Influence of aging on peripheral nerve function and regeneration

Abstract

Aging deeply influences several morphologic and functional features of the peripheral nervous system (PNS). Morphologic studies have reported a loss of myelinated and unmyelinated nerve fibers in elderly subjects, and several abnormalities involving myelinated fibers, such as demyelination, remyelination and myelin balloon figures. The deterioration of myelin sheaths during aging may be due to a decrease in the expression of the major myelin proteins (P0, PMP22, MBP). Axonal atrophy, frequently seen in aged nerves, may be explained by a reduction in the expression and axonal transport of cytoskeletal proteins in the peripheral nerve. Aging also affects functional and electrophysiologic properties of the PNS, including a decline in nerve conduction velocity, muscle strength, sensory discrimination, autonomic responses, and endoneurial blood flow. The age-related decline in nerve regeneration after injury may be attributed to changes in neuronal, axonal, Schwann cell and macrophage responses. After injury, Wallerian degeneration is delayed in aged animals, with myelin remnants accumulated in the macrophages being larger than in young animals. The interaction between Schwann cells and regenerative axons takes longer, and the amount of trophic and tropic factors 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 animals. Aging also determines a reduction in terminal and collateral sprouting of regenerated fibers, further limiting the capabilities for target reinnervation and functional restitution. These age-related changes are not linearly progressive with age; the capabilities for axonal regeneration and reinnervation are maintained throughout life, but tend to be delayed and less effective with aging.

Reduced thermal sensitivity and Nav1.8 and TRPV1 channel expression in sensory neurons of aged mice

“…In the peripheral target, measures in human of intraepidermal nerve fiber density showed no significant change in epidermal fiber density with age, except when comparison of aged samples was made to the highest values in the youngest subjects [25,27] (though see [7,14]). In 18-month old mice, innervation to the epidermis showed only a moderate loss (10-15%) in nerve fiber density [37]. Interestingly, this loss of peripheral nerve fibers in very old rodents does not appear to reflect a loss of neurons in cervical and lumbar DRG.…”

“…Functional studies in several species have shown that impairment of cutaneous sensitivity occurs with aging [13,37]. This age-related decrease in sensitivity can reduce tactile perception, detection of noxious stimuli and tissue injury.…”

“…To identify how these degenerative changes occur, several studies of human and rodent have compared electrophysiological and anatomical properties of young and aged neurons, peripheral nerves and target tissues. In humans, electrophysiological measures have found lower nerve conduction velocity in older individuals, suggesting impairment in axon structure and function [9,37]. Analysis of nerve fibers in aging mice from 20 months of age onward, showed both myelinated and unmyelinated fibers to be reduced in number, which in the very old mouse (33 months) approaches 50% loss [13].…”

Aging effects on joint proprioception: the role of physical activity in proprioception preservation

“…The conclusions drawn from these studies suggest that proprioception decreases with aging is in part because of changes in muscle spindle function. In addition to that, advancing age leads to deficits in the processing of sensory input (myelin abnormalities, axonal atrophy, and declined nerve conduction velocity) [7,24,59,74] and neuromuscular performance decline. It has been shown that the older adult has fewer, but on average larger and slower motor units, resulting in motor unit reorganization [9,14,40,65,66].…”

Neural control of aging skeletal muscle

“…The deterioration of myelin sheaths during aging may be due to a decrease in the expression of the major myelin proteins (P0, PMP22, MBP). Axonal atrophy, frequently seen in aged nerves, may be explained by a reduction in the expression and axonal transport of cytoskeletal proteins in the peripheral nerve (Verdu et al ., 2000). The incidence and severity of the age-related peripheral nerve changes seems to depend on the animal's genetic background.…”