, it’s the kind of discovery you don’t make every other day,” said Dr Andreas Beyer, the lead researcher, who called the findings “a major discovery”.
“There is a storm on Twitter. Some colleagues are very excited,” he told Euronews Next.
Before Beyer and his team began their investigation project 10 years ago, the standard study of aging “only looked at variation in gene expression,” Beyer said.
Previous studies, he explains, have asked questions like “When you get older, which genes are turned on and which genes are turned off?” and “How does it change the regulation or the metabolism in the cell?'”
But no one is asking how the transcription process itself changes as we age, a line of inquiry that could yield insights to ultimately help us reverse, or stop, denial.
Transcription, the key to healthy aging
Transcription is important 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 carries the genetic information needed to make new proteins in a cell. Proteins determine the health and function of cells, and cells then make up all living things.
Throughout our lives, our cells regenerate, “but every cell is different, and what makes them different is the different genes that are activated in it,” Beyer explains. “This activation is called transcription”.
Because genes give cells their purpose, their transcription must be flawless.
“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 activate the exact genes that the cell needs to function as it should,” says by Beyer.
There are many different types of cells in the human body: nerve cells, muscle cells, blood cells, skin cells, and so on. And because each cell performs a different function, a different set of genes is activated (transcribed) in each cell type.
The “machine” – as Beyer calls it – responsible for making transcriptional copies of gene sequences is called Pol II (RNA polymerase II).
And what his team discovered is that the process of transcription becomes faster as we age, and this accelerated transcription causes Pol II to go wrong, leading to essentially “bad” copies that can lead to many pain
“If Pol II goes too fast, it makes more mistakes, and then the sequence is no longer identical to the genome sequence. The consequences are similar to what you have when there are mutations in genome itself,” Beyer said.
Stopping bad cell copies, the second great achievement
Previous research has shown 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 sought to determine whether they had the effect of slowing down Pol II and reducing the number of false copies.
The investigation – a joint collaboration of 26 people in six different labs – first worked on worms, mice and fruit flies genetically modified to inhibit insulin signaling as well as on mice on a low-calorie diet to determine the performance of cell transcription in old age. In both cases, Pol II responded and traveled more slowly, making fewer mistakes.
Beyer and his team then monitored the survival of fruit flies and worms that carried a mutation that slowed Pol II, and the animals lived 10 percent to 20 percent longer than their non-mutant counterparts. .
When researchers used gene editing to reverse mutations in worms, the animals’ lifespans were shortened, establishing a causal connection.
To test their experiment on humans, they worked with blood samples from young and elderly individuals.
“And when we compared young cells with very old cells, in vitro, we got exactly the same results,” Argyris Papantonis, one of the principal investigators, told Euronews Next.
The cross-species results confirm that this is “really a general phenomenon that applies to aging, and not just specific to a model of, say, flies,” Beyer said.
“Our study says that, for example, having a healthy diet or, this caloric restriction intervention, will improve the quality of transcription of RNA production in the cell. And this will have beneficial effect for the cells in the long run.”.
The findings can help prevent the manifestation of cancer, said Papantonis, as “it is a late-life disease due to errors. Constraining errors may be a way of preventing the occurrence of cancer or late-life disease”.
They can also allow us to “better understand aging, better understand what happens when we age,” and ultimately, “better understand interventions, which I think opens up of new opportunities for delaying aging or extending healthy aging,” Beyer said.