News from the old: Aging features in the intracardiac, musculoskeletal, and enteric nervous systems

Abstract

Aging strongly affects the peripheral nervous system (PNS), triggering alterations that vary depending on the innervated tissue. The most frequent alteration in peripheral nerve aging is reduced nerve fiber and glial density which can lead to abnormal nerve functionality. Interestingly, the activation of a destructive phenotype takes place in macrophages across the PNS while a reduced number of neuronal bodies is a unique feature of some enteric ganglia. Single cell/nucleus RNA-sequencing has unveiled a striking complexity of cell populations in the peripheral nerves, and these refined cell type annotations could facilitate a better understanding of PNS aging. While the effects of senescence on individual PNS cell types requires further characterization, the use of senolytics appears to improve general PNS function in models of aging. Here, we review the current understanding of age-related changes of the intracardiac, musculoskeletal, and enteric nervous system sub-sections of the PNS, highlighting their commonalities and differences.