Our cells are powered by tiny mitochondria, but with age, these cellular power plants become increasingly dysfunctional, in the quest for the anti-aging fountain of youth some scientists are investigating ways to repair these fundamental structures.
When mitochondria are damaged sometimes a process called mitochondria unfolding protein response becomes triggered and this mechanism involves the repairing of mitochondria, some anti-aging scientists believe that we could live longer and healthier if this process could be activated by taking medication.
“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 investigating whether there are any pre-existing drugs that can trigger UPRmt.
The scientists first screened around 3,000 known drugs in worms that were genetically engineered to glow when the hsp-6 gene was activated; this gene is known to be highly expressed during the process of UPRmt.
Metolazone quickly stood out as having significant potential in its effect on the hsp-6 gene; this drug is commonly used to treat high blood pressure being in clinical use for close to 50 years. The lifespan-extending effect of the drug was tested on C.elegans worms, this organism is frequently used in early preclinical anti-aging research.
Metolazone was confirmed to significantly extend the lifespan of the roundworms, and this anti-aging effect was not seen when the team blocked the activity of several genes known to play a role in UPRmt, affirming that the anti-aging effect potentiated by metolazone was most likely a result of activating that targeted specific mitochondrial repair process.
Then the effect of metolazone was looked at on the hsp-6 gene in human cell lines known as Hspa9. The drug heightened expression of the gene, adding weight to the team’s hypothesis that this drug-related UPRmt activation could translate into mammals.
Although this work is still in its early stages, it holds the promise of anti-aging potential for the future, offering valuable building blocks for the science of lifespan extension, particularly in the confirmation of a link between extended longevity and the activation of this mitochondrial repair process. This work also highlights the value in studying pre-existing and pre-approved medications, especially those 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.”
