Higher Susceptibility to Skeletal Muscle TA (Tibialis Anterior) Injury with Increased Inflammation in Aged Mice.

Abstract

BackgroundSkeletal muscle contributes to a major portion of normal human body weight and plays a key role for physiological functions including growth, development and a host of metabolic regulating roles. Therefore, skeletal muscle injury is a major concern, particularly in pediatric and older populations.ObjectiveTo evaluate the differences in skeletal muscle injury, we utilized male Wild type C57BL6 young (5‐month old; n=4), and mature‐aged (12‐month old; n=4) aging mouse models.MethodsWe utilized Barium Chloride injection to induce inflammatory damage to the tibialis anterior muscle (TA), and monitored early skeletal muscle changes during 72 hours. Immunohistochemistry and morphometric analysis was conducted to identify changes between saline treated vs. barium chloride treated TA muscle.ResultsH&E staining from injured TA muscle identified an area of damage of ~52% in the young compared to a significantly larger area of damage of ~78% in mature mice. We also performed histomorphometric analyses to identify additional morphological changes. We found changes consistent with an increased cross sectional area post injury along with increased inflammation in the injured TA muscle.ConclusionsThe barium chloride TA muscle injury model allows for evaluation of TA muscle injury as early as 72‐hour post injection. Barium chloride injured muscles show significantly increased inflammation compared with saline injected muscle. The mature‐aged 12‐month old mice demonstrated greater injured area and enhanced inflammatory response, suggesting that even in mature mice, there is an increased susceptibility to muscle damage. These findings might have previously unforeseen consequences for older adults reaching middle age.Support or Funding InformationNIH R01 DK119066 and William N. Saunders Endowment in geriatric pharmacotherapy to (SMT). MB was partially supported by NIH‐National Institutes of Aging PO1 AG039355 (M.B.), and R01AG056504 and R01 AG060341 (M.B.), and the George W. and Hazel M. Jay and Evanston Research Endowments (MB).