New Finding May Compromise Aging Studies

Some studies on the genetic roots of aging will need a second look after the discovery that a common lab chemical can extend the life span of female fruit flies by 68 percent.

For years, scientists have engineered fruit flies whose genes can be turned on and off by a synthetic hormone, allowing detailed studies of the effects of single genes on life span. Many of the genes have close relatives in humans.

Unfortunately, the hormone used to perform the studies turns out to be anything but neutral.

John Tower, professor of biological sciences, had been studying genetic causes of aging by turning genes off and on in flies. He and lab member Gary Landis grew suspicious of the hormone that they and others were using to activate the genes — mifepristone, a synthetic chemical known to terminate pregnancy in humans.

Many studies have shown that reproduction shortens lifespan in flies and other organisms. Tower and coworkers wondered if the hormone they were using could be affecting reproduction in flies, and in turn their life span.

An example of gene-switching — in this case, used to drive Green Fluorescent Protein (GFP) expression in the fat tissue of the fly on the right. Photo courtesy of John Tower.

They discovered that flies exposed to the hormone laid only half the usual amount of eggs — and lived 68 percent longer, from a median age of 56 to 94 days.

The mifepristone had little or no effect on the life expectancy of female flies that had not mated, which had an even better overall survival rate and maximum lifespan.

Tower and his team recently published their findings in the journal Aging.

“This opens up a new line of inquiry for longevity studies, and identifies candidate genes and mechanisms for regulating the trade-off between reproduction and lifespan that may be shared with humans,” Tower said. “It also means, however, that our earlier longevity studies that relied on mifepristone as a gene switch will need to be re-evaluated.”

The study, co-authored by USC’s Gary N. Landis, Matthew P. Salomon, Daniel Keroles, Nicholas Brookes, and Troy Sekimura, was funded by a grant from the Department of Health and Human Services, National Institute on Aging (AG011833) and by pilot project funding from the Southern California Environmental Health Sciences Center (5P30ES007048).

The study can be found online at http://www.impactaging.com/papers/v7/n1/full/100721.html.