They uncovered a complicated chain of molecular events that leads from insulin to protein degradation in muscles and significantly diminished life span in fruit flies.
The central feature of the study is the newly discovered role of the fruit fly equivalent of the mammalian protein complex activin. They found that it blocks the natural mechanism in muscle cells for cleaning out misfolded proteins, leading to a decline in muscle performance.
It was found that blocking the activity of that activin equivalent, called dawdle, can lengthen a fly's life span by as much as 20 percent, about 10 days.
What excites the researchers is not that they can allow flies to stick around another week or two, but that the same fundamental proteins they have implicated in flies are "conserved" in evolution, meaning they also operate in mammals including humans.
"The ultimate goal of our research is to understand how certain molecular signaling pathways control aging across all species in general," said study lead author Hua Bai, a postdoctoral researcher in the ecology and evolutionary biology lab of Marc Tatar, professor of biology at Brown. "For now this research is in fruit flies, but we think it can be extended to human aging biology. This signaling is quite conserved evolutionarily."
The researchers began the study armed with the understanding that a reduction in insulin signaling lengthens fly life span because when there is less insulin there is more of a protein called dFOXO.
Bai narrowed his search from hundreds of genes down to just three. He used interference RNA to suppress them and found that doing so increased life span in the flies. Suppressing dawdle (the fly version of activin) increased life span by 12 to 35 percent.
The experiments revealed that dawdle suppresses the activity of a gene called Atg8a, whose job is to spur the process of "autophagy" - the cleanup of misfolded proteins. A buildup of those misfolded proteins weakens muscle tissue, much like a buildup of misfolded proteins in brain cells is believed to cause Alzheimer's disease. When researchers suppressed dawdle, more misfolded proteins were cleared from muscle fibers.
The researchers also found that overexpressing Atg8a in the muscle of flies lengthened life span somewhat.
The study is published in PLoS Genetics.