Journal
NEURON
Volume 83, Issue 2, Pages 331-343Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2014.06.016
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Funding
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- Bertarelli Foundation
- NIH [R01 NS038253, P30 HD018655, RO1 AG033053, UO1 HL100402, NS069375, T32 HD007249]
- NIH NRSA [F31 AG042227-02, S10RR027431-01]
- Stanford MSTP and School of Medicine
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The regenerative capacity of the peripheral nervous system declines with age. Why this occurs, however, is unknown. We demonstrate that 24-month-old mice exhibit an impairment of functional recovery after nerve injury compared to 2-month-old animals. We find no difference in the intrinsic growth capacity between aged and young sensory neurons in vitro or in their ability to activate growth-associated transcriptional programs after injury. Instead, using age-mismatched nerve transplants in vivo, we show that the extent of functional recovery depends on the age of the nerve graft, and not the age of the host. Molecular interrogation of the sciatic nerve reveals that aged Schwann cells (SCs) fail to rapidly activate a transcriptional repair program after injury. Functionally, aged SCs exhibit impaired dedifferentiation, myelin clearance, and macrophage recruitment. These results suggest that the age-associated decline in axonal regeneration results from diminished Schwann cell plasticity, leading to slower myelin clearance.
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