Influence of aging on peripheral nerve function and regeneration

Aging deeply influences several morphologic and functional features of the peripheral nervous system (PNS). Morphologic studies have reported a loss o f myelinated and unmyelinated nerve fibers in elderly subjects, and several abnormalities involving myelinated fibers, such as demyelination, remyelin ation and myelin balloon figures. The deterioration of myelin sheaths durin g aging may be due to a decrease in the expression of the major myelin prot eins (P0, PMP22, MBP). Axonal atrophy, frequently seen in aged nerves, may be explained by a reduction in the expression and axonal transport of cytos keletal proteins in the peripheral nerve. Aging also affects functional and electrophysiologic properties of the PNS, including a decline in nerve con duction velocity, muscle strength, sensory discrimination, autonomic respon ses, and endoneurial blood flow. The age-related decline in nerve regenerat ion after injury may be attributed to changes in neuronal, axonal, Schwann cell and macrophage responses. After injury, Wallerian degeneration is dela yed in aged animals, with myelin remnants accumulated in the macrophages be ing larger than in young animals. The interaction between Schwann cells and regenerative axons takes longer, and the amount of trophic and tropic fact ors secreted by reactive Schwann cells and target organs are lower in older subjects than they are in younger subjects,The rate of axonal regeneration becomes slower and the density of regenerating axons decrease in aged anim als. Aging also determines a reduction in terminal and collateral sprouting of regenerated fibers, further limiting the capabilities for target reinne rvation and functional restitution. These age-related changes are not linea rly progressive with age; the capabilities for axonal regeneration and rein nervation are maintained throughout life, but tend to be delayed and less e ffective with aging.