The mitochondrial stress response is a part of our cells that produce energy to enhance the body’s functions, which is essential for extending life. Scientists from Osaka City University in Japan searched the chemical “library” of existing drugs and found that an antihypertensive drug called metolazone can prolong the life of Caenorhabditis elegans, marking the first development of anti-aging drugs step.
Scientists from Osaka City University in Japan searched the chemical “library” of existing drugs and found that an antihypertensive drug called metolazone can prolong the life of Caenorhabditis elegans, marking the first development of anti-aging drugs.
Since ancient times, people have been fascinated by ways to prevent aging, and extending life span has always been a deep desire of all mankind. People’s strong interest in promoting longevity has prompted people to study the mechanism of aging and the possibility of anti-aging drugs. So far, researchers have known that mitochondria play an important role in aging. Specifically, when mitochondria are damaged to some extent or their function is impaired, the mitochondrial unfolded protein response (UPR mt) repairs mitochondria and helps cells survive. Therefore, some scientists believe that by identifying drugs that activate UPR mt, life can be extended.
Dr. Eriko Kage-Nakadai of Osaka City University in Japan and her team are one of many research teams fascinated by the research on aging. As Dr. Kage-Nakadai explained, even if aging is not a disease, drugs can slow down aging and reduce or prevent its negative effects on our health. Researchers have discovered several compounds through experiments with Caenorhabditis elegans (a type of worm commonly used as a model in biological research) that trigger UPR mt to extend the life of the worm.
In the context of these previous studies, the research team screened approximately 3,000 drugs in the worm that were engineered to emit light when the drug treatment activates hsp-6, which is highly expressed when UPR mt occurs. Interestingly, among these 3,000 drugs, 1,300 are generic drugs approved by the FDA, EMA, and other agencies, and the remaining 1,700 are unapproved bioactive drugs.
In this way, Dr. Kage-Nakadai’s research team identified metolazone, a drug used to treat heart failure and high blood pressure. Then, they tested the drug on Caenorhabditis elegans and found that the drug can extend the life of wild-type worms. In addition, they found that in worms in which the atfs-1, ubl-5, and nkcc-1 genes were mutated (invalid), metolazone did not extend its lifespan. The first two genes are known to be essential for UPR mt function, which indicates that the inactivation loop is acting on the UPR mt pathway.
The third gene, nkcc-1, “encodes” a protein that is part of a family of proteins targeted by Metoprazone, which usually has antihypertensive functions. The fact that inactivating meprazole does not extend the lifespan of nkcc-1 mutant C. elegans suggests that the drug may need to block the nkcc-1 protein to activate the UPR mt pathway. In addition, metolazone induced the expression of hsp-6 (Hspa9 in humans) in HeLa cells (a human cell line commonly used in biological research), indicating that the drug’s UPR mt-related effects may span multiple species.
All in all, it is exciting that the researchers tested the approved drugs and revealed the potential of using existing drugs for aging control. This work is only the beginning, but it opens up a new path for the future of anti-aging drugs. Perhaps the limit of human life span will be longer than expected.
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