Project description:To gain new insights into molecular changes in skeletal muscle aging and disease with a special focus on differential alternative splicing and senescence, we performed RNA-seq on tibialis muscles from 15 months old (adult, a) and 27 months old (old, o) rats. Whole (w) muscle samples were prepared for both age groups (w/a and w/o). Additionally, for both age groups, muscle fibers were isolated. For adult rats, this resulted in one group (f/a). For old rats, fibers were subjected to Laser capture microdissection guided by expression of aging markers Tmem158 and Cdkn1a, giving rise to two groups, aging marker-positive fibers (f/o+) and aging marker-negative fibers (f/o-). The entire experiment comprises 5 groups (w/a, w/o, f/a, f/o+, f/o-), with 5 animals per group, ie. 25 samples total.
Project description:To gain new insights into molecular changes in skeletal muscle aging and disease with a special focus on differential alternative splicing and senescence, we performed RNA-seq on rat gastrocnemius muscles of animals aged 6, 12, 18, 21, 24 and 27 months, using a rat sarcopenia model we had previously established.
Project description:To investigate the roles of ATF4 in skeletal muscle aging we generated muscle-specific ATF4 knockout (ATF4 mKO) mice. We then performed gene expression profiling analysis using data obtained from RNA-seq of tibialis anterior muscles at 6-months and 22-months of age.
Project description:Mouse tibialis anterior muscles were electroporated with Nr2f6-myc plasmid or pCMV6 empty vector in the contralateral leg. After 9 days, muscles were collected, and the RNA extracted and processed for microarray analysis.
Project description:Skeletal muscle atrophy is one of the critical issues which elderly people face. The precise mechanism underlying muscle atrophy during aging is not fully understood. In order to identify miRNA whose expression is changed in age-associated muscle atrophy, we performed miRNA expression profiling of skeletal muscles in young and aged rats. Microarray analysis revealed differential miRNA expression in EDL and soleus muscles of aged rats compared with those of young rats. We next investigated whether the age-associated changes of miRNA expression observed in rats were recapitulated in mice and found that the expression level of miR-206 in EDL muscle and that of miR-196a in EDL and soleus muscles were respectively higher and lower in aged rodents than in young rodents. In mouse C2C12 myoblasts and myotubes, introduction of miR-196a decreased the protein level of Forkhead-box transcription factor Foxo1, a known target of miR-196a, indicating that miR-196a may regulate Foxo1 expression also in skeletal muscles. Furthermore, miR-196a overexpression exacerbated cell death caused by an exposure to hydrogen peroxide. Lastly, we demonstrated that expression of Foxo1 was elevated in EDL and soleus muscles of aged mice compared with those of young mice. These results suggest that miRNAs are involved in skeletal muscle atrophy during aging and that decreased miR-196a expression may protect skeletal muscle cells from oxidative stress in part through induction of Foxo1.
Project description:To investigate the role of the circadian clock gene Bmal1 in skeletal muscle, we compared the circadian transcriptomes of fast tibialis anterior (TA) and slow soleus (SOL) skeletal muscles from muscle-specific Bmal1 KO (mKO) and their control Cre- littermates (Ctrl). Keyword: Circadian Transcriptome, time course
Project description:To investigate the role of the circadian clock gene Bmal1 in skeletal muscle, we compared the circadian transcriptomes of fast tibialis anterior (TA) and slow soleus (SOL) skeletal muscles from muscle-specific Bmal1 KO (mKO) and their control Cre- littermates (Ctrl). Keyword: Circadian Transcriptome, time course 72 samples were analyzed, comprised of 4 experimental groups (Ctrl SOL, mKO SOL, Ctrl TA, mKO TA), with 3 biological replicates for each time point sampled every 4 hours for 24 hours. SOL and TA muscles were collected from the same animals, as indicated by Source Animal ID data column
Project description:Male Fischer 344 rats aged 4 months (young, n=10), 14 months (mid-aged, n=10), and 24 months (aged, n=10) were trained sequentially on two tasks: Morris Spatial Water Maze (SWM) and Object Memory Task (OMT). The training/testing sequence lasted 7 d, and hippocampal tissue was collected 24 hr later. Training and testing occured on each day except for days 2 and 3 of the 7 d sequence. (01/10/05: Series was updated to correct mislabeling of all sample signal values within the Young Treatment Group)