Scientists at a university in United States’ Southern California may have found the beginnings of a path needed to extend the lifespan of human beings.
The research by a team from USC Dornsife College of Letters, Arts and Sciences, published on July 10 by the Journal of Gerontology: Biological Sciences, shows the drug mifepristone can extend the lives of two very different species used in laboratory studies.
Clinicians use mifepristone, also known as RU-486, to end early pregnancies as well as to treat cancer and Cushing disease.
The study, Metabolic Signatures of Life Span Regulated by Mating, Sex Peptide and Mifepristone/RU486 in Female Drosophila, also suggests that the findings may apply to other species, including humans.
John Tower, a professor of biological sciences at USC Dornsife College of Letters, Arts and Sciences, and his team found mifepristone extends the lives of the female fruit fly Drosophila that have mated.
Female fruit flies receive sex peptide from males during mating and previous research has shown that the molecule causes inflammation and reduces the health and lifespan of female flies.
Giving 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, Tower and his team, including Gary Landis, a senior research associate and the lead researcher on the study, found.
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,” Tower said. “In the human, we know that mifepristone decreases reproduction and alters innate immune response, so might it also increase life span?” Tower was quoted as saying by News Medical, an open-access medical and life science hub.
The team looked at the genes, molecules and metabolic processes that changed when flies were fed the drug to seek a better understanding of how mifepristone works to increase lifespan.
They found that a molecule called juvenile hormone, which regulates the development of fruit flies throughout their life, from egg to larvae to adult, plays a central role.
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. The metabolic shift promotes harmful inflammation and it appears to make the flies more sensitive to toxic molecules produced by bacteria in their microbiome, the study shows.
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. Tower has said that these metabolic pathways are conserved in humans and are associated with health and longevity, according to News Medical.
Tower and his collaborators also gave the same drug to C elegans, a small roundworm, and found that mifepristone had the same life-extending effect on the mated worm.
He said because Drosophila fruit flies and C elegans worms are relatively distant in terms of evolution, the similar results in such different species suggest other organisms, including humans, might see comparable benefits to lifespan.
He said the fact that mifepristone can increase lifespan in both species suggests the mechanism is important to many species.
“Our data show that in Drosophila, mifepristone either directly or indirectly counteracts juvenile hormone signalling, but the exact target of mifepristone remains elusive,” Tower said, according to News Medical.
A clearer understanding of the intricacies of mifepristone’s actions is needed before drawing any firm conclusions, Tower added.
