Gene transcription may be responsible for aging, study finds

Jun 12, 2023

PeopleImages/iStock

By subscribing, you agree to our Terms of Use and Policies You may unsubscribe at any time.

University of Cologne researchers in Germany have figured out how to slow down aging by potentially controlling gene transcription. This process, they argue, becomes faster and more error-prone as we age and slowing it down and fixing it may be key to thwarting time.

This is according to a report by Euronews Next published on Saturday.

Dr Andreas Beyer, the lead researcher, told the news outlet this is a “major discovery.”

He further explained how "each cell is different, and what makes them different are the different genes that are activated in it. This activation is called transcription". This process must be error-free in order to ensure that genes function properly.

"You need to create the right amount of transcripts for each gene and have an exact copy of the gene sequence, but also, you need to activate the exact genes that the cell needs to function as it should," Beyer told Euronews Next.

He noted that the "machine" responsible for these tasks is called Pol II (RNA polymerase II) and as we age it makes more and more mistakes.

“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,” Beyer said.

The discovery is groundbreaking as it means that fixing gene transcription can result in reversing aging. “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," Beyer told Euronews Next.

This is not the first anti-aging study to toy with genes.

In January of 2023, scientists at Boston Labs found that human bodies have a backup copy of their youth that can be genetically triggered to regenerate the cells in the body. They came to this conclusion after successfully reversing aging in mice.

The experiment saw the animals regain their eyesight when scientists injected a cocktail of human skin cells into the eyes of blind mice. Scientists even successfully restored mice's brains, muscle tissue, and kidneys to much younger levels. The researchers therefore argued that a loss of information and loss in the ability of cells to read their original DNA is what made them age and malfunction and fixing this process could result in a return to youth.

In an older study published in May of 2020, MIT neuroscientists discovered an enzyme called HDAC1 that had the potential to reverse age-related DNA damage to cognitive and memory-linked genes.

"It seems that HDAC1 is really an anti-aging molecule," said at the time the Director of MIT's Picower Institute for Learning and Memory Li-Huaei Tsai, who was also senior author of the study, in a Science Daily report. "I think this is a very broadly applicable basic biology finding, because nearly all of the human neurodegenerative diseases only happen during aging."

Injecting a drug that triggered regeneration of the enzyme in mice was found to reverse cognitive decline associated with old age.

Increasingly, it seems that genetically toying with DNA may be the solution to thwarting and even reversing aging. But can we really fight nature or are any advancements made only temporary breakthroughs?

The findings of the new study are published in Nature.

Study abstract:

Physiological homeostasis becomes compromised during ageing, as a result of impairment of cellular processes, including transcription and RNA splicing. However, the molecular mechanisms leading to the loss of transcriptional fidelity are so far elusive, as are ways of preventing it. Here we profiled and analysed genome-wide, ageing-related changes in transcriptional processes across different organisms: nematodes, fruitflies, mice, rats and humans. The average transcriptional elongation speed (RNA polymerase II speed) increased with age in all five species. Along with these changes in elongation speed, we observed changes in splicing, including a reduction of unspliced transcripts and the formation of more circular RNAs. Two lifespan-extending interventions, dietary restriction and lowered insulin–IGF signalling, both reversed most of these ageing-related changes. Genetic variants in RNA polymerase II that reduced its speed in worms and flies increased their lifespan. Similarly, reducing the speed of RNA polymerase II by overexpressing histone components, to counter age-associated changes in nucleosome positioning, also extended lifespan in flies and the division potential of human cells. Our findings uncover fundamental molecular mechanisms underlying animal ageing and lifespan-extending interventions, and point to possible preventive measures.