A team of researchers from Nagoya University in Japan determined that aldehydes are metabolic waste associated with premature aging.
Their findings, published in Nature Cell Biology, shed light on diseases that cause premature aging as well as potential techniques to combat aging in healthy people, such as limiting exposure to aldehyde-inducing chemicals, including alcohol, pollution and tobacco. .
Aldehydes can have negative effects on one’s health. However, the group’s findings indicate that these negative effects also involve aging, which was discovered by Yasuyoshi Oka, Yuka Nakazawa, Mayuko Shimada and Tomoo Ogi of Nagoya University.
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“DNA damage is linked to the aging phenotype,” Oka said. “However, for the first time, we propose a connection between aldehyde-derived DNA damage and premature aging.”
Researchers speculate that there may be a connection between aldehydes and aging because individuals with premature aging disorders such as AMED syndrome exhibit insufficient activity of enzymes, such as ALDH2, which break down aldehydes.
For healthy individuals, ALDH2 is also important in our response to alcohol. When a person drinks wine or beer, the liver metabolizes the alcohol into aldehydes so that it can be excreted from the body. The activity of ALDH2 is important for converting aldehydes into non-toxic substances.
Aldehydes are harmful because they are highly reactive with DNA and proteins. In the body, they form DNA-protein crosslinks (DPCs) that block enzymes important in specific cell proliferation and maintenance processes, causing these processes to deteriorate and the patient to age.
Focusing on DPCs caused by aldehydes, scientists used a method called DPC-seq to investigate the relationship between aldehyde accumulation and DNA damage in patients with premature aging.
In a series of experiments, the researchers found that the TCR complex, VCP/p97, and the proteasome are involved in formaldehyde-induced DPC removal from actively transcribed regions. This was confirmed by a mouse model lacking both aldehyde clearance processes and the TCR pathway, which showed worse symptoms of AMED syndrome.
These processes are important because they relate to the extraction of aldehydes. This suggests a connection between premature aging diseases and aldehyde accumulation.
Professor Ogi is optimistic about the implications of their findings, saying: “By elucidating the mechanism by which DNA damage is quickly repaired, we have revealed part of the genetic cause of premature ageing.”
“Our research opens new avenues for understanding the mechanisms underlying premature aging diseases and provides potential targets for therapeutic intervention,” Oka said. “By elucidating the role of aldehydes in DNA damage and aging, we are paving the way for future studies aimed at developing new treatments and interventions.”
He added: “The development of therapeutic drugs has not progressed because we do not fully understand the causes of AMED syndrome and Cockayne syndrome. This study shows that the patient’s pathological condition is related to DPC derived from aldehydes generated within cells. These results are expected to help in the discovery of aldehyde-removing compounds, which will aid in the development of therapeutic drug candidates.
