Scientists from the University of Cologne in Germany have uncovered some intriguing findings that could slow down the aging process. They have learned that, as we get older, a critical process in our cells, called gene transcription, speeds up. This process involves making a copy of a specific DNA strand in the form of RNA.

However, this copying becomes not only quicker but also less accurate and more prone to errors. A fresh investigation led by a group of German scientists and published in the respected journal Nature might have finally unlocked the solutions we’ve been seeking.

Dr. Andreas Beyer, the lead researcher said, “This is, so far, the only eureka moment in my life. I mean, this is a type of discovery that you don’t make every other day.” He further said that “there’s a storm on Twitter. Some colleagues are very excited.”

Past research

A decade ago, when Beyer and his research group embarked on their investigative mission, the standard approach to studying aging was quite limited, says Beyer.

He points out that earlier investigations mainly focused on understanding which genes become active or inactive as you age and how this impacts the cell’s regulation and metabolism.

However, what hadn’t been explored was how the actual process of transcription alters during the aging process. This avenue of exploration holds the potential to provide valuable insight that could eventually assist us in tackling or preventing decline.

The process of transcription

Beyer’s research revolves around transcription, a crucial process whereby a cell crafts an RNA copy of a DNA segment. This copied material carries vital genetic instructions necessary for producing fresh proteins within cells. These proteins dictate the well-being and operation of cells, which, in turn, constitute all living entities.

As our lives unfold, our cells renew themselves. However, each cell remains distinct, and the dissimilar genes activated within them account for this diversity, as clarified by Beyer. This activation process is referred to as transcription.

The accuracy of transcription is pivotal because genes assign distinct roles to cells. Each gene’s transcripts need to be produced accurately, both in quantity and the exact sequence. Moreover, only necessary genes must be switched on for the cell to perform its intended function.

Generation of transcription copies

Diverse cell types populate the human body—nerve cells, muscle cells, blood cells, skin cells, and others. Given that each cell type serves a distinct purpose, a different ensemble of genes is activated (transcribed) in each.

Beyer terms the “machinery” responsible for generating these transcription copies of gene sequences as Pol II (RNA polymerase II). The research team’s breakthrough lies in the observation that transcription speeds up with age.

This swifter pace prompts Pol II to introduce more errors, yielding essentially “flawed” copies that can contribute to various ailments.

Beyer elaborated, “If Pol II gets too fast, it makes more mistakes, and then the sequence is not identical anymore to the genome sequence. The consequences are similar to what you have when there are mutations in the genome itself.”

Putting a stop to flawed cell copies

Previous scientific studies have already demonstrated that adopting low-calorie diets and interfering with insulin signaling—obstructing the communication between insulin and cells—could effectively slow down the aging process and extend lifespan in a variety of animals.

In their series of experiments, Beyer’s team embarked on an exploration to uncover whether these strategies could influence the speed of Pol II and decrease the production of flawed genetic copies.

This research initiative, involving the collaborative effort of twenty-six individuals across six distinct laboratories, initially concentrated on worms, mice, and fruit flies that were genetically engineered to impede insulin signaling.

Additionally, mice following a low-calorie diet were assessed to gauge the impact on cell transcription during the aging process. In both scenarios, Pol II’s pace was observed to be more measured, resulting in fewer errors.

Reverse #Ageing by Studying its Effects on Transcription
"It opens up a really fundamental new area of understanding how and why we age."
— Dr. Lindsay Wu, UNSW Sydney @LindsayWu_UNSW @UNSW
Pol II could be targeted for #drug research to slow down the ageing process.@Nature https://t.co/s935pX15ll pic.twitter.com/4dkmD9mFH4

— World Laureates Forum (@wlaforum) May 4, 2023

Beyer and his associates scrutinized the lifespan of fruit flies and worms that bore the genetic alteration leading to Pol II’s deceleration. Astonishingly, these creatures lived ten to twenty percent longer than their counterparts without the mutation.

Further reinforcing their findings, when the research team employed gene editing to reverse these genetic alterations in worms, the creatures’ lifespans experienced a reduction, thereby substantiating a direct cause-and-effect connection.

In a bid to validate their experiment’s applicability to humans, they conducted assessments using blood samples from both young and elderly individuals.

Argyris Papantonis, one of the principal investigators, remarked, “And when we compared the young cells to the very old cells, in vitro, we got exactly the same results.”

Universal phenomenon of transcription

The outcomes spanning multiple species confirm a fundamental truth. This phenomenon is not confined to a particular species but rather applies universally to the process of aging, as Beyer highlighted.

He stated, “Our study is saying that, for instance, having a healthy diet or, this caloric restriction intervention, would improve the quality of the transcription of the RNA production in the cell. And this would then have beneficial effects for the cells in the long run.”

The significance of these findings extends to potential cancer prevention, according to Papantonis. He points out that cancer tends to emerge later in life due to accumulating errors. By curbing these errors, it might be feasible to curb the development of cancer or other late-life diseases.

Furthermore, these revelations hold the promise of advancing our comprehension of the aging process itself. As Beyer puts it, this may allow us to “better understand interventions, which I think opens up new opportunities for delaying aging or expanding healthy aging.”