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Molecular changes associated with spinal cord aging.

Katarzyna M Piekarz1,2, Shylesh Bhaskaran2, Kavithalakshmi Sataranatarajan2

  • 1Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73117, USA.

Geroscience
|March 8, 2020
PubMed
Summary
This summary is machine-generated.

Aging causes significant spinal cord changes, including alpha motor neuron (α-MN) loss, inflammation, and increased vascular permeability, contributing to muscle weakness in the elderly.

Keywords:
Age-related neuronal lossAgingMMPsMotor neuronsSpinal cord

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Area of Science:

  • Neuroscience
  • Aging Research
  • Muscle Physiology

Background:

  • Sarcopenia, characterized by age-related muscle weakness and mass loss, is a major health concern in the elderly.
  • Alpha motor neurons (α-MNs) are critical for muscle innervation and function, and their decline is implicated in sarcopenia.

Purpose of the Study:

  • To investigate age-related changes in the spinal cord that lead to muscle denervation and subsequent skeletal muscle degeneration.
  • To identify molecular and cellular mechanisms underlying spinal cord aging and α-MN loss.

Main Methods:

  • Comparative analysis of spinal cord tissue from young and aged wildtype mice.
  • Assessment of α-MN counts, myelin integrity, inflammation markers (astrocyte/microglia activation, sICAM-1), and neuronal viability markers (N-acetyl-aspartate, cleaved caspase-3).
  • RNA sequencing (RNA-seq) to analyze gene expression changes, focusing on extracellular matrix (ECM) components and MMP-12.
  • Evaluation of blood-spinal cord barrier (BSCB) permeability.

Main Results:

  • A significant decrease (41% by 27 months) in spinal cord α-MNs was observed in aged mice.
  • Evidence of age-related myelin loss, mild inflammation (astrocyte/microglia activation), and increased sICAM-1.
  • Reduced N-acetyl-aspartate and increased cleaved caspase-3 indicate compromised neuronal viability and apoptosis.
  • RNA-seq revealed altered expression of ECM genes and a substantial (172-fold) increase in MMP-12.
  • Increased BSCB permeability was noted in aged mice.

Conclusions:

  • The aging spinal cord undergoes substantial changes, including progressive α-MN loss, contributing to sarcopenia.
  • These changes involve low-grade inflammation, apoptosis, alterations in ECM composition, myelin degradation, and increased vascular permeability.
  • Spinal cord aging is a critical factor in age-related muscle dysfunction.