Mifepristone Slows Aging in Flies

Researchers here note that mifepristone, an abortifacient drug, slows aging in flies. This is interesting, but the mechanisms of action so far have the look of being quite specific to circumstance and gender - it blocks a detrimental effect of mating in female flies that increases inflammation. So I'd wager that this will turn out to be of academic interest only at the end of the day. If reductions in inflammation are the primary downstream benefit, this class of drug probably compares poorly to senolytics in any case.

Studying one of the most common laboratory models used in genetic research - the fruit fly Drosophila - researchers found that the drug mifepristone extends the lives of female flies that have mated. Mifepristone, also known as RU-486, is used by clinicians to end early pregnancies as well as to treat cancer and Cushing disease. During mating, female fruit flies receive a molecule called sex peptide from the male. Previous research has shown that sex peptide causes inflammation and reduces the health and lifespan of female flies. Researchers found that feeding mifepristone to the fruit flies that have mated blocks the effects of sex peptide, reducing inflammation and keeping the female flies healthier, leading to longer lifespans than their counterparts who did not receive the drug.

The drug's effects in Drosophila appear similar to those seen in women who take it. "In the fly, mifepristone decreases reproduction, alters innate immune response and increases life span. In the human, we know that mifepristone decreases reproduction and alters innate immune response, so might it also increase life span?" Seeking a better understanding of how mifepristone works to increase lifespan, researchers looked at the genes, molecules, and metabolic processes that changed when flies consumed the drug. They found that a molecule called juvenile hormone plays a central role.

Juvenile hormone regulates the development of fruit flies throughout their life, from egg to larvae to adult. Sex peptide appears to escalate the effects of juvenile hormone, shifting the mated flies' metabolism from healthier processes to metabolic pathways that require more energy to maintain. Further, the metabolic shift promotes harmful inflammation, and it appears to make the flies more sensitive to toxic molecules produced by bacteria in their microbiome. Mifepristone changes all of that. When the mated flies ate the drug, their metabolism stuck with the healthier pathways, and they lived longer than their mated sisters who did not get mifepristone. Notably, these metabolic pathways are conserved in humans, and are associated with health and longevity.

Link: https://www.eurekalert.org/pub_releases/2020-07/uosc-smh070920.php

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