Sexual Dimorphism in Mouse Age-Related Motor Impairments

Purpose: Clinical measures such as frailty, disability, and strength loss are correlated with decreased survival and are more prevalent in women, yet men have a higher mortality risk at all ages. This contradictory sexual dimorphism in mortality versus morbidity is not fully understood. Furthermore, many pre-clinical studies using rodents have combined sexes or tested only males which limits the possible inferences regarding sex-dependent changes in function across the lifespan as well as inferences relating to interventions. Therefore, the purpose of this study was to examine murine sexual dimorphism in age-related motor function decline. Our hypothesis was that motor impairments would increase with age, and that these deficiencies would be exacerbated in females. Methods: Male and female C57BL/6J mice were tested at 5, 10, and 20 months of age. Animals underwent a battery of behavioral tests measuring difference aspects of motor function, including tests measuring coordinated running and motor learning (rotorod), strength (wire suspension), and balance (bridge walking). Resulting dependent measures were analyzed using two-way analyses of variance with Age and Sex as between-groups factors and two-way repeated measures analyses of variance with Session as the within group factor. Results: Rotorod performance (learning and maximum) declined with age in both sexes, however declines were smaller for females at 10 and 20 months compared to the males. Latency to fall from the wire was significantly shorter in adult and old males compared to their young counterpart, while there was no significant differences in the females. Bridge walking performance declined in both males and females, but there was a larger decline in the males. Furthermore, age-related decline in balance was observed in the females only on the most difficult bridge, while age-related declines were apparent on all the bridges for the males. Conclusions: These data support that age-related decline leads to measurable changes in mouse motor function. However these deficits occur primarily in the males whereas females displayed fewer and smaller declines in motor function. This suggests that combining sexes or testing only a single sex could lead to limited results. Interestingly, women are typically more sensitive to age-related functional decline, while female mice in our study were less affected by age-related decline. In conclusion, this study highlights the importance of including both sexes in rodent pre-clinical research.