Project description:Aging is accompanied by a loss of muscle mass and function, termed sarcopenia, causing numerous morbidities and economic burdens in human populations. Mechanisms implicated in age-related sarcopenia include inflammation, muscle stem cell depletion, mitochondrial dysfunction and loss of motor neurons, but whether there are key drivers of sarcopenia is not yet known. To gain deeper insights into age-related sarcopenia, we performed transcriptome profiling on lower limb muscle biopsies from 72 young, old and sarcopenic subjects using bulk RNA-seq (N = 72) and single-nuclei RNA-seq (N = 17). Using this combined approach, we discovered novel changes in gene expression that occur with age and sarcopenia in multiple cell types comprising mature skeletal muscle. Notably, we found increased expression of the genes MYH8 and PDK4, and decreased expression of the gene IGFN1, in old muscle. We also identified a small population of nuclei that express CDKN1A, present only in aged samples, consistent with P21CIP1 senescence in this subpopulation. Our findings identify unique cellular sub-populations populations in aged and sarcopenic skeletal muscle, which will facilitate the development of new therapeutic strategies to combat age-related sarcopenia.
Project description:a genomic profile of aged rat sceletal muscle with diffrent degrees of sensorimotor disturbances. Keywords: age skeletal muscle sensorimotor disturbances
Project description:Sarcopenia is the age-induced, progressive loss of skeletal muscle mass and function, which is accompanied by reduced muscle performance. Individuals with sarcopenia often become bedridden or dependent on a wheelchair, leading to decreased quality of life. In this study, to better understand changes in skeletal muscle during sarcopenia, we performed a microarray analysis of skeletal muscle in young (13-week-old) and aged (26-month-old) mice. The microarray data shows that expression of the enzymes related to glucose and polyamine metabolism were decreased in aged mice compared with young mice.
Project description:Expression profiles of mouse skeletal muscle tissues, mouse skeletal muscle from Aged animals with high fat diet and chemical treatment
Project description:Aged skeletal muscle is markedly affected by fatty muscle infiltration and strategies to reduce the occurrence of adipocytes within skeletal muscle, the intramuscular adipose tissue (IMAT), are urgently needed. Fibroblast growth factor-2 (FGF-2) is a critical growth factor for muscle tissue. Here, we show that FGF-2 not only stimulates muscle growth, but also promotes intramuscular adipogenesis. Using multiple screening assays for upstream and downstream signaling of microRNA (miR)-29a we located the secreted protein and adipogenic inhibitor SPARC to an FGF-2 signaling pathway that is conserved between skeletal muscle cells from mice and humans and that is activated in skeletal muscle from aged mice. FGF-2 induces the miR-29a/SPARC axis through transcriptional activation of FRA-1 which binds and activates an evolutionary conserved AP-1 site element proximal in the miR-29a promoter. Genetic deletions in muscle cells and AAV-mediated overexpression of FGF-2 or SPARC in mouse skeletal muscle revealed that this axis regulates differentiation of fibro/adipogenic progenitors in vitro and intramuscular fat formation in vivo. Thus, our data highlight an ambivalent role of FGF-2 for adult skeletal muscle and reveal a novel pathway to combat fat accumulation in aged skeletal muscle.
Project description:Heterochronic blood exchange (HBE) has demonstrated that circulating factors restore youthful features to aged tissues. However, the systemic mediators of those rejuvenating effects remain poorly defined. We show that the beneficial effect of young blood on aged muscle regeneration was diminished when serum was depleted of extracellular vesicles (EVs). Whereas EVs from young animals rejuvenate aged cell bioenergetics and skeletal muscle regeneration, aging shifts EV subpopulation heterogeneity and compromises downstream benefits on recipient cells. Machine learning classifiers revealed that aging shifts the nucleic acid, but not protein, fingerprint of circulating EVs. Alterations in sub-population heterogeneity were accompanied by declines in transcript levels of the pro-longevity protein, α-Klotho, and injection of EVs improved muscle regeneration in a Klotho mRNA-dependent manner. These studies demonstrate that EVs play a key role in the rejuvenating effects of HBE and that Klotho transcripts within EVs phenocopy the effects of young serum on aged skeletal muscle.
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 this experiment include 2 samples and 6 replicates
Project description:Syncytial skeletal muscle cells contain hundreds of nuclei in a shared cytoplasm. Using single nucleus RNA-sequencing (snRNAseq) of isolated nuclei from muscle fibers, we investigated nuclear heterogeneity and transcriptional dynamics in uninjured and regenerating muscle.