Senescent Schwann cells induced by aging and chronic denervation impair axonal regeneration after peripheral nerve injury
Senescent Schwann cells induced by aging and chronic denervation impair axonal regeneration after peripheral nerve injury
Abstract After peripheral nerve injuries, successful axonal growth and functional recovery requires the reprogramming of Schwann cells into a reparative phenotype, a process dependent on the activation of the transcription factor c-Jun. Nevertheless, axonal regeneration is greatly impaired in aged organisms or after chronic denervation leading to important clinical problems. This regenerative failure has been associated to a diminished c-Jun expression by Schwann cells, but whether the inability of these cells to maintain a repair state is associated to the transition into a phenotype inhibitory for axonal growth, has not been evaluated so far. We find that repair Schwann cells transitions into a senescent phenotype, characterized by diminished c-Jun expression and secretion of factor inhibitory for axonal regeneration in both aging and chronic denervation. In both conditions, elimination of senescent Schwann cells by systemic senolytic drug treatment or genetic targeting improves nerve regeneration and functional recovery in aging and chronic denervation, associated with an upregulation of c-Jun expression and a decrease in nerve inflammation. This work provides the first characterization of senescent Schwann cells and their impact over axonal regeneration in aging and chronic denervation, opening new avenues for enhancing regeneration, and functional recovery after peripheral nerve injuries.
Geschwind Daniel、Campisi Judith、Court Felipe A.、Patel Sandip Kumar、Bons Joanna、Fuentes-Flores Andr¨|s、Geronimo-Olvera Cristian、?ecu?ir David、Gomez-Sanchez Jose A.、Hoke Ahmet、Wright Megan C.、Schilling Birgit
Departments of Neurology, Psychiatry, and Human Genetics, David Geffen School of Medicine, University of CaliforniaBuck Institute for Research on AgingCenter for integrative Biology, Universidad Mayor||FONDAP Geroscience Center for Brain Health and Metabolism||Buck Institute for Research on AgingBuck Institute for Research on AgingBuck Institute for Research on AgingCenter for integrative Biology, Universidad Mayor||FONDAP Geroscience Center for Brain Health and MetabolismCenter for integrative Biology, Universidad Mayor||FONDAP Geroscience Center for Brain Health and MetabolismCenter for integrative Biology, Universidad Mayor||FONDAP Geroscience Center for Brain Health and MetabolismInstituto de Investigaci¨?n Sanitaria y Biom¨|dica de Alicante (ISABIAL)||Instituto de Neurociencias de AlicanteDepartments of Neurology and Neuroscience, Johns Hopkins School of MedicineDepartments of Neurology and Neuroscience, Johns Hopkins School of MedicineBuck Institute for Research on Aging
神经病学、精神病学基础医学生物科学研究方法、生物科学研究技术
Geschwind Daniel,Campisi Judith,Court Felipe A.,Patel Sandip Kumar,Bons Joanna,Fuentes-Flores Andr¨|s,Geronimo-Olvera Cristian,?ecu?ir David,Gomez-Sanchez Jose A.,Hoke Ahmet,Wright Megan C.,Schilling Birgit.Senescent Schwann cells induced by aging and chronic denervation impair axonal regeneration after peripheral nerve injury[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2022.12.07.519441.点此复制
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