Long before the usual physiological signs, the withering of neurons and the gradual atrophy of the brain, that tip doctors off to the presence of a neurodegenerative disease, there’s already something different about their patients’ brain cells. Action potentials flash across a long, thin arm protruding from the cell body in a healthy neuron, and spread through what look like tiny fingers to find the synapses, where the tiny fingers of other neurons meet it. But advancing age and neurodegeneration cause these arms–called axons–to begin to disintegrate, halting communication between neurons.
We’ve been able to thwart this process in animal models by downregulating insulin signaling, which can be accomplished through caloric restriction, among other things. This method requires the protein FOXO, which, along with its invertebrate counterpart DAF-16, has been linked time and again to longevity, but the mechanisms governing its anti-aging effects still aren’t totally clear. Intriguingly, FOXO shows higher levels of expression in aging brains, possibly as a protective response to increasing inflammation.
So what do you do when you have a protein that you know is important, but you don’t really know why? Well, naturally, you engineer some mice without it.
Since FOXO 1, 3 and 4 aren’t essential for
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