Hypothalamic Sirt1 protects terminal Schwann cells and neuromuscular junctions from age-related morphological changes

Alison K. Snyder-Warwick, Akiko Satoh, Katherine B. Santosa, Shin ichiro Imai, Albina Jablonka-Shariff

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)


Neuromuscular decline occurs with aging. The neuromuscular junction (NMJ), the interface between motor nerve and muscle, also undergoes age-related changes. Aging effects on the NMJ components—motor nerve terminal, acetylcholine receptors (AChRs), and nonmyelinating terminal Schwann cells (tSCs)—have not been comprehensively evaluated. Sirtuins delay mammalian aging and increase longevity. Increased hypothalamic Sirt1 expression results in more youthful physiology, but the relationship between NMJ morphology and hypothalamic Sirt1 was previously unknown. In wild-type mice, all NMJ components showed age-associated morphological changes with ~80% of NMJs displaying abnormalities by 17 months of age. Aged mice with brain-specific Sirt1 overexpression (BRASTO) had more youthful NMJ morphologic features compared to controls with increased tSC numbers, increased NMJ innervation, and increased numbers of normal AChRs. Sympathetic NMJ innervation was increased in BRASTO mice. In contrast, hypothalamic-specific Sirt1 knockdown led to tSC abnormalities, decreased tSC numbers, and more denervated endplates compared to controls. Our data suggest that hypothalamic Sirt1 functions to protect NMJs in skeletal muscle from age-related changes via sympathetic innervation.

Original languageEnglish
Article numbere12776
JournalAging Cell
Issue number4
Publication statusPublished - 2018 Aug
Externally publishedYes


  • NMJ
  • Sirt1
  • aging
  • neuromuscular junction
  • sirtuin
  • terminal Schwann cell

ASJC Scopus subject areas

  • Ageing
  • Cell Biology


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