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

Aging Cell
Alison K Snyder-WarwickAlbina Jablonka-Shariff

Abstract

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 v...Continue Reading

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Citations

Aug 14, 2019·Muscle & Nerve·Bianca VannucciAlison K Snyder-Warwick
Dec 19, 2019·Brain : a Journal of Neurology·Virenkumar A Pandya, Rickie Patani
Dec 29, 2020·Frontiers in Aging Neuroscience·Zhengyuan BaoWing-Hoi Cheung
Dec 18, 2020·Frontiers in Molecular Neuroscience·Yomna Badawi, Hiroshi Nishimune
May 13, 2021·Brain Communications·Abrar AlhindiThomas H Gillingwater
Apr 6, 2021·Aging and Disease·Sandra Fuertes-Alvarez, Ander Izeta
Jan 7, 2022·Journal of Anatomy·Samuele NegroMichela Rigoni

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