Age-related gene expression signatures from limb skeletal muscles and the diaphragm in mice and rats reveal common and species-specific changes

作者：Tea Shavlakadze, Kun Xiong, Shawn Mishra, Corissa McEwen, Abhilash Gadi, Matthew Wakai, H. A. Salmon, Michael J. Stec, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Yu Bai, David J. Glass · 发表于：Skeletal Muscle · 年份：2023 · DOI：10.1186/s13395-023-00321-3 · 被引用次数：42 · 研究领域：Muscle Physiology and Disorders、Nutrition and Health in Aging、GDF15 and Related Biomarkers

BACKGROUND: As a result of aging, skeletal muscle undergoes atrophy and a decrease in function. This age-related skeletal muscle weakness is known as "sarcopenia". Sarcopenia is part of the frailty observed in humans. In order to discover treatments for sarcopenia, it is necessary to determine appropriate preclinical models and the genes and signaling pathways that change with age in these models. METHODS AND RESULTS: To understand the changes in gene expression that occur as a result of aging in skeletal muscles, we generated a multi-time-point gene expression signature throughout the lifespan of mice and rats, as these are the most commonly used species in preclinical research and intervention testing. Gastrocnemius, tibialis anterior, soleus, and diaphragm muscles from male and female C57Bl/6J mice and male Sprague Dawley rats were analyzed at ages 6, 12, 18, 21, 24, and 27 months, plus an additional 9-month group was used for rats. More age-related genes were identified in rat skeletal muscles compared with mice; this was consistent with the finding that rat muscles undergo more robust age-related decline in mass. In both species, pathways associated with innate immunity and inflammation linearly increased with age. Pathways linked with extracellular matrix remodeling were also universally downregulated. Interestingly, late downregulated pathways were exclusively found in the rat limb muscles and these were linked to metabolism and mitochondrial respiration; this was not ...