Similar Datasets
Project description:To uncover new pathways that are important for skeletal muscle stem cell aging, we performed multiomics profiling, including transcriptomics, DNA methylomics, proteomics, and metabolomics on quiescent muscle stem cells from young and old mice. Our goals were to discover pathways that have been overlooked by isolated profiling approaches and to gain insight into which changes are causal, compensatory, correlational, and consequential. In our work, we found that glutathione metabolism is a key pathway of muscle stem cell aging that involves a compensatory feedback loop. Follow-up experiments showed that old muscle stem cells actually form a dichotomy between glutathione-high muscle stem cells and glutathione-low muscle stem cells. RNA-Seq showed that glutathione-high old muscle stem cells are able to synthesize adequate glutathione and thus compensate adequately for oxidative stress with increased glutathione turnover, while glutathione-low old muscle stem cells have failed to compensate for oxidative stress metabolically and instead show increased inflammatory signaling.
2023-03-20 | GSE152797 | GEO
Project description:To uncover new pathways that are important for skeletal muscle stem cell (MuSC) aging, we performed multiomics profiling, including transcriptomics, DNA methylomics, proteomics, and metabolomics on quiescent MuSCs from young and old mice. Our goals were to discover pathways that have been overlooked by isolated profiling approaches and to gain insight into which changes are causal, compensatory, correlational, and consequential. In our work, we found that glutathione metabolism is a key pathway of MuSC that involves a compensatory feedback loop. Follow-up experiments showed that old MuSCs actually form a dichotomy between glutathione-high MuSCs and glutathione-low MuSCs. RNA-Seq showed that glutathione-high old MuSCs are able to synthesize adequate glutathione and thus compensate adequately for oxidative stress with increased glutathione turnover, while glutathione-low old MuSCs have failed to compensate for oxidative stress metabolically and instead show increased inflammatory signaling.
2023-03-20 | GSE152796 | GEO
Project description:To uncover new pathways that are important for skeletal muscle stem cell aging, we performed multiomics profiling, including transcriptomics, DNA methylomics, proteomics, and metabolomics on quiescent muscle stem cells from young and old mice. Our goals were to discover pathways that have been overlooked by isolated profiling approaches and to gain insight into which changes are causal, compensatory, correlational, and consequential. In our work, we found that glutathione metabolism is a key pathway of muscle stem cell aging that involves a compensatory feedback loop. Follow-up experiments showed that old muscle stem cells actually form a dichotomy between glutathione-high muscle stem cells and glutathione-low muscle stem cells. RNA-Seq showed that glutathione-high old muscle stem cells are able to synthesize adequate glutathione and thus compensate adequately for oxidative stress with increased glutathione turnover, while glutathione-low old muscle stem cells have failed to compensate for oxidative stress metabolically and instead show increased inflammatory signaling.
2023-03-20 | GSE152793 | GEO
Project description:Multiomics profiling of young and old quiescent skeletal muscle stem cells
| PRJNA640416 | ENA
Project description:Multiomics profiling of young and old quiescent skeletal muscle stem cells [aging WGBS]
| PRJNA640418 | ENA
Project description:Multiomics profiling of young and old quiescent skeletal muscle stem cells [aging RNA-seq]
| PRJNA640409 | ENA
Project description:Multiomics profiling of young and old quiescent skeletal muscle stem cells [GSH RNA-seq]
| PRJNA640417 | ENA
Project description:Aging impairs tissue repair. This is pronounced in skeletal muscle, whose regeneration by muscle stem cells (MuSCs) is robust in young adult animals but inefficient in older organisms. Despite this functional decline, old MuSCs are amenable to rejuvenation through strategies that improve the systemic milieu, such as heterochronic parabiosis. One such strategy, exercise, has long been appreciated for its benefits on healthspan, but its effects on aged stem cell function in the context of tissue regeneration are incompletely understood. Here we show that exercise in the form of voluntary wheel running accelerates muscle repair in old animals and improves old MuSC function. Through transcriptional profiling and genetic studies, we discovered that the restoration of old MuSC activation ability hinges on restoration of Cyclin D1, whose expression declines with age in MuSCs. Pharmacologic studies revealed that Cyclin D1 maintains MuSC activation capacity by repressing TGFβ signaling. Taken together, these studies demonstrate that voluntary exercise is a practicable intervention for old MuSC rejuvenation. Furthermore, this work highlights the distinct role of Cyclin D1 in stem cell quiescence.
| S-EPMC7323974 | biostudies-literature
Project description:Muscle stem cells (MuSCs) persist in a quiescent state and activate in response to specific stimuli. The quiescent state is both actively maintained and dynamically regulated. However, analyses of quiescence have come primarily from cells removed from their niche. Although these cells are still quiescent, biochemical changes certainly occur during the isolation process. Here, we analyze the transcriptome of MuSCs in vivo utilizing MuSC-specific labeling of RNA. Notably, labeling transcripts during the isolation procedure revealed very active transcription of specific subsets of genes. However, using the transcription inhibitor ?-amanitin, we show that the ex vivo transcriptome remains largely reflective of the in vivo transcriptome. Together, these data provide perspective on the molecular regulation of the quiescent state at the transcriptional level, demonstrate the utility of these tools for probing transcriptional dynamics in vivo, and provide an invaluable resource for understanding stem cell state transitions.
| S-EPMC5711481 | biostudies-literature
Project description:Intestinal barrier dysfunction leads to microbial translocation (MT) and inflammation in vertebrate and invertebrate animal models. Age is recently recognized as a factor leading to MT, and in some human and animal model studies, MT was associated with physical function. We evaluated sarcopenia, inflammation, MT biomarkers, and muscle insulin sensitivity in healthy female vervet monkeys (6-27 years old). Monkeys were fed consistent diets and had large and varied environments to facilitate physical activity, and stable social conditions. Aging led to sarcopenia as indicated by reduced walking speeds and muscle mass, but general metabolic health was similar in older monkeys (n = 25) as compared to younger ones (n = 26). When older monkeys were physically active, their MT burden approximated that in young monkeys; however, when older monkeys were sedentary, MT burden was dramatically increased. MT levels were positively associated with inflammatory burden and negatively associated with skeletal muscle insulin sensitivity. Time spent being active was positively associated with insulin sensitivity as expected, but this relationship was specifically modified by the individual monkey's MT, not inflammatory burden. Our data supports clinical observations that MT interacts with physical function as a factor in healthy aging.
| S-EPMC5005918 | biostudies-literature