MRNA and miRNA expression profiling in myocardial tissue by caloric restriction initiated in different aged mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus Rattus norvegicus Homo sapiens
PROVIDER: GSE89909 | GEO | 2016/11/17
SECONDARY ACCESSION(S): PRJNA354270
REPOSITORIES: GEO
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Project description:Using the highly sensitive miRNA array, we assessed the effect of CR, beginning in different ages, on modulating miRNAs expression in the heart and found miRNAs were related to cardiac aging and changed differently after 3 months CR during aging.
2016-11-17 | GSE89908 | GEO
Project description:The pathway analysis of differentially expressed genes (DEGs) demonstrated that some altered pathways, such as p53, cell cycle, and TGFb signaling pathways were closely associated with cardiac aging. Notably, FOXO signaling pathway revealed significant differences between CR initiated in different aged mice
2016-11-17 | GSE89907 | GEO
Project description:mRNA and miRNA expression profiling in myocardial tissue by caloric restriction initiated in different aged mice
| PRJNA354270 | ENA
Project description:Caloric Restriction in Leptin Deficiency Worsens Myocardial Steatosis: Failure to Upregulate PPAR gamma and Thermogenic Glyecrolipid/Fatty Acid Cycling Growing evidence supports an anti-lipotoxic role for leptin in preventing inappropriate peripheral tissue lipid deposition. Obese, leptin deficient ob/ob mice develop left ventricular (LV) hypertrophy and myocardial steatosis with increased apoptosis and decreased longevity. Here we investigated the cardiac effects of caloric restriction in leptin deficiency. Echocardiography was performed on C57Bl/6 wild-type mice (WT) and 7-month-old ob/ob mice fed ad lib, leptin-repleted (LR-ob/ob), or calorie-restricted (CR-ob/ob) for four weeks. Ventricular tissue was examined by electron microscopy (EM), mitochondrial coupling assay, and microarray expression profiling. LR and CR-ob/ob mice showed decreased body weight, heart weight, and LV wall thickness compared to ad lib ob/ob mice. LV fractional shortening was decreased in ad lib ob/ob mice, but restored to WT levels in LR and CR groups. However, EM revealed severe cardiac steatosis in the CR-ob/ob group compared to only moderate steatosis in ad lib ob/ob . Despite marked cardiac steatosis, CR (like LR) restored mitochondrial coupling to WT levels. CR up-regulated genes associated with oxidative stress and cell death, changes suggestive of cardiac lipotoxicity. LR, but not CR was shown to induce core genes involved in glycerolipid/free fatty acid cycling, a highly thermogenic pathway that can reduce intracellular lipid stores. LR, but not CR up-regulated and restored PGC1 and PPARto wild type levels; CR paradoxically further suppressed cardiac PPAR. Thus, leptin is essential in protecting the heart from lipotoxicity, and the inability to up-regulate the thermogenic glycerolipid/free fatty acid cycling pathway may impair the response of leptin deficient animals to the lipotoxic stress of calorie restriction. 6 month aged ob/ob mice were either leptin repleted with osmotic mini-pumps, calorie restricted to match the caloric intake of the leptin repleted mice, or fed ad lib for one month. 6-8 month C57Bl/6J mice were aged to serve as controls.
2011-04-29 | E-GEOD-16790 | biostudies-arrayexpress
Project description:Advanced maternal age and ovarian aging are deleterious to the quantity and quality of oocytes and epigenetic modifications, which can affect the health of offspring. However, relatively little is known about the regulation of microRNA-mediated transcription during ovarian aging. We therefore aimed to identify age-related mRNA and microRNA changes and their interactions in the ovaries of aged mice. We performed QuantSeq 3'mRNA and small RNA sequencing to compare their expression patterns in post-ovulation ovaries from young (12-week-old) and old (44-week-old) mice. Functional annotation and integrative analyses were performed to identify the potential functions of differentially expressed genes and identify binding sites for critical microRNAs. We found 343 differentially expressed genes and 9 microRNAs in our comparison of the two mouse groups, with fold changes >2.0 (P < 0.01). Furthermore, we identified possible direct interactions between 24 differentially expressed mRNAs and 8 microRNAs. The differentially expressed genes are involved in fat digestion and absorption, the PI3K-Akt signaling pathway, serotonergic synapse, and ovarian steroidogenesis, which are important for folliculogenesis and oocyte growth. During ovarian aging, changes in gene expression induce alterations in folliculogenesis, oocyte growth, and steroidogenesis, resulting in decreased oocyte quality and reproductive outcomes.
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Project description:Caloric Restriction in Leptin Deficiency Worsens Myocardial Steatosis: Failure to Upregulate PPAR gamma and Thermogenic Glyecrolipid/Fatty Acid Cycling Growing evidence supports an anti-lipotoxic role for leptin in preventing inappropriate peripheral tissue lipid deposition. Obese, leptin deficient ob/ob mice develop left ventricular (LV) hypertrophy and myocardial steatosis with increased apoptosis and decreased longevity. Here we investigated the cardiac effects of caloric restriction in leptin deficiency. Echocardiography was performed on C57Bl/6 wild-type mice (WT) and 7-month-old ob/ob mice fed ad lib, leptin-repleted (LR-ob/ob), or calorie-restricted (CR-ob/ob) for four weeks. Ventricular tissue was examined by electron microscopy (EM), mitochondrial coupling assay, and microarray expression profiling. LR and CR-ob/ob mice showed decreased body weight, heart weight, and LV wall thickness compared to ad lib ob/ob mice. LV fractional shortening was decreased in ad lib ob/ob mice, but restored to WT levels in LR and CR groups. However, EM revealed severe cardiac steatosis in the CR-ob/ob group compared to only moderate steatosis in ad lib ob/ob . Despite marked cardiac steatosis, CR (like LR) restored mitochondrial coupling to WT levels. CR up-regulated genes associated with oxidative stress and cell death, changes suggestive of cardiac lipotoxicity. LR, but not CR was shown to induce core genes involved in glycerolipid/free fatty acid cycling, a highly thermogenic pathway that can reduce intracellular lipid stores. LR, but not CR up-regulated and restored PGC1-alpha and PPAR-alpha to wild type levels; CR paradoxically further suppressed cardiac PPAR-alpha. Thus, leptin is essential in protecting the heart from lipotoxicity, and the inability to up-regulate the thermogenic glycerolipid/free fatty acid cycling pathway may impair the response of leptin deficient animals to the lipotoxic stress of calorie restriction.
2011-04-29 | GSE16790 | GEO
Project description:Fear extinction learning, the ability to reassess a learned cue of danger as safe when it no longer predicts aversive events, is often dysregulated in anxiety disorders. Selective serotonin reuptake inhibitors (SSRI's) enhance neural plasticity and their ability to enhance fear extinction learning may explain their anxiolytic properties. Caloric restriction (CR) has SSRI-like effects on neural plasticity and anxiety-related behavior. We implemented CR in mice to determine its effects on conditioned-fear responses. Wild type and serotonin transporter (SERT) knockout mice underwent CR for 7 days leading to significant weight loss. Mice were then tested for cued fear learning and anxiety-related behavior. CR markedly enhanced fear extinction learning and its retention in adolescent female mice, and adults of both sexes. These effects of CR were absent in SERT knockout mice. Moreover, CR phenocopied behavioral and molecular effects of chronic fluoxetine, but there was no additive effect of CR in fluoxetine-treated mice. These results demonstrate that CR enhances fear extinction learning through a SERT-dependent mechanism. These results may have implications for eating disorders such as anorexia nervosa (AN), in which there is a high prevalence of anxiety before the onset of dietary restriction and support proposals that in AN, CR is a motivated effort to control dysregulated fear responses and elevated anxiety.
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Project description:Caloric restriction (CR) without malnutrition has been shown to retard several aspects of the aging process and to extend lifespan in different species. There is strong interest in the identification of CR mimetics (CRMs), compounds that mimic the beneficial effects of CR on lifespan and healthspan without restriction of energy intake. Identification of CRMs in mammals is currently inefficient due to the lack of screening tools. We have performed whole-genome transcriptional profiling of CR in seven mouse strains (C3H/HeJ, CBA/J, DBA/2J, B6C3F1/J, 129S1/SvImJ, C57BL/6J, and BALB/cJ) in white adipose tissue (WAT), gastrocnemius muscle, heart, and brain neocortex. This analysis has identified tissue-specific panels of genes that change in expression in multiple mouse strains with CR. We validated a subset of genes with qPCR and used these to evaluate the potential CRMs bezafibrate, pioglitazone, metformin, resveratrol, quercetin, 2,4-dinitrophenol, and L-carnitine when fed to C57BL/6J 2-month-old mice for 3 months. Compounds were also evaluated for their ability to modulate previously characterized biomarkers of CR, including mitochondrial enzymes citrate synthase and SIRT3, plasma inflammatory cytokines TNF-α and IFN-γ, glycated hemoglobin (HbA1c) levels and adipocyte size. Pioglitazone, a PPAR-γ agonist, and L-carnitine, an amino acid involved in lipid metabolism, displayed the strongest effects on both the novel transcriptional markers of CR and the additional CR biomarkers tested. Our findings provide panels of tissue-specific transcriptional markers of CR that can be used to identify novel CRMs, and also represent the first comparative molecular analysis of several potential CRMs in multiple tissues in mammals.
| S-EPMC5506434 | biostudies-literature
Project description:Calorie restriction (CR) increases average and maximum lifespan and exhibits an apparent beneficial impact on age-related diseases. Several studies have shown that CR initiated either in middle or old age could improve ischemic tolerance and rejuvenate the aging heart; however, the data are not uniform when initiated in young. The accurate time to initiate CR providing maximum benefits for cardiac remodeling and function during aging remains unclear. Thus, whether a similar degree of CR initiated in mice of different ages could exert a similar effect on myocardial protection was investigated in this study. C57BL/6 mice were subjected to a calorically restricted diet (40% less than the ad libitum diet) for 3 months initiated in 3, 12, and 19 months. It was found that CR significantly reversed the aging phenotypes of middle-aged and old mice including cardiac remodeling (cardiomyocyte hypertrophy and cardiac fibrosis), inflammation, mitochondrial damage, telomere shortening, as well as senescence-associated markers but accelerated in young mice. Furthermore, whole-genome microarray demonstrated that the AMP-activated protein kinase (AMPK)-Forkhead box subgroup 'O' (FOXO) pathway might be a major contributor to contrasting regulation by CR initiated in different ages; thus, increased autophagy was seen in middle-aged and old mice but decreased in young mice. Together, the findings demonstrated promising myocardial protection by 40% CR should be initiated in middle or old age that may have vital implications for the practical nutritional regimen.
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