Improving translatability of spinal cord injury research by including age as a demographic variable

Frontiers in Cellular Neuroscience, 2022 · DOI: 10.3389/fncel.2022.1017153 · Published: November 17, 2022

Simple Explanation

Pre-clinical and clinical studies on spinal cord injury (SCI) have different designs, especially in the characteristics of the people or animals studied. Clinical trials often include people of different ages and both sexes, while animal studies mostly use young adult rodents, usually only females. It's difficult to design clinical trials that test how age affects treatment outcomes because it's hard to include enough people of different ages. But recent animal studies suggest that age is an important factor to consider before testing treatments on humans. Some treatments have shown different levels of effectiveness depending on the age of the animals, and age can affect how the body responds to SCI. These differences can make trial results harder to understand and may lead to worse outcomes for certain patients.

Study Duration

Not specified

Participants

Pre-clinical SCI models predominately utilize young adult rodents

Evidence Level

Review

Key Findings

1
Older age at the time of SCI is associated with worse functional outcomes, even when injury severity, anatomical location, and injury type are controlled across age groups in rats and mice.
2
Older age at the time of injury is associated with increased recruitment of macrophages into the lesion in both rats and mice.
3
Mitochondria from older mice produce more ROS and less ATP for cellular energy compared to younger mice.

Research Summary

Age as a biological variable affects SCI injury and recovery processes as well as responses to treatments in often unpredictable ways. Mechanisms underlying a diminished functional recovery after SCI at older ages have implicated a reduced capacity for axon growth and regeneration in both non-intervened and intervened conditions, as well as more severe secondary injury cascades. Most intriguingly, treating older mice after SCI with several antioxidant-based strategies has resulted in outcomes which would either be predictive based on the underlying biology, or completely counterintuitive to the logical hypothesis.

Practical Implications

Pre-clinical models

Therapeutic treatments should be examined across the spectrum of age in pre-clinical models prior to investing time and resources into human investigations.

Clinical trial design

Results from animal testing will re-enforce clinical trial design by providing insights into which age ranges are most susceptible to experiencing a benefit from treatment.

Basic science

Treatment efforts deemed marginal or insignificant in young rodent models may potentially exert a more significant effect at older ages, and therefore can implicate a re-evaluation of treatment efforts in older animal models.

Study Limitations

1
It is impossible to test the same cohort of mice at two different ages at the same time, resulting in the use of different cohorts to represent differences in age.
2
Mice and rats gain weight with age, which can confound the interpretation or analysis of results.
3
Baseline differences in functional outcomes, such as sensory thresholds and measures of forelimb strength, are reported to decline with older ages in uninjured rodents.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury