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.

Inflammaging impairs peripheral nerve maintenance and regeneration

“…Engaging several methods, we set out to comprehensively describe age‐dependent changes on functional, structural, cellular, and molecular levels. Our experimental design confirmed and further detailed previous work in this area (Figures 1 and 2) (He, Yadgarov, Sharif, & McCluskey, 2012; Painter et al, 2014; Scheib & Hoke, 2016; Verdu et al, 2000). …”

“…A growing body of work demonstrates age‐dependent decline of peripheral nerve regeneration capacity (Painter et al, 2014; Verdu et al, 2000; Wang et al, 2007), but insight into underlying mechanisms remains limited. To better understand age‐dependent factors impacting on peripheral nerve regeneration, we performed sciatic nerve crush injuries on C57BL/6 J mice of two different ages.…”

“…This regenerative potential decreases in mammals of advanced age; peripheral nerve repair becomes slow, incomplete, and/or nonfunctional (Verdu, Ceballos, Vilches, & Navarro, 2000; Wang, Zhou, Shi, Smith, & Li, 2007). While this defect has long been described in humans and rodent model systems, progress in understanding molecular and cellular mechanisms underlying PNS aging is limited—hampering the development of rational rejuvenating therapies in aged patients.…”

Effect of Age, Sex and Gender on Pain Sensitivity: A Narrative Review

“…There is some debate in the literature about the occurrence of physiological alteration in the processing of nociception and pain, which can be ascribed to age [2,40,41]. It is clearly evident that there is a high prevalence of chronic pain in the elderly, and this can be attributed partly to the physiological changes of peripheral and central [38]; pain mechanisms and to changes in some psychological attitudes towards pain [41]. It has been reported that changes in sensations and perceptions in sensory systems occur in the elderly [42].…”

“…A large amount of the literature on the neurobiology of aging suggests that there is a widespread and considerable alteration in the structure, function, and biochemistry of the peripheral [13,37,38] and central nervous system [13] structures of older individuals. It has been documented that there is a decrease in the density of myelinated fibres with aging [43 -45].…”