Despite centuries of medical research, pivotal questions about aging persist. A recent study by German scientists, published in Nature, suggests breakthrough insights into these questions.
Researchers from the University of Cologne and Max Plank Institute for Biology of Aging, revealed an age-related acceleration in gene transcription coupled with reduced precision and increased errors. They reported the following:
- Ageing is associated with a decline in physiological homeostasis, which is partly due to impaired cellular processes such as transcription and RNA splicing.
- The speed of RNA polymerase II (Pol II), the enzyme responsible for transcribing DNA into RNA, increases with age in all five metazoan species studied (nematodes, fruit flys, mice, rats, and humans).
- This increase in Pol II elongation speed is associated with 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 signaling, both reversed most of these ageing-related changes in transcription and splicing.
- 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.
The authors concluded that their findings uncover fundamental molecular mechanisms underlying animal ageing and lifespan-extending interventions, and point to possible preventive measures.
In particular, they suggest that slowing down the speed of RNA polymerase II could be a promising strategy for extending lifespan. This is because a slower Pol II would have more time to proofread transcripts, resulting in fewer errors. Additionally, a slower Pol II would be less likely to disrupt chromatin structure, which is important for gene regulation.
Image credits: kjpargeter on Freepik
Skin Ageing & Challenges 2023, this November, will elaborate on the latest discovered molecular mechanisms in aging.
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