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Age-related decline in nuclear envelope LINC complex drives neuronal aging via axon initial segment dysfunction - PubMed

4 hours ago
  • #neuronal aging
  • #LINC complex
  • #axon initial segment
  • Aging reduces LINC complex expression, especially Sun1, on the nuclear envelope in neurons, causing axon initial segment (AIS) shortening and impaired excitability.
  • Maintaining Sun1 expression in aged neurons rescues nuclear structure, chromatin dynamics, and gene expression, restoring AIS function and critical ion channels.
  • Disrupting the LINC complex in young mice mimics aging effects, damaging AIS integrity, reducing neuronal excitability, and leading to brain dysfunction.
  • Administering Sun1 to aged neurons prevents AIS shortening and excitability decline, revealing a key mechanism in normal brain aging and potential therapeutic target.