Persistent Skeletal Muscle Overexpression of Inflammatory Lipid Mediators after Disuse Corresponds to Impaired Skeletal Muscle Recovery in Aged Mice

Aging is associated with impaired recovery of muscle mass and function after a period of disuse, often leading to an increased risk of falls and fractures. The exact mechanisms behind impaired recovery due to aging after disuse are not fully understood. Membrane-derived lipids mediators (LM) in muscle orchestrate inflammatory actions that are critical for restoration of muscle following injury. We tested the hypothesis that muscle LM associated with inflammation would be dysregulated in adult vs older mice during a time course of recovery following disuse atrophy. Therefore, we designed a study in which adult (3-6m/o) and old (23-26m/o) male mice underwent 14 days of hindlimb unloading followed by 2, 4, or 7 days of reloading. The gastrocnemius muscle was collected at each timepoint and between age groups and processed for lipidomic analysis of the eicosanoids. Gastrocnemius muscle mass showed impaired recovery after HU in the old group when compared to adult, at 4 (P=0.0420) and 7 days reload (P=0.0092). We also observed that muscle LM’s associated with acute inflammation (arachidonic acid, prostaglandins, leukotrienes) were significantly overexpressed in old mice during recovery after disuse. Importantly, several of these lipids corresponded with impaired muscle recovery. PGE2 and PGF2a levels showed a correlation (P=0.03 and P=0.02, respectively) with gastrocnemius mass at the 4 days reload. We conclude that recovery from disuse in aged mice are characterized with the upregulation of pro-inflammatory lipids in muscle and this may be related to poor muscle regrowth. Future studies will be considered to determine the role and cell source of these pro-inflammatory LM during muscle recovery in aged mice. Funding was provided by NIH: R01AG076075 awarded to M.J.D. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.