About six weeks ago, a glass shattered in my hand, severing the nerve in my pinky finger. The feeling in my fingertip still hasn’t returned, and now I know why: I’m too old.
Going back to World War II, it’s been speculated that recovery of peripheral nerve injuries—like those in limbs and extremities—is influenced by age. And studies indicate that peripheral neuropathy is common in people over 65, including those who have received cancer chemotherapy, and often unexplained.
“When you’re very young, the system is very plastic and able to regenerate,” Michio Painter told me recently. He is a graduate student in the laboratory of Clifford Woolf, PhD, director of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital. “After that, there’s a gradual decline. By the age of 30, much of this plasticity is gone.”
Traditionally, this decline has been thought to reflect age-related differences in neurons’ ability to regrow, but when Painter studied neurons in a dish, he couldn’t confirm this.
“We were surprised to see that old neurons were able to grow just fine,” he says. When they looked at gene activation in injured sensory neurons, all of the right growth signals seemed to switch on.
So why do I still have this dead spot of feeling—and weird electrical sensations in the part of my finger cut by the glass?
Painter first speculated that older people might lack nerve-rejuvenating factors in their blood. This idea of “young blood” has some precedent: Several recent studies found that exposing older mice to the blood of younger mice made them last longer on the treadmill, increased blood flow in the brain and boosted performance on learning and memory tests.
Not so for peripheral nerve injuries, however.
“What we found was that the blood had no effect,” says Painter. “We then figured there must be something in the nerve environment itself that’s modulating the ability of the nerve to regenerate.”
He and his colleagues did a series of experiments, published last month in Neuron, working with both old and young mice. An old (24-month-old) mouse with a nerve injury recovered like a young (2-month-old) mouse if young nerve tissue was grafted on. But when a young injured mouse received nerve tissue from an older mouse, regeneration was severely reduced.
Eventually, they realized the missing link: In older mice, it was glial cells that were failing, not the neurons.
In particular, Schwann cells, a type of glial cell in the peripheral nervous system, were defective. Normally, Schwann cells do three things to encourage axon regrowth after injury. First, they clear the area of myelin, the insulating coating on axons that is thought to inhibit regeneration after injury. Second, they form tracts—similar to roadways—along which axons can regrow. Third, they secrete growth factors that stimulate regeneration.
“That entire process was not happening as efficiently in the old mice,” says Painter.
Though many dots need to be connected, the findings open a new avenue for promoting nerve regeneration—at least for peripheral nerves. Perhaps young Schwann cells could be transplanted into older patients. Or perhaps chemical factors could be introduced to kick-start Schwann cell function. Other neuroscience research is converging on the importance of glial cells and glia-derived factors.
Painter, who has left Boston Children’s to start his postdoctoral fellowship at the Harvard Stem Cell Institute, hopes to explore what is causing the age-related defects in Schwann cells and whether the same defects start to accumulate in other kinds of glial cells, like those in the brain. “That would be very important in the context of neurodegenerative disorders like Alzheimer’s disease,” he says.
If so, I’d consider donating my poorly healing pinky to science.