Profiling muscle from aged rat model for sarcopenia
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE38077 | GEO | 2013/03/22
SECONDARY ACCESSION(S): PRJNA167190
REPOSITORIES: GEO
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Project description:This program aims at identifying a muscle gene signature associated with aging in rat sarcopenia model The profiling data was analyzed by identifying genes that were up- and down-regulated at selected p value and fold change in the muscle of aged rats compared to the young controls.
2013-03-22 | E-GEOD-38077 | biostudies-arrayexpress
Project description:Aims: Sarcopenia is the degenerative loss of skeletal muscle mass and function at high age, which affects 5-13% of people aged 60-70 years. Although a number of factors have been linked to sarcopenia, it remains unclear what determines its emergence in some but not all individuals and there are no medical treatments available. Mice and rats are widely used as model organisms to identify factors predisposing to sarcopenia, but the extent to which age-related molecular changes in wild-type mice and rats recapitulate those occurring in humans is not known. The aim of this project was to define a conserved set of regulators of aging-related reduction in muscle function that could be targeted by future therapies. Methods: We comparatively analyzed phenotypic parameters as well as the transcriptomes of the Gastrocnemius muscle from mice, rats and humans of a wide range of ages. We further inferred computationally the transcription regulators that likely underlie the molecular changes associated with aging-related loss in muscle functionality. Results: The analysis showed that the biological age of rodents that muscle mass is a better indicator of muscle functionality than the chronological age. Investigating the molecular changes associated with the aging-related loss of muscle mass, we discovered changes in gene expression that are shared between the studied species at the level of molecular pathways rather than at the level of individual genes. Beyond the known involvement of inflammation and mitochondrial function in aging, we found that the transcription regulators SPIB, ESRRB and YY1/YY2 consistently underlie aging-related molecular changes across the studied species. Conclusions: Rodents recapitulate well the molecular changes observed in human sarcopenia, but the conservation is stronger at the molecular pathway level than at the level of individual genes. Phenotypic parameters such as the muscle mass should be taken into account in stratifying samples for analyzing aging-related processes, as the chronological age is a poorer indicator of organ functionality. The shared regulators of aging-related muscle loss that we identified here can be studied further in rodent models of sarcopenia toward defining new targets for therapy in humans.
2021-01-30 | GSE145480 | GEO
Project description:This program aims at identifying a skin gene signature associated with inflammation pain in rat CGN model
2013-03-22 | GSE38072 | GEO
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.
2021-06-26 | E-MTAB-10583 | biostudies-arrayexpress
Project description:Molecular mechanisms underlying sarcopenia, the age-related loss of skeletal muscle mass and function, remain unclear. To identify molecular changes that correlated best with sarcopenia and might contribute to its pathogenesis, we determined global gene expression profiles in muscles of rats aged 6, 12, 18, 21, 24, and 27 months. These rats exhibit sarcopenia beginning at 21 months. Correlation of the gene expression versus muscle mass or age changes, and functional annotation analysis identified gene signatures of sarcopenia distinct from gene signatures of aging. Specifically, mitochondrial energy metabolism (e.g., tricarboxylic acid cycle and oxidative phosphorylation) pathway genes were the most downregulated and most significantly correlated with sarcopenia. Also, perturbed were genes/pathways associated with neuromuscular junction patency (providing molecular evidence of sarcopenia-related functional denervation and neuromuscular junction remodeling), protein degradation, and inflammation. Proteomic analysis of samples at 6, 18, and 27 months confirmed the depletion of mitochondrial energy metabolism proteins and neuromuscular junction proteins. Together, these findings suggest that therapeutic approaches that simultaneously stimulate mitochondrogenesis and reduce muscle proteolysis and inflammation have potential for treating sarcopenia.
2018-08-21 | GSE118825 | GEO
Project description:Skeletal muscle aging results in a gradual loss of skeletal muscle mass, skeletal muscle function and decreased regenerative capacity, which can lead to sarcopenia and increased mortality. While the mechanisms underlying sarcopenia remain unclear, the skeletal muscle stem cell, or satellite cell, is required for muscle regeneration. Therefore, identification of signaling pathways affecting satellite cell function during aging may provide insights into therapeutic targets for combating sarcopenia. Here, we show that a cell-autonomous loss in self-renewal occurs via novel alterations in FGF and p38αβ MAPK signaling in old satellite cells. We further demonstrate that pharmacological manipulation of these pathways can ameliorate age-associated self-renewal defects. Thus, our data highlight an age-associated deregulation of a satellite cell homeostatic network and reveals potential therapeutic opportunities for the treatment of progressive muscle wasting. Satellite cells were isolated from young (3-6mo) and aged (20-25mo) adult mice; individual date files represent 2 independent pools of RNA from 4-8 mice at each timepoint.
2013-09-01 | E-GEOD-47104 | biostudies-arrayexpress
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.
2022-03-31 | GSE167186 | GEO
Project description:Skeletal muscle aging is characterized by a progressive decline in muscle mass and function, which is referred to as sarcopenia. However, the molecular mechanisms implicated in sarcopenia remain unclear. In this dataset, we include the expression data obtained from gastrocnemius muscle of young, mature adult and old C57BL6 male mice.
2021-08-18 | GSE136266 | GEO
Project description:Mitochondrial fusion and fission proteins regulate mitochondrial quality control and mitochondrial metabolism. In turn, mitochondrial dysfunction is associated with aging, although its causes are still under debate. Here, we show that aging is characterized by a progressive reduction of Mitofusin 2 (Mfn2) in mouse skeletal muscle and that skeletal muscle Mfn2 ablation in mice generates a gene signature linked to aging. Furthermore, muscle Mfn2-deficient mice show unhealthy aging characterized by altered metabolic homeostasis and sarcopenia. Mfn2 deficiency impairs mitochondrial quality control, which contributes to an exacerbated age-related mitochondrial dysfunction. Surprisingly, aging-induced Mfn2 deficiency triggers a ROS-dependent retrograde signaling pathway through induction of HIF1 transcription factor and BNIP3. This pathway ameliorates mitochondrial autophagy and minimizes mitochondrial damage. Our findings reveal that repression of Mfn2 in skeletal muscle during aging is determinant for the loss of mitochondrial quality, contributing to age-associated metabolic alterations and loss of muscle fitness. Quadriceps muscle from four mice per genotype were used (Control young (6 month-old), Mfn2KO young (6-month-old), control old (22-month-old) and Mfn2KO old (22-month-old)
2016-08-08 | E-GEOD-71501 | biostudies-arrayexpress
Project description:Abstract Background: The prevalence of sarcopenia is increasing and effective interventions are required to prevent or reverse age-related muscle loss. However it is often challenging expensive and time-consuming to develop and test the effectiveness of such interventions. Furthermore translational animal models that adequately mimic underlying physiological pathways are scarce. Strong predictors for the incidence of sarcopenia include a sedentary life-style and malnutrition. Therefore our objective was to investigate the translational value of three potential mouse models for sarcopenia namely partial immobilized caloric restricted (CR) and a combination (immobilized & CR) model. Methods: C57BL/6J mice were calorically restricted (-40%) and/or one hindleg was immobilized for two weeks to induce loss of muscle mass and function. Muscle mass function and diameter and distribution of slow (type 1) and fast ( type 2) myofibers were compared to those of young control (4 months) and old reference mice (21 months). Transcriptome analysis of quadriceps muscle was performed to identify underlying pathways and were compared with those being expressed in aged human vastus lateralis muscle-biopsies using a meta-analysis of five different human studies. Results: Caloric restriction induced overall loss of lean body mass (-15% p<0.001) whereas immobilization decreased muscle strength (-28% p<0.001) and muscle mass of hindleg muscles specifically (on average -25% p<0.001). The proportion of slow myofibers increased with aging in mice (+5% p<0.05) and this was not recapitulated by the CR and/or immobilization models. The diameter of fast myofibers decreased with aging (-7% p<0.05) and this was mimicked by all models. Transcriptome analysis revealed that the combination of CR and immobilization recapitulated more pathways characteristic for human muscle-aging (73%) than naturally aged (21 months old) mice (45%). These pathways included critical pathways relevant for protein synthesis/ breakdown (mitochondrial) metabolism neurology and the vascular system. Conclusions: The combination model exhibits loss of both muscle mass (due to CR) and function (due to immobilization) and has a remarkable similarity with pathways underlying human sarcopenia. Our results demonstrate that naturally aging up to 21 months in mice only partially recapitulates the human pathology with fewer overlapping pathways than the combination model. These findings underline that external factors such as sedentary behavior and malnutrition are key elements of a translational mouse model and favor the combination model as a rapid model for testing the treatments against sarcopenia.
2022-12-16 | GSE213148 | GEO