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A team of researchers from Nagoya University in Japan determined that aldehydes are metabolic waste linked to premature ageing.
Their findings, published in Nature Cell Biology, shed light on premature ageing illnesses as well as prospective techniques for combating ageing in healthy people, such as limiting exposure to aldehyde-inducing chemicals including alcohol, pollution, and tobacco. Aldehydes can have a negative impact on one's health. However, the group's findings indicate that these negative impacts also include ageing, which was discovered by Yasuyoshi Oka, Yuka Nakazawa, Mayuko Shimada, and Tomoo Ogi of Nagoya University. "DNA damage is linked with ageing phenotypes," said Oka. "However, for the first time, we propose a relationship between aldehyde-derived DNA damage and premature ageing." The researchers hypothesised that there might be a link between aldehydes and ageing since individuals with premature ageing disorders, like AMeD syndrome, exhibit inadequate activity of enzymes, like ALDH2, that break down aldehydes. For healthy individuals, ALDH2 is also important in our response to alcohol. When a person drinks wine or beer, the liver metabolises the alcohol into aldehydes so it can be eliminated from the body. The activity of ALDH2 is important for converting the aldehydes into a non-toxic substance. Aldehydes are harmful because they are highly reactive with DNA and proteins. In the body, they form DNA-protein crosslinks (DPCs) that block important enzymes in typical cell proliferation and maintenance processes, causing these processes to malfunction and the patient to age. Focusing on DPCs caused by aldehyde, the scientists used a method called DPC-seq to investigate the link between aldehyde accumulation and DNA damage in premature-ageing disease patients. In a series of experiments, the researchers discovered that the TCR complex, VCP/p97, and the proteasome are involved in the removal of formaldehyde-induced DPCs in actively transcribed regions. This was confirmed by a mouse model lacking both aldehyde clearance processes and the TCR pathway that showed worse AMeD syndrome symptoms. These processes are important because they are related to the clearance of aldehydes. It suggests an association between premature ageing diseases and aldehyde accumulation. Professor Ogi is hopeful about the implications of their findings, stating: "By elucidating the mechanism by which DNA damage heals quickly, we have revealed part of the cause of genetic premature ageing." "Our research opens up new avenues for understanding the underlying mechanisms of premature ageing diseases and offers potential targets for therapeutic intervention," Oka said. "By elucidating the role of aldehydes in DNA damage and ageing, we are paving the way for future studies aimed at developing novel treatments and interventions." He continued: "The development of therapeutic drugs has not progressed because we have not fully understood the causes of AMeD syndrome and Cockayne syndrome. This study suggests that the patient's pathological condition is related to DPC derived from aldehydes generated within cells. These results are expected to help in the search for compounds that remove aldehydes, thus aiding in the formulation of therapeutic drug candidates." (ANI)
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