Mifepristone, which is also used to treat Cushing's disease and certain cancers, has caught the attention of scientists exploring ways to promote longer, healthier lives. In a study involving fruit flies, John Tower, professor of biological sciences at USC Dornsife, compared the effects of mifepristone to rapamycin, a drug that has demonstrated the ability to increase the lifespan of a variety of animals.
The study, published in the journal Fly, showed that both drugs independently extended the lifespan of fruit flies. Interestingly, combining the two drugs does not offer additional benefits and slightly reduced lifespan, suggesting they both act through the same biological pathway.
To understand how mifepristone and rapamycin might extend lifespan, researchers focused on mitophagy. Mitophagy is like a cellular "cleanup" process in which damaged or dysfunctional mitochondria - the cell's energy producers - are broken down and recycled. Impaired mitophagy has been linked to aging and age-related diseases, while increased mitophagy is believed to be a factor in rapamycin's life-extending effects.
For the first time, the researchers were able to noninvasively measure mitophagy in fruit flies. They found that mifepristone increased mitophagy to the same extent as rapamycin.
"The noninvasive in vivo mitophagy assay is novel, and our findings suggest that enhancing mitochondrial health could be central to how both drugs extend lifespan," Tower said.
The fact that mifepristone - a drug already approved for various medical uses - can boost mitophagy points to its potential as an anti-aging treatment, added Tower, whose’s previous research has shown anti-aging benefits from the drug. Because it is already approved, repurposing mifepristone for anti-aging clinical trials could be faster, potentially accelerating the development of new longevity therapies.
Future research will need to determine whether the effects observed in fruit flies can be replicated in humans, said Tower. If so, mifepristone might provide a relatively accessible and safe way to reduce age-related cellular decline, paving the way for other therapies that enhance mitochondrial health to support longevity.
Landis GN, Baybutt B, Das S, Fan Y, Olsen K, Yan K, Tower J.
Mifepristone and rapamycin have non-additive benefits for life span in mated female Drosophila.
Fly (Austin). 2024 Dec;18(1):2419151. doi: 10.1080/19336934.2024.2419151