Biology

Common blood pressure drug found to have lifespan-extending potential

Common blood pressure drug fou...
Preclinical research suggests a drug used to treat hypertension may offer lifespan-extending effects by helping activate a mitochondrial repair process
Preclinical research suggests a drug used to treat hypertension may offer lifespan-extending effects by helping activate a mitochondrial repair process
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Preclinical research suggests a drug used to treat hypertension may offer lifespan-extending effects by helping activate a mitochondrial repair process
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Preclinical research suggests a drug used to treat hypertension may offer lifespan-extending effects by helping activate a mitochondrial repair process

Scientists from Osaka City University have found metolazone, an anti-hypertension drug that has been around for almost 50 years, can kickstart a lifespan-extending cellular repair process in roundworms. The research suggests this mechanism could be translatable to humans, offering new research pathways in the search for an anti-aging drug.

Mitochondria are tiny structures that act like cellular power plants. As we age mitochondria become increasingly dysfunctional and, in the search for lifespan-extending medicines, some scientists are looking at ways to repair these fundamental structures.

When mitochondria are damaged a process called mitochondrial unfolded protein response (UPRmt) is sometimes triggered. This mechanism involves the repair of mitochondria, and some anti-aging researchers suspect we could live longer if this process could be activated by taking a drug.

“Even though aging is not a disease, drugs may slow down aging and mitigate or prevent its negative effects on our health,” says Eriko Kage-Nakadai, one of the scientists working on the new research.

Kage-Nakadai led a team of scientists from Osaka City University to set out to discover whether there are any pre-existing drugs that can trigger UPRmt. The first step involved screening around 3,000 known drugs in worms that had been genetically engineered to glow when a gene called hsp-6 is activated. This gene is known to be highly expressed during the process of UPRmt.

One drug called metolazone quickly stood out as significant in its effect on the hsp-6 gene. Metolazone is a common drug used to treat high blood pressure and it has been in clinical use for nearly 50 years.

The lifespan-extending effect of metolazone was then tested on C. elegans worms, an organism frequently used in early preclinical anti-aging research. Metolazone was confirmed to indeed significantly extend the lifespan of the roundworms.

The lifespan-extending effect of metolazone was not seen when the researchers blocked the activity of several genes known to play a role in UPRmt. This affirmed that the anti-aging effects potentiated by metolazone were most likely a result of activating that specific mitochondrial repair process.

Finally, the researchers looked at the effect of metolazone on the hsp-6 gene (known as Hspa9 in humans) in human cell lines. The common blood pressure drug did heighten expression of the gene, adding weight to the hypothesis this drug-related UPRmt activation could translate into mammals.

It is still early days for this research, so don’t expect metolazone to suddenly be touted as an anti-aging miracle drug. But this new study offers valuable building blocks for the science of lifespan extension, particularly in its confirmation of a link between longevity and the activation of this mitochondrial repair process. Kage-Nakadai also points out the value in studying pre-existing and pre-approved drugs, especially ones that are off-patent, easily accessible, and known to be safe.

“What is particularly exciting is that we tested already available approved drugs here, and we have revealed the potential of repurposing existing drugs for aging control,” says Kage-Nakadai. “Worms always give us many hints.”

The new study was published in the journal Biogerontology.

Source: Osaka City University

7 comments
7 comments
usugo
being a drug used for 50 years, it should be relatively easy to compare the lifespan of longtime users of the drug as compared to the general population, to see if there is any significant life extension. I am predicting a: not really. If there was any clear cut effect it would have likely been already spotted.
michael_dowling
usugo: And how would you know if John Doe would have died earlier without the drug? Humans are a bit more complex than C. elegans worms.
paul314
In particular, if the drug is used to treat high blood pressure, who would be your control group? High blood pressure is already known to increase morbidity and mortality, so not people who were simply untreated. Maybe people whose high blood pressure was treated by other drugs? Maybe people who didn't have high blood pressure as they got older?
tony
Some people have mitochondria dysfunction maybe try it on them see if it helps.
Username
michael_dowling , paul314, They seem to be checking for a specific marker so a quick blood test of current users would give them an answer.
Brian M
@usugo
The drug was being given to patients with high blood pressure - So other life shortening conditions might be in play - So probably not a good basis for the evaluation of its efficacy on UPRmt/aging, although could to determine any unwanted side effects.
toni24
michael_dowling There must be a number of cases where twins have taken the drug, one getting it and the other not getting it. That would provide controls to base research on