Evidence for loss of myelinated input to the spinal cord in senescent rats.

Impaired sensory perception is a well-established stigma of aging and whereas loss of dorsal root ganglion (DRG) neurons is marginal there is a specific pattern of reduced peripheral sensory innervation. To resolve if similar regressive processes occur in the central innervation, peripheral nerves were injected with markers for unmyelinated (isolectin B4) or myelinated (cholera toxin B subunit; CTB) DRG neurons. The results were a dramatic decrease of primary sensory endings in the spinal cord of aged rats following transganglionic labeling with CTB, and also to a lesser degree with B4. Profile counting and frequency estimates showed that the reduction of CTB labeled profiles not was caused by impaired axonal uptake, slowed axonal transport of CTB, or by a loss of myelinated fibers in the peripheral nerve. At the ultrastructural level, peripheral nerves showed the classical hallmarks of aging, with more pronounced alterations in myelinated than unmyelinated axons. Taken together, sensory deprivation in senescence appears to be a distal process in DRG neurons involving both peripheral and central target disconnection. Finally, preliminary data indicates that the substantial reduction in mechanoreceptive input to the central nervous system co-varies with the degree of sensorimotor impairment of the aged individuals.