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

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Abstract: 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.

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Bibliographic citation: Senescent Schwann cells induced by aging and chronic denervation impair axonal regeneration following peripheral nerve injury ; day:20 ; month:10 ; year:2023 ; extent:25
EMBO molecular medicine / European Molecular Biology Organization ; (20.10.2023) (gesamt 25)

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

DOI: 10.15252/emmm.202317907

URN: urn:nbn:de:101:1-2023102015311155832194

Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 14.08.2025, 10:48 AM CEST

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Associated

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

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

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Other Objects (12)

Schwann cells restrict axonal diameters via CMTM6

Intraarticular senescent chondrocytes impair the cartilage regeneration capacity of mesenchymal stem cells

Taxanes and platinum derivatives impair Schwann cells via distinct mechanisms

Neurofilament accumulations in amyotrophic lateral sclerosis patients’ motor neurons impair axonal initial segment integrity

Sensory neuropathy-causing mutations in ATL3 affect ER–mitochondria contact sites and impair axonal mitochondrial distribution

Fingolimod attenuates experimental autoimmune neuritis and contributes to Schwann cell-mediated axonal protection

Skeletal myotubes expressing ALS mutant SOD1 induce pathogenic changes, impair mitochondrial axonal transport, and trigger motoneuron death

Immunoglobulins stimulate cultured Schwann cell maturation and promote their potential to induce axonal outgrowth

A Review on the Role of Endogenous Neurotrophins and Schwann Cells in Axonal Regeneration

Upregulated lncARAT in Schwann cells promotes axonal regeneration by recruiting and activating proregenerative macrophages

Carotid chemoreceptor denervation does not impair hypoxia-induced thermal downregulation but vitiates recovery from a hypothermic and hypometabolic state in mice

Single senescent cell sequencing reveals heterogeneity in senescent cells induced by telomere erosion

Schwann cells restrict axonal diameters via CMTM6

Intraarticular senescent chondrocytes impair the cartilage regeneration capacity of mesenchymal stem cells

Taxanes and platinum derivatives impair Schwann cells via distinct mechanisms

Neurofilament accumulations in amyotrophic lateral sclerosis patients’ motor neurons impair axonal initial segment integrity

Sensory neuropathy-causing mutations in ATL3 affect ER–mitochondria contact sites and impair axonal mitochondrial distribution

Fingolimod attenuates experimental autoimmune neuritis and contributes to Schwann cell-mediated axonal protection

Skeletal myotubes expressing ALS mutant SOD1 induce pathogenic changes, impair mitochondrial axonal transport, and trigger motoneuron death

Immunoglobulins stimulate cultured Schwann cell maturation and promote their potential to induce axonal outgrowth

A Review on the Role of Endogenous Neurotrophins and Schwann Cells in Axonal Regeneration

Upregulated lncARAT in Schwann cells promotes axonal regeneration by recruiting and activating proregenerative macrophages

Carotid chemoreceptor denervation does not impair hypoxia-induced thermal downregulation but vitiates recovery from a hypothermic and hypometabolic state in mice

Single senescent cell sequencing reveals heterogeneity in senescent cells induced by telomere erosion

Schwann cells restrict axonal diameters via CMTM6

Intraarticular senescent chondrocytes impair the cartilage regeneration capacity of mesenchymal stem cells

Taxanes and platinum derivatives impair Schwann cells via distinct mechanisms

Neurofilament accumulations in amyotrophic lateral sclerosis patients’ motor neurons impair axonal initial segment integrity

Sensory neuropathy-causing mutations in ATL3 affect ER–mitochondria contact sites and impair axonal mitochondrial distribution

Fingolimod attenuates experimental autoimmune neuritis and contributes to Schwann cell-mediated axonal protection

Skeletal myotubes expressing ALS mutant SOD1 induce pathogenic changes, impair mitochondrial axonal transport, and trigger motoneuron death

Immunoglobulins stimulate cultured Schwann cell maturation and promote their potential to induce axonal outgrowth

A Review on the Role of Endogenous Neurotrophins and Schwann Cells in Axonal Regeneration

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Carotid chemoreceptor denervation does not impair hypoxia-induced thermal downregulation but vitiates recovery from a hypothermic and hypometabolic state in mice

Single senescent cell sequencing reveals heterogeneity in senescent cells induced by telomere erosion

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