Can Blood Pressure Medication Prevent Aging?

Blood pressure medication metolazone activates mitochondrial unfolded protein response (UPRmt) process that repairs mitochondria, and promotes cell survival.

People have always been fascinated with immortality. Even though modern medicine does not strive to find the fountain of youth, research into the mechanisms of aging and the possibility of anti-aging drugs is promoted.

It is known that mitochondria play an important role in aging.

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‘Blood pressure medication metolazone activates mitochondrial unfolded protein response (UPRmt) process that repairs mitochondria, and promotes cell survival. The genes atfs-1, nkcc-1, and ubl-5 are essential for metolazone function.’
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Specifically when damage to mitochondria occurs their function is impaired. To repair the mitochondria and promote cell survival, a process called mitochondrial unfolded protein response (UPRmt) occurs. By identifying the drugs that activate UPRmt, some scientists think it is possible to increase the lifespan of mitochondria.

The study conducted by Dr. Eriko Kage-Nakadai and her colleagues from Osaka City University in Japan is published in the journal Biogerontology.

Dr. Kage-Nakadai has explained that though aging is not a disease, drugs can slow down aging and reduce or prevent their negative effects on a patient’s health. Current research has shown promising results.

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Experiments were conducted by using a commonly used biological research model - Caenorhabditis elegans worm. Several compounds were identified that can increase the lifespan of worm by activating UPRmt.

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When UPRmt is activated, hsp-6 gene is highly expressed. About 3,000 drugs were screened in worms that were engineered to glow if drug treatment activates hsp-6. Out of the 3,000 drugs, 1300 were off-patent drugs approved by the USFDA, EMA, and other agencies, and the remaining 1700 were unapproved bioactive ones.

By using this method, the researchers identified the drug metolazone, which increased the lifespan of the worm. Metolazone is a thiazide-like diuretic which used to treat high blood pressure and heart failure.

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In worms having mutations in the gene atfs-1, nkcc-1, and ubl-5 metolazone did not extend the lifespan of the worms. The genes atfs-1 and ubl-5 are essential for UPRmt function. This suggests that metolazone acts on the UPRmt pathway. The third gene nkcc-1 codes for a protein that is targeted by metolazone for its anti-hypertensive effect.

Metolazone also activated the expression of hsp-6 (Hspa9 in humans) in HeLa cells (a human cell line commonly used in biological research). This shows that the drug’s UPRmt-related effects can be seen in multiple species.

Talking about the broader significance of her work, Dr. Kage-Nakadai comments, "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. Worms always give us many hints."

The researchers have stated that this work is just the start and it can provide new anti-aging drugs. In future humans living longer than 120 years can become a reality.

Source-Medindia