Aging therapy

Hypertension drug extended the life of worms by a quarter

Svetlana Maslova, Hi-tech+

The first preclinical experiments have shown the effectiveness of an inexpensive drug in the treatment of aging. Presumably, a similar effect can be achieved in humans, the authors believe. Their main goal is active longevity, not a source of youth. In laboratory worms, the drug on average almost doubled the period of active old age and, in general, extended life by a quarter.

Experiments by Japanese scientists from Osaka City University have shown that the drug metolazone activates the mitochondrial stress response and thereby increases the lifespan of worms. Currently, metolazone is used to treat heart failure and hypertension. Now scientists are revealing new properties of the drug.

Article by Ito et al. Metolazone upregulates mitochondrial chaperones and extends lifespan in Caenorhabditis elegans published in the journal Biogerontology – VM.

Graph from the press release of Osaka City University Blood Pressure Drug may be Key to Increasing Lifespan, New Study Shows – WM.

Previous studies have shown that mitochondria play an important role in the aging process. For example, when mitochondria are damaged in any way, their function is disrupted, but recovery occurs with the help of the mitochondrial unfolded protein response (UPRmt). Currently, the hypothesis is being studied that it is possible to increase life expectancy by activating UPRmt.

Now scientists have managed to identify several compounds that activate UPRmt and increase the lifespan of C.elegans worms, which are often used as model organisms in the early stages of preclinical studies.

If the substance activated the hsp-6 gene (Hspa9 in humans), which is strongly expressed in UPRmt, then the body of the worms began to glow, indicating to scientists the effectiveness. As a result, out of 3,000 compounds, scientists were able to identify the most promising metolazone.

It is noteworthy that with certain mutations, metolazone did not increase the lifespan of worms. So scientists found out that the drug probably acts on the UPRmt pathway, since mutations in these genes were important for the function of the mitochondrial unfolded protein response.

When the scientists tested metolazone on human cells, the treatment triggered Hspa9 expression, also pointing to the UPRmt pathway. "This suggests that the effect of the drug associated with UPRmt extends to several types," the authors concluded.

While their research is at the earliest stage, however, given that metolazone has already been approved for human use, further conclusions can be obtained faster. The authors hope that in the future their approach will extend the active longevity of a person.

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