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.
In flies, dawdle had been shown to affect neural development. In humans, one use for activin is that the brain employs it to stimulate ovarian follicles in the menstrual cycle of the female reproductive system.
But when the team went searching for where in the flies dawdle mattered to life span, their experiments showed that it was in muscle.
What was it doing there? Their 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.
In addition, the team found a potential linkage to other tissues when they discovered that suppressing dawdle also reduced insulin secretion from the insulin producing cells (IPCs) in the brains of the flies. This eventually led to a reduction in systemic insulin signaling. This completed a feedback loop in which reduced insulin signaling allows more dFOXO to suppress dawdle, in turn leading to further suppression of insulin secretion from the brain. That same process also allowed for better muscle maintenance by promoting expression of Atg8a.
Not dawdling in the l
|Contact: David Orenstein|