A team of researchers from Nagoya University in Japan discovered that aldehydes are metabolic waste that contributes to premature ageing.
Their research, which was published in Nature Cell Biology, provides knowledge on premature ageing diseases as well as potential techniques for preventing ageing in healthy people, such as limiting exposure to aldehyde-inducing chemicals including alcohol, pollution and cigarettes.
Aldehydes may be harmful to a person’s health. However, according to the group’s results, ageing is also one of these negative effects, as Yasuyoshi Oka, Yuka Nakazawa, Mayuko Shimada, and Tomoo Ogi of Nagoya University have found.
Oka stated, “DNA damage is linked with ageing phenotypes. However, for the first time, we propose a relationship between aldehyde-derived DNA damage and premature ageing.”
The researchers speculated that there may be a link between aldehydes and ageing since people with premature ageing illnesses, such as AMeD syndrome, had low activity of enzymes that break down aldehydes, such as ALDH2.
Aldehydes are harmful since they react strongly with DNA and proteins. In the body, they generate DNA-protein crosslinks (DPCs) that prevent essential enzymes from participating in normal cell proliferation and maintenance processes, causing these processes to fail and the patient to age.
After a series of tests, the researchers revealed that the TCR complex, VCP/p97, and the proteasome play roles in the removal of formaldehyde-induced DPCs in actively transcribed areas. A mouse model lacking both the aldehyde clearance processes and the TCR pathway showed worse AMeD syndrome symptoms, which confirmed this result.
Professor Ogi is optimistic about the implications of their findings, saying, “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.”