Age-Dependent Decline in Neuron Growth Potential and Mitochondria Functions in Cortical Neurons

Cells. 2021 Jun 29;10(7):1625. doi: 10.3390/cells10071625.


The age of incidence of spinal cord injury (SCI) and the average age of people living with SCI is continuously increasing. However, SCI is extensively modeled in young adult animals, hampering translation of research to clinical applications. While there has been significant progress in manipulating axon growth after injury, the impact of aging is still unknown. Mitochondria are essential to successful neurite and axon growth, while aging is associated with a decline in mitochondrial functions. Using isolation and culture of adult cortical neurons, we analyzed mitochondrial changes in 2-, 6-, 12- and 18-month-old mice. We observed reduced neurite growth in older neurons. Older neurons also showed dysfunctional respiration, reduced membrane potential, and altered mitochondrial membrane transport proteins; however, mitochondrial DNA (mtDNA) abundance and cellular ATP were increased. Taken together, these data suggest that dysfunctional mitochondria in older neurons may be associated with the age-dependent reduction in neurite growth. Both normal aging and traumatic injury are associated with mitochondrial dysfunction, posing a challenge for an aging SCI population as the two elements can combine to worsen injury outcomes. The results of this study highlight this as an area of great interest in CNS trauma.

Keywords: CNS Injury; aging; dysfunction; mitochondria; mitochondrial respiration; neurite growth.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Aging / pathology*
  • Animals
  • Cell Respiration
  • Cells, Cultured
  • Cerebral Cortex / pathology*
  • DNA Copy Number Variations / genetics
  • DNA, Mitochondrial / metabolism
  • Electron Transport
  • Intracellular Space / metabolism
  • Membrane Potential, Mitochondrial
  • Membrane Proteins / metabolism
  • Mice, Inbred C57BL
  • Mitochondria / metabolism*
  • Mitochondrial Membranes / metabolism
  • Neurites / metabolism
  • Neurons / metabolism*
  • Neurons / pathology*
  • Oxidative Phosphorylation


  • DNA, Mitochondrial
  • Membrane Proteins
  • Adenosine Triphosphate