A novel genetic manipulation significantly extends the life spans of flies by reducing the amount of wear and tear suffered by nerve cells in adults, according to new work published in Cell Metabolism. The findings support the idea that therapies designed to protect the adult nervous system by curbing the production of damaging free radicals might effectively increase longevity in other animals, including humans, the researchers said.
"We've identified a new point of intervention for extending life span by adjusting the amount of oxidative damage to nerve cells," said Stephen Helfand of the University of Connecticut Health Center in Farmington. Oxidative damage by free radicals is thought to be one of the primary forces driving the process of aging and determining life span, he added.
Free radicals, or reactive oxygen species (ROS), are a normal byproduct of energy production in the membrane bound cellular powerhouses known as mitochondria. Mitochondria produce chemical energy by setting up a gradient of hydrogen atoms, or protons, across their inner membranes. In the process, free radicals are generated.
Once the proton gradient is sufficiently established, protons begin to flow back across the membrane through a special enzyme that harnesses the energy released in the form of ATP molecules. However, so-called mitochondrial uncoupling proteins (UCPs) allow some of the protons to leak into the matrix, thus disrupting the electrochemical gradient and partially "uncoupling" proton flow from ATP synthesis. Mitochondrial uncoupling, in turn, lowers the membrane potential, decreases ATP production, and increases metabolic rate, among other functions that vary among tissues.