Project description:Aging in multicellular organisms is characterized by gradual decline of organ functionality. To study the aging process, we used mRNA sequencing (mRNA-seq) to identify gene expression changes during aging in healthy mice. Skeletal muscle tissues of wild-type mice at 3 months and 24 months of age were collected and mRNA-seq libraries were prepared and sequenced on a HiSeq2500 by single-end sequencing with 100 bp read length. Analysis of the expression profiles of aged skeletal muscle tissues showed decreased mRNA levels of genes function in lipid metabolism, peptidase activity and response to stimulus.
Project description:Utilizing glycerol intramuscular injections in M. musculus provide a models of skeletal muscle damage followed by skeletal muscle regeneration. In particular, glycerol-induced muscle injury triggers accute activation of skeletal muscle stem cells, called satellite cells. However, aging dramatically impairs the regenerative capacity of satellite cells. We characterized genome-wide expression profiles of young and old satellite cells in the non-proliferative and activated state, freshly isolated to non-injured or damaged muscles, respectively. Our goal was to uncover new regulatory signaling specific to satellite cells entry into the activation and myogenic program that are affected with age. Satellite cells were isolated in either quiescent / non-proliferative or activated state from uninjured or 3 days after glycerol-induced injury of tibialis anterior, gastrocnemius and quadriceps, respectively. Young (2-4 months old) and old (20-24 months old) wildtype C57BL/6J male were used, with five to six biological replicates per group.
Project description:We generated skeletal muscle-specific knockout mice lacking the transcription factor Yin Yang 1 (YY1) and analyzed expression patterns in the skeletal muscle these mice. We used microarrays to detail the global programme of gene expression regulated by YY1. Wild type or knockout mice at 6 months were sacrificed and the soleus was isolated for RNA extraction.
Project description:We report comprehensive miRNA expression profiles by miRNA-seq analysis in tibialis anterior muscle and serum of a disuse-induced atrophy model, compared with young (6 months) and old (24 months) mice.
Project description:Our laboratory wanted to define the transcription profile of aged skeletal muscle. For this reason, we performed a triplicate microarray study on young (3 weeks) and aged (24 months) gatrocnemius muscle from wild-type C57B16 Mice Keywords: other
Project description:Maintaining skeletal muscle mass is of high importance as muscle atrophy like during sarcopenia or cachexia lead to a decrease in independence and a higher risk of morbidity and mortality. A leading compound in the treatment against ageing and cancer is rapamycin, an inhibitor of mechanistic target of rapamycin complex 1 (mTORC1). Whether the treatment with mTORC1 inhibitors would work at a cost of losing muscle mass is unclear, as most studies have been focusing on the role of mTORC1 specifically during hypertrophy. In order to answer this question we developed an inducible muscle specific knockout mouse model in which raptor can be ablated during adulthood to eliminate mTORC1 activity. We analysed the muscles after different time points and found that after 3 months the mice showed a fiber shift towards slower fiber types, a loss in oxidative capacity but only very few myopathic features. After 5 months the myopathic features became more apparent, however it did not largely affect the ex vivo muscle force. Surprisingly despite the myopathy we did not see a significant loss of muscle mass even after 5 months, that we hypothesised based on mTORC1s central role in protein synthesis. We assume that the myopathy after long-term mTORC1 inactivation is mostly a result of secondary effects through the loss of mitochondria, alterations in metabolism and in cytoskeletal components. In conclusion, during skeletal muscle maintenance mTORC1 is more essential for metabolic processes than it is for maintaining basal muscle mass.Maintaining skeletal muscle mass is of high importance as muscle atrophy like during sarcopenia or cachexia lead to a decrease in independence and a higher risk of morbidity and mortality. A leading compound in the treatment against ageing and cancer is rapamycin, an inhibitor of mechanistic target of rapamycin complex 1 (mTORC1). Whether the treatment with mTORC1 inhibitors would work at a cost of losing muscle mass is unclear, as most studies have been focusing on the role of mTORC1 specifically during hypertrophy. In order to answer this question we developed an inducible muscle specific knockout mouse model in which raptor can be ablated during adulthood to eliminate mTORC1 activity. We analysed the muscles after different time points and found that after 3 months the mice showed a fiber shift towards slower fiber types, a loss in oxidative capacity but only very few myopathic features. After 5 months the myopathic features became more apparent, however it did not largely affect the ex vivo muscle force. Surprisingly despite the myopathy we did not see a significant loss of muscle mass even after 5 months, that we hypothesised based on mTORC1s central role in protein synthesis. We assume that the myopathy after long-term mTORC1 inactivation is mostly a result of secondary effects through the loss of mitochondria, alterations in metabolism and in cytoskeletal components. In conclusion, during skeletal muscle maintenance mTORC1 is more essential for metabolic processes than it is for maintaining basal muscle mass.
Project description:Our study aimed to characterize sarcopenia in C57BL/6J mice using a clinically relevant definition and age range and investigate the underlying mechanisms leading to sarcopenia. Aged male C57BL/6J mice (23-32 months) were classified as non-sarcopenic (no deficit), probable sarcopenic (1 deficit), and sarcopenic (2-3 deficits) based on assessments of grip strength, muscle mass, and treadmill running time and using 2 standard deviations below the mean of the young (4-9 months) as cut-off points. A 9-22% prevalence of sarcopenia was identified in 23-26-month-old mice. Age-related declines in muscle function were more severe than in muscle mass and outcomes of all three assessments were positively correlated in aged mice. As sarcopenia progressed, there were decreases in specific force as well as fiber size and number of IIB skeletal muscle fibers. Mitochondrial biogenesis, oxidative capacity, and AMPK-autophagy signaling decreased significantly while no increase in atrogenes was detected. Our study is the first to characterize sarcopenia in C57BL/6J mice using a clinically relevant definition and highlights the different trajectories of age-related declines in muscle mass and function. These critical insights into the molecular changes associated with sarcopenia progression will facilitate future development of therapeutic interventions.
Project description:TMT sixplex Isobaric Mass Tagging (TAM) analysis was carried out in the CBMSO Protein Chemistry Facility (ProteoRed, PRB3-ISCIII and UAM University, Spain. Chronic skeletal muscle mitochondria dyshomeostasis drives tubular aggregate formation.