A team of researchers at Nagoya University has found that aldehydes, a class of organic compounds, are metabolic byproducts associated with premature aging. The researchers, led by Yasuyoshi Oka, hypothesized that there might be a link between aldehydes and aging, as individuals with premature aging disorders, such as AMeD syndrome, exhibit inadequate activity of enzymes that break down aldehydes.
Aldehydes are highly reactive with DNA and proteins, forming DNA-protein crosslinks (DPCs) that block important enzymes in cell proliferation and maintenance processes. This malfunction can lead to premature aging. The researchers used a method called DPC-seq to investigate the link between aldehyde accumulation and DNA damage in premature-aging disease patients.
The study, published in Nature Cell Biology, found that the TCR complex, VCP/p97, and the proteasome are involved in the removal of formaldehyde-induced DPCs in actively transcribed regions. This suggests that the clearance of aldehydes is crucial in preventing premature aging. The researchers confirmed this by using a mouse model lacking both aldehyde clearance processes and the TCR pathway, which showed worse AMeD syndrome symptoms.
The researchers believe that their findings have implications that extend beyond genetic diseases, as aldehyde-induced DNA damage may play a role in the aging process in healthy individuals as well. By identifying aldehydes as a contributing factor to aging, this study sheds light on the intricate connection between environmental factors and cellular aging, which could have significant implications for human health and lifespan.
"Our research opens up new avenues for understanding the underlying mechanisms of premature aging diseases and offers potential targets for therapeutic intervention," said Professor Oka.
"By elucidating the role of aldehydes in DNA damage and aging, we are paving the way for future studies aimed at developing novel treatments and interventions."