New research published in Nature Genetics suggests that DNA damage may be a major factor in the aging process. The study, conducted by researchers at Erasmus University Medical Center in the Netherlands, found that RNA polymerase II, an enzyme responsible for transcribing DNA into RNA, often stalls while transcribing DNA in older mice.
The researchers analyzed the livers of two-year-old mice and discovered that up to 40% of all RNA polymerase II complexes had stalled. This stalling not only interrupts the transcription process but also leads to disruptions in gene expression and cellular pathways. These pathways are essential for functions such as nutrient sensing, energy metabolism, immune function, and cellular damage repair, all of which are known to be affected by aging.
The study also revealed that larger genes are more prone to stalling, leading to a bias towards the expression of smaller genes. The researchers suspect that accumulated DNA damage is the cause of this stalling. When RNA polymerase II encounters damaged DNA, it becomes stuck, interfering with transcription and causing cellular pathways to malfunction.
To test their hypothesis, the researchers studied genetically altered mice that lacked the usual DNA repair machinery. These mice exhibited many features of premature aging and had significantly shortened lifespans. The rate of transcription was noticeably lower in these mice compared to healthy controls.
While the implications of this study are intriguing, there are currently no immediate therapeutic applications. However, understanding the mechanisms behind the aging process is crucial for developing effective interventions in the future. In the meantime, individuals can take steps to reduce DNA damage, such as avoiding behaviors like smoking and excessive UV light exposure. Additionally, planned caloric restriction may help alleviate transcriptional stress.
This research sheds light on the role of DNA damage in the aging process and provides valuable insights into the inner workings of cellular pathways. Further studies will be needed to fully understand the complex relationship between DNA damage, gene expression, and aging.