AGE-RELATED DEGENERATION OF SMALL SENSORY AND AUTONOMIC FIBERS AND THEIR TARGET STRUCTURES IN ELDERLY HUMAN SKIN

Small fiber neuropathy (SFN) affects C and Aδ sensory fibers as well as autonomic fibers, with intraepidermal nerve fiber density (IENFD) serving as the diagnostic standard. The impact of aging on small fiber integrity and the structures they innervate, epidermis, dermis, sweat glands, and microvasculature, remains poorly understood. This study aimed to characterize age-related alterations of small fibers and their target structures in octogenarian skin.
Six bilateral distal-leg skin biopsies from elderly donors (mean age 79.7 ± 7.1 years; 4 females, 2 males) were analyzed using immunofluorescence for PGP 9.5 (pan-neuronal), TRPV1 (nociceptive), tyrosine hydroxylase (sympathetic/autonomic), S100β (melanocytes and glial cells), and Collagen IV (vascularization). IENFD was quantified with ImageJ. Autonomic innervation of sweat glands was assessed, and fiber distribution relative to vascular and glandular structures was examined.
Mean IENFD was 7.64 ± 2.59 fibers/mm, below normative values for healthy adults aged 20-40 years (8-12 fibers/mm). Autonomic sweat gland innervation averaged 929.14 ± 298.78 AU, reduced compared with young adult controls. S100β staining showed abundant melanocytes and sparse dermal fibers, Tyrosine hydroxylase highlighted several sweat glands, some co-expressing TRPV1, which was also detected in dermal microvessel.
These findings reveal marked degeneration of small sensory fibers in octogenarians, with relative preservation of autonomic and vascular innervation, highlighting the selective vulnerability of epidermal innervation. These findings highlight the selective vulnerability of epidermal innervation during aging and provide structural correlations relevant to SFN in the elderly.