Biomaterial Database

Senescent Schwann cells induced by aging and chronic denervation impair axonal regeneration following peripheral nerve injury. 2023

Andrés Fuentes-Flores, and Cristian Geronimo-Olvera, and Karina Girardi, and David Necuñir-Ibarra, and Sandip Kumar Patel, and Joanna Bons, and Megan C Wright, and Daniel Geschwind, and Ahmet Hoke, and Jose A Gomez-Sanchez, and Birgit Schilling, and Daniela L Rebolledo, and Judith Campisi, and Felipe A Court

Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile.

Following peripheral nerve injury, successful axonal growth and functional recovery require Schwann cell (SC) reprogramming into a reparative phenotype, a process dependent upon c-Jun transcription factor activation. Unfortunately, axonal regeneration is greatly impaired in aged organisms and following chronic denervation, which can lead to poor clinical outcomes. While diminished c-Jun expression in SCs has been associated with regenerative failure, it is unclear whether the inability to maintain a repair state is associated with the transition into an axonal growth inhibition phenotype. We here find that reparative SCs transition into a senescent phenotype, characterized by diminished c-Jun expression and secretion of inhibitory factors for axonal regeneration in aging and chronic denervation. In both conditions, the elimination of senescent SCs by systemic senolytic drug treatment or genetic targeting improved nerve regeneration and functional recovery, increased c-Jun expression and decreased nerve inflammation. This work provides the first characterization of senescent SCs and their influence on axonal regeneration in aging and chronic denervation, opening new avenues for enhancing regeneration and functional recovery after peripheral nerve injuries.

UI	MeSH Term	Description	Entries
D003714	Denervation	The resection or removal of the nerve to an organ or part.	Laser Neurectomy,Neurectomy,Peripheral Neurectomy,Radiofrequency Neurotomy,Denervations,Laser Neurectomies,Neurectomies,Neurectomies, Laser,Neurectomies, Peripheral,Neurectomy, Laser,Neurectomy, Peripheral,Neurotomies, Radiofrequency,Neurotomy, Radiofrequency,Peripheral Neurectomies,Radiofrequency Neurotomies
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368	Aged	A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available.	Elderly
D000375	Aging	The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.	Senescence,Aging, Biological,Biological Aging
D012583	Schwann Cells	Neuroglial cells of the peripheral nervous system which form the insulating myelin sheaths of peripheral axons.	Schwann Cell,Cell, Schwann,Cells, Schwann
D059348	Peripheral Nerve Injuries	Injuries to the PERIPHERAL NERVES.	Peripheral Nerve Injury,Nerve Injuries, Peripheral,Nerve Injury, Peripheral