Yue‑Yan Cen1,2 · Mu‑Yun Wang1,2 · Qin‑Xuan Song1,2 · Xin‑Lin Gao1,2 · Cheng Zhou3  · Chun‑Jie Li1,4 · Fei Liu1,2 · Yan‑Yan Zhang1,2  · Jie‑Fei Shen1,2

1 State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, National Center for Stomatology, West China School of Stomatology, Sichuan University, Chengdu 610041, China 

2 Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China 

3 Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital of Sichuan University, Chengdu, China 

4 Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China

Abstract

Peripheral nerve injury (PNI) significantly impairs patients’ quality of life, with elderly individuals experiencing particularly severe consequences due to aging-related declines in neuronal injury response and repair capabilities. Processes of the generation and transmission of injury signals, axonal disruption, initiation of regeneration, and the elongation of regenerating axons, as well as the subsequent reinnervation by these axons, are all significantly influenced by aging. These alterations are closely associated with changes in mitochondrial function, neuronal transport systems, a persistent inflammatory milieu, and various microenvironmental non-neuronal cells. Therefore, this review synthesized the pivotal role of aging in the multifaceted regulation of the nervous system following PNI and highlighted promising molecular regulatory mechanisms in the signaling pathways. Furthermore, it identified critical areas for future research, including unresolved questions in age-associated injury responses, potential targets for pharmacological intervention, and emerging therapeutic strategies meriting consideration for research and development.

Keywords

Aging; Injury; Neural regeneration; Mitochondria; Axonal transport

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