Tomatidine Attenuates Inflammatory Responses to Exercise-Like Stimulation in Donor-derived Skeletal Muscle Myobundles
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE296683 | GEO | 2025/08/27
REPOSITORIES: GEO
Similar Datasets
Project description:Tomatidine Attenuates Inflammatory Responses to Exercise-Like Stimulation in Donor-derived Skeletal Muscle Myobundles
| PRJNA1260522 | ENA
Project description:Aging is a major international concern and brings with it formidable socioeconomical and healthcare challenges. An attainable approach to improve general health in humans is using small molecules. Tomatidine, a natural compound abundant in unripe tomatoes, inhibits aging-related skeletal muscle atrophy in mice. Here we show that tomatidine extends lifespan and healthspan in the aging animal model C. elegans, which shares many major longevity pathways with those of mammals. Tomatidine improves behaviors related to healthspan, including increased pharyngeal pumping and swimming movement, and also reduces deterioration of muscle cells in worms. Microarray, imaging, and behavioral analysis reveal that tomatidine maintains mitochondrial homeostasis through mitochondrial biogenesis and PINK-1/DCT-1-dependent mitophagy. Mechanistically, tomatidine induces mitochondrial hormesis by mildly inducing ROS production, which in turn activates the cellular antioxidant response SKN-1/Nrf2 pathway, followed by increased mitophagy in worms, primary rat neurons, and human cells. Our data suggest that tomatidine may delay some physiological aspects of aging, and points to new approaches for pharmacological interventions towards diseases of aging.
2017-08-21 | GSE85237 | GEO
Project description:Exercise affects the expression of microRNAs (miR/s) and muscle-derived extracellular vesicles (EVs). To evaluate sarcoplasmic and secreted miR expression in human skeletal muscle in response to exercise-mimetic contractile activity, we utilized a three-dimensional tissue-engineered model of human skeletal muscle (“myobundles”). Myobundles were subjected to three culture conditions: no electrical stimulation (CTL), chronic low frequency stimulation (CLFS), or intermittent high frequency stimulation (IHFS) for 7 days. RNA was isolated from myobundles and from extracellular vesicles (EVs) secreted by myobundles into culture media; miR abundance was analyzed by miRNA-sequencing. We used edgeR and a within-sample design to evaluate differential miR expression and Pearson correlation to evaluate correlations between myobundle and EV populations within treatments with statistical significance set at p<0.05. Numerous miRs were differentially expressed between myobundles and EVs; 116 miRs were differentially expressed within CTL, 3 within CLFS, and 2 within IHFS. Additionally, 25 miRs were significantly correlated (18 in CTL, 5 in CLFS, 2 in IHFS) between myobundles and EVs. Electrical stimulation resulted in differential expression of 8 miRs in myobundles and only 1 miR in EVs. Several KEGG pathways, known to play a role in regulation of skeletal muscle, were enriched, with differentially overrepresented miRs between myobundle and EV populations identified using miEAA. Together, these results demonstrate that in vitro exercise-mimetic contractile activity of human engineered muscle affects both their expression of miRs and number of secreted EVs. These results also identify novel miRs of interest for future studies of the role of exercise in organ-organ interactions in vivo
2022-09-28 | GSE203157 | GEO
Project description:For additional details see Ebert et al, Identification and Small Molecule Inhibition of an ATF4-dependent Pathway to Age-related Skeletal Muscle Weakness and Atrophy. Weight-matched cohorts of 22-month-old male C57BL/6 mice were provided ad libitum access to standard chow (control) or standard chow supplemented with 0.27% ursolic acid (UA) or 0.05% tomatidine (TM) for 2 months. After the 2 month treatment period, quadriceps femoris muscles were harvested. mRNA levels in muscles harvested from ursolic acid or tomatidine fed mice were normalized to levels in muscles fed control diet.
2015-09-03 | E-GEOD-72651 | biostudies-arrayexpress
Project description:Cellular senescence contributes to aging and age-related dysfunction across multiple tissues, including the brain. Here, we identify tomatidine, an aglycone of tomatine naturally found in tomatoes, as a senotherapeutic agent. In vitro, tomatidine selectively suppressed SASP expression without affecting p16Ink4a or p21Cip1 levels in senescent human brain microvascular endothelial cells. In aged mice, dietary tomatidine reduced frailty and improved motor coordination and cognitive performance. These functional benefits were accompanied by a reduction in senescence markers (e.g., p16, p21, and telomere-associated DNA damage foci) in liver, skin, and hippocampal neurons, as well as decreased neuroinflammation and microglial activation. Tomatidine also reduced senescence in brain endothelial cells and increased the expression of tight junction–associated proteins. Together, these findings suggest that tomatidine is as a promising senotherapeutic with the potential to preserve cognitive and vascular function during aging. As a naturally occurring compound with oral bioavailability and a favorable safety profile, tomatidine holds strong translational promise for future therapeutic development.
2026-04-03 | GSE312732 | GEO
Project description:Genome-wide expression profiling was used to identify genes that showed altered expression in response to treatment with the fungistatic saponin tomatidine. Overnight batch cultures of strain S288C were diluted to an optical density at 600nm of 0.1. After 1 hour of growth at 30°C, the compounds were added and the cultures were incubated for an additional 5 hours prior to harvesting. Control cultures were treated with the solvent dimethylformamide (DMF). Tomatidine treated cultures were grown in the presence of tomatidine (dissolved in DMF) at concentations of 7.5 uM and 15 uM. Growth inhibition by the compounds was monitored by measuring the OD600nm. Cells were pelleted and frozen in liquid nitrogen. Acid-washed glass beads (0.5 mm diameter; Sigma) were added and the cells disrupted using two 20 s cycles at speed setting 6 in the Savant Bio 101 Fast Prep FP120. Total RNA was isolated using the Qiagen RNeasy kit (Qiagen, Inc., Valencia, CA, USA). Microarray hybridisation was performed using the Affymetrix GeneChip® Yeast genome S98 array using protocols described by Affymetrix, Inc. (Santa Clara, CA, USA) (as previously described (Zhu et al., 2001). Data were analyzed using Affymetrix® Microarray Suite version 5.0 software Keywords: dose response
2004-11-06 | GSE1927 | GEO
Project description:Genome-wide expression profiling was used to identify genes that showed altered expression in response to treatment with the fungistatic saponin tomatidine. Overnight batch cultures of strain S288C were diluted to an optical density at 600nm of 0.1. After 1 hour of growth at 30°C, the compounds were added and the cultures were incubated for an additional 5 hours prior to harvesting. Control cultures were treated with the solvent dimethylformamide (DMF). Tomatidine treated cultures were grown in the presence of tomatidine (dissolved in DMF) at concentations of 7.5 uM and 15 uM. Growth inhibition by the compounds was monitored by measuring the OD600nm. Cells were pelleted and frozen in liquid nitrogen. Acid-washed glass beads (0.5 mm diameter; Sigma) were added and the cells disrupted using two 20 s cycles at speed setting 6 in the Savant Bio 101 Fast Prep FP120. Total RNA was isolated using the Qiagen RNeasy kit (Qiagen, Inc., Valencia, CA, USA). Microarray hybridisation was performed using the Affymetrix GeneChip® Yeast genome S98 array using protocols described by Affymetrix, Inc. (Santa Clara, CA, USA) (as previously described (Zhu et al., 2001). Data were analyzed using Affymetrix® Microarray Suite version 5.0 software
2008-06-11 | E-GEOD-1927 | biostudies-arrayexpress
Project description:Rheumatoid arthritis (RA) is a chronic inflammatory disease, causing pain, increased mortality, and profound disability rates. RA affects articular joints and multiple organs, including skeletal muscle. Loss of muscle mass is associated with increased disability in RA. We developed an in vitro tissue-engineered human skeletal muscle model (myobundle) to better understand the disease mechanisms driving muscle loss in RA. Myobundles were generated using primary skeletal muscle cells from the vastus lateralis muscle of 5 RA patients and 4 age-matched healthy controls. Compared to controls, RA myobundles were more sensitive to IFN-γ, leading to reduced contractile force. Gene sets enriched in IFN-γ-treated RA myobundles, but not IFN-γ-treated controls, were involved in the response to hypoxia and the unfolded protein response. We identified PIM1 as a selectively upregulated gene and verified altered protein expression by Western blotting. Tofacitinib restored contractile force and myosin heavy chain protein levels in RA myobundles with IFN-γ-induced dysfunction. Thus, human myobundles can model inflammation of muscle in RA and other diseases.
2025-03-19 | GSE283881 | GEO
Project description:Global transcriptomic analysis revealed increased gene expression and particularly mitochondrial-related gene expression in microgravity for the electrically stimulated younger myobundles, while the older myobundles were less responsive. Young- and old-derived skeletal muscle myobundles were exposed to microgravity for 12 days and matching ground control group.
2025-07-30 | GSE298393 | GEO
Project description:Genome-wide expression profiling was used to identify genes that showed altered expression in response to treatment with the saponins tomatidine, tomatine and the sterol biosynthesis inhibitory compound fenpropimorph; Growth inhibition by the compounds was monitored by measuring the OD600nm. Cells were pelleted and frozen in liquid nitrogen. Acid-washed glass beads (0.5 mm diameter; Sigma) were added and the cells disrupted using two 20 s cycles at speed setting 6 in the Savant Bio 101 Fast Prep FP120. Total RNA was isolated using the Qiagen RNeasy kit (Qiagen, Inc., Valencia, CA, USA). Microarray hybridisation was performed using the Affymetrix GeneChip® Yeast genome S98 array using protocols described by Affymetrix, Inc. (Santa Clara, CA, USA) (as previously described (Zhu et al., 2001). Data were analyzed using the RMA algorithm using Expressionist Pro (GeneData Inc., Switzerland). Experiment Overall Design: Overnight batch cultures of strain S288C were diluted to an optical density at 600nm of 0.1. After 1 hour of growth at 30°C, the compounds were added and the cultures were incubated for an additional 5 hours prior to harvesting. Control cultures were treated with the solvent dimethylformamide (DMF). Tomatidine treated cultures were grown in the presence of 0.625 ppm tomatidine, 13.9 ppm Tomatine and 0.313 ppm Fenpropimorph, all dissolved in DMF. Each of the three replicates of the cultures produced on 3 independent days.
2007-09-21 | E-GEOD-4669 | biostudies-arrayexpress