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article imageBlood pressure drug may be key to increasing lifespan

By Tim Sandle     Dec 22, 2020 in Science
New research looking at mechanisms to increase life expectancy, or at least to reduce aging, has demonstrated how blood pressure drugs may have some beneficial effect. Data so far relates to an animal model.
For how long is is possible to live for? Can anti-aging medications also improve overall health and slowdown cognitive decline? These are two theoretical questions that different research groups have been grappling with. In terms of new research, it appears that certain medications may exert an effect upon mitochondria. The mitonchrodion are organelles found in large numbers in most cells, in which the biochemical processes of respiration and energy production occur. Some scientists are of the view that free radicals produced by mitochondrial activity damage cellular components, leading to aging. It is possible, in theory, for this process to be reversed and the new research has been exploring this.
The research comes from Osaka City University, Japan. Researchers have uncovered that an existing drug that can activate a mitochondrial stress response that prolongs lifespan in the worm Caenorhabditis elegans. The worm shares many similarities at the molecular level making it a good candidate for a model organism.
This was demonstrated using an anti-hypertension drug called Metolazone which is used to treat heart failure and high blood pressure. The study found that the administration of the drug prolongs C. elegans lifespan. The implication is that the drug has the potential for repurposing into anti-aging pharmaceutical drugs for humans.
The video below explains more about the research methodology:
For the study, the researchers screened some 3,000 different drugs, using worms as the model. The worms had been genetically engineered to glow if one of the candidate medications activated a gene called hsp-6. This gene is highly expressed when a process termed mitochondrial unfolded protein response (UPRmt) occurs. The UPRmt process repairs mitochondria and this aids cell survival. It is reasoned that it is possible to increase lifespan by selecting medications that can activate UPRmt.
Of the 3000 meeications selected, it was noted that 1300 were off-patent drugs that had been approved by the U.S. Food and Drug Administration. The other 1700 drugs were candidate bioactive drugs that have yet to be approved. The optimal drug was an existing blood pressure medication (Metolazone), and this discovery stems the way for further trials.
The research has been published in the journal Biogerontology. The research paper is titled "Metolazone upregulates mitochondrial chaperones and extends lifespan in Caenorhabditis elegans."
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