Abstract
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.
Highlights
Spinal Cord Injury (SCI) is the second most common cause of paralysis and results in varying degrees of motor and sensory dysfunction over the lifetime of the patient
We observed a significant increase in the expression of TIM23 in cortical neurons with age, which may indicate a compensatory mechanism to help promote mitochondrial function and increase survival
Mitochondria are vital to the growth and regeneration of axons after injury, and this capability decreases in the aging central nervous system (CNS)
Summary
Spinal Cord Injury (SCI) is the second most common cause of paralysis and results in varying degrees of motor and sensory dysfunction over the lifetime of the patient. As a result of the increasing incidence of SCI in middle-aged and aging populations and the fact that people with SCI are living longer, the average age of people who reported paralysis due to an SCI is approximately 48 years old [4]. In contrast to the human SCI population, the majority of preclinical research is performed in young adult rodents (2–4 months), and less than 0.35% of experimental rodents used are 12 months or older (representing 40 years of age in humans) [5]. This is likely to be a significant impediment to translating preclinical research into viable clinical therapies
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