Fine-Tuning of PGC1α Expression Regulates Cardiac Function and Longevity
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PROVIDER: PRJNA563670 | ENA |
REPOSITORIES: ENA
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Project description:Fine-Tuning of PGC1α Expression Regulates Cardiac Function and Longevity (RNA-seq: WT vs PKI)
| PRJNA563626 | ENA
Project description:Fine-Tuning of PGC1α Expression Regulates Cardiac Function and Longevity (RNA-seq: telomerase-deficient vs PGC1aOE)
| PRJNA558760 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-08-01 | GSE136787 | GEO
Project description:PGC1alpha plays an important role in energy metabolism and mitochondrial function in the heart, multiple attempts have failed to upregulate PGC1alpha expression as a therapy, with the underlying mechanism to be answered. We used RNA sequencing to detail the global programme of gene expression in the hearts of wild-type mice with or without cardiomyocyte-restricted PGC1alpha overexpression.
2022-08-01 | GSE136770 | GEO
Project description:PGC1alpha plays an important role in energy metabolism and mitochondrial function in the heart, multiple attempts have failed to upregulate PGC1alpha expression as a therapy, with the underlying mechanism to be answered. We used RNA sequencing to detail the global programme of gene expression in the hearts of third generation of telomerase-deficient mice with or without cardiomyocyte-restricted PGC1alpha overexpression.
2022-08-01 | GSE135404 | GEO
Project description:Peroxisome proliferator-activated receptor (PPAR) γ coactivator 1α (PGC1α) is a coactivator of various nuclear receptors and other transcription factors that shows increased expression in skeletal muscle during exercise. In skeletal muscle, PGC1α is considered to be involved in contractile protein function, mitochondrial function, metabolic regulation, intracellular signaling, and transcriptional responses. Several isoforms of PGC1α mRNA have recently been identified. PGC1α-a is a full-length isoform of PGC1α that was the first to be isolated. PGC1α-b is another isoform of PGC1α, which is considered to be similar in function to PGC1α-a, differing by only 16 amino acids at the amino terminus. We have previously generated independent lines of transgenic mice that overexpress PGC1α-a or PGC1α-b in skeletal muscle. The microarray data shows that energy metabolism-related pathways such as the TCA cycle, branched-chain amino acid metabolism, purine nucleotide pathway, and malate–aspartate shuttle are activated in PGC1α transgenic mice compared with wild-type mice. For microarray analysis, RNA was isolated from the gastrocnemius skeletal muscle of wild-type control mice (12 weeks of age) as well as transgenic mice [PGC1α-a (E) (Miura et al., J. Biol. Chem. 278:31385-90, 2003), 12 weeks of age; PGC1α-b (02-1) (Miura et al., Endocrinology 149:4527-33, 2008), 14 weeks of age; and PGC1α-b (03-2) (Miura et al., Endocrinology 2008), 14 weeks of age]. Samples from wild-type and transgenic mice (N = 5 for each group) were pooled before use.
2015-09-18 | E-GEOD-67049 | biostudies-arrayexpress
Project description:RATIONALE:PGC1? (peroxisome proliferator-activated receptor gamma coactivator 1?) represents an attractive target interfering bioenergetics and mitochondrial homeostasis, yet multiple attempts have failed to upregulate PGC1? expression as a therapy, for instance, causing cardiomyopathy. OBJECTIVE:To determine whether a fine-tuning of PGC1? expression is essential for cardiac homeostasis in a context-dependent manner. METHODS AND RESULTS:Moderate cardiac-specific PGC1? overexpression through a ROSA26 locus knock-in strategy was utilized in WT (wild type) mice and in G3Terc-/- (third generation of telomerase deficient; hereafter as G3) mouse model, respectively. Ultrastructure, mitochondrial stress, echocardiographic, and a variety of biological approaches were applied to assess mitochondrial physiology and cardiac function. While WT mice showed a relatively consistent PGC1? expression from 3 to 12 months old, age-matched G3 mice exhibited declined PGC1? expression and compromised mitochondrial function. Cardiac-specific overexpression of PGC1? (PGC1?OE) promoted mitochondrial and cardiac function in 3-month-old WT mice but accelerated cardiac aging and significantly shortened life span in 12-month-old WT mice because of increased mitochondrial damage and reactive oxygen species insult. In contrast, cardiac-specific PGC1? knock in in G3 (G3 PGC1?OE) mice restored mitochondrial homeostasis and attenuated senescence-associated secretory phenotypes, thereby preserving cardiac performance with age and extending health span. Mechanistically, age-dependent defect in mitophagy is associated with accumulation of damaged mitochondria that leads to cardiac impairment and premature death in 12-month-old WT PGC1?OE mice. In the context of telomere dysfunction, PGC1? induction replenished energy supply through restoring the compromised mitochondrial biogenesis and thus is beneficial to old G3 heart. CONCLUSIONS:Fine-tuning the expression of PGC1? is crucial for the cardiac homeostasis because the balance between mitochondrial biogenesis and clearance is vital for regulating mitochondrial function and homeostasis. These results reinforce the importance of carefully evaluating the PGC1?-boosting strategies in a context-dependent manner to facilitate clinical translation of novel cardioprotective therapies.
| S-EPMC6742548 | biostudies-literature
Project description:Aging is a complex process involving multiple pathways, each of which takes place and dominates at various stages of aging. It is largely unclear how these pathways coordinate with each other and take turns to function. Here we focus on microRNAs (miRNAs), for their multi-targeting, fine-tuning nature, and thus a potential to act as systems–level anti-aging regulator. We used C. elegans treated with dietary restriction as an anti-aging model to reveal how miRNAs link the regulatory modules of different stages to convert starvation signal into longevity benefits. miRNAs show a delayed response pattern upon DR, repress early response genes and fine-tune late response genes.
2021-07-25 | GSE134925 | GEO
Project description:Loss of function during ageing is accompanied by transcriptional drift, altering gene expression and contributing to a variety of age-related diseases. CREB-regulated transcriptional coactivators (CRTCs) have emerged as key regulators of gene expression that might be targeted to promote longevity. Here, we define the role of the Caenorhabditis elegans CRTC-1 in the epigenetic regulation of longevity. Endogenous CRTC-1 binds chromatin factors, including components of the COMPASS complex, which trimethylates lysine 4 on histone H3 (H3K4me3). CRISPR editing of endogenous CRTC-1 reveals that the CREB-binding domain in neurons is specifically required for H3K4me3-dependent longevity. However, this effect is independent of CREB but instead acts via the transcription factor AP-1. Strikingly, CRTC-1 also mediates global histone acetylation levels, and this acetylation is essential for H3K4me3-dependent longevity. Indeed, overexpression of an acetyltransferase enzyme is sufficient to promote longevity in wild-type worms. CRTCs, therefore, link energetics to longevity by critically fine-tuning histone acetylation and methylation to promote healthy ageing.
2023-08-02 | GSE239572 | GEO
Project description:Fine-tuning of a CRISPRi screen in the seventh pandemic Vibrio cholerae
| PRJEB76123 | ENA