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Updated: Jun 14, 2025

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Functional and Structural Changes in Diaphragm Neuromuscular Junctions in Early Aging.

Andrei N Tsentsevitsky1, Guzel V Sibgatullina1, Yulia G Odoshivkina1,2

  • 1Kazan Institute of Biochemistry and Biophysics, Federal Research Center "Kazan Scientific Center of RAS", 2/31 Lobachevsky Street, P.O. Box 30, 420111 Kazan, Russia.

International Journal of Molecular Sciences
|August 29, 2024
PubMed
Summary

Middle-aged mice show enhanced neuromuscular communication and diaphragm function, suggesting improved diaphragm activity during early aging. These findings reveal key changes in the neuromuscular junction before old age.

Keywords:
acetylcholineagingcontractiondiaphragmend-plateneuromuscular junctionneurotransmitter releaserespirationsynapsinsynaptic vesicle

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Area of Science:

  • Physiology
  • Neuroscience
  • Aging Research

Background:

  • Diaphragm aging leads to respiratory issues, with neuromuscular junction (NMJ) dysfunction implicated in elderly individuals.
  • While diaphragm NMJ changes are known in old age, alterations in middle age remain poorly understood.

Purpose of the Study:

  • To investigate diaphragm neuromuscular junction structural and functional changes in middle-aged mice compared to young adults.
  • To correlate NMJ alterations with diaphragm contractile function and respiratory patterns in early aging.

Main Methods:

  • Comparison of diaphragm muscles from young adult (3 months) and middle-aged (12 months) BALB/c mice.
  • Utilized microelectrode recordings, immunofluorescent staining, electron microscopy, myography, and whole-body plethysmography.

Main Results:

  • Presynaptic changes included increased action potential velocity and neurotransmitter release, but decreased synapsin 1 and vesicle clustering.
  • Postsynaptic alterations involved reduced nicotinic acetylcholine receptor currents and distribution area.
  • NMJ changes correlated with enhanced diaphragm contractility and altered respiration patterns (increased peak inspiratory flow, elevated tidal volume tendency).

Conclusions:

  • Early aging in mice enhances neuromuscular communication via presynaptic mechanisms in the diaphragm.
  • Improved diaphragm contractile responses accompany these NMJ adaptations in middle age.
  • These findings suggest increased diaphragm activity in middle-aged mice, potentially as a compensatory mechanism before age-related decline.