Brain Neurons during Physiological Aging: Morphological Features, Autophagic and Mitochondrial Contribution

Int J Mol Sci. 2022 Sep 14;23(18):10695. doi: 10.3390/ijms231810695.

Abstract

Accumulating data suggest that the brain undergoes various changes during aging. Among them are loss of both white and gray matter, neurons and synapses degeneration, as well as oxidative, inflammatory, and biochemical changes. The above-mentioned age-related features are closely related to autophagy and mitochondria. Therefore, we aimed to reveal the most peculiar morphological features of brain nervous tissue and to characterize the expression of autophagy and mitochondrial immunohistochemical biomarkers in neurons of different human brain zones during aging. Counting the number of neurons as well as Microtubule-associated proteins 1A/1B light chain 3B (LC3B), Heat shock protein 70 (HSP70), Lysosome-associated membrane protein type 2A (LAMP2A), Alpha subunit of ATP synthase (ATP5A), and Parkinson disease protein 7 (DJ1) immunohistochemical staining were performed on FFPE samples of human prefrontal cortex, corpus striatum, and hippocampus obtained from autopsy. Statistical analysis revealed a loss of neurons in the studied elderly group in comparison to the young group. When the expression of macroautophagy (LC3B), chaperon-mediated autophagy (HSP70, LAMP2A), and mitochondrial respiratory chain complex V (ATP5A) markers for the young and elderly groups were compared, the latter was found to have a significantly higher rate of optical density, whilst there was no significance in DJ1 expression. These findings, while preliminary, suggest that both autophagy and mitochondria are involved in neuronal maintenance during aging and could indicate their potential role in adaptive mechanisms that occur in aging.

Keywords: aging; chaperon-mediated autophagy; macroautophagy; mitochondria; neurons.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Aged
  • Autophagy*
  • Biomarkers / metabolism
  • Brain / metabolism
  • HSP70 Heat-Shock Proteins / metabolism
  • Humans
  • Lysosomal Membrane Proteins / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Mitochondria* / metabolism
  • Neurons / metabolism

Substances

  • Biomarkers
  • HSP70 Heat-Shock Proteins
  • Lysosomal Membrane Proteins
  • Microtubule-Associated Proteins
  • Adenosine Triphosphate