Effect of age, calorie restriction and resveratrol on gene expression in mouse heart, brain, and skeletal muscle
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE11291 | GEO | 2008/06/10
SECONDARY ACCESSION(S): PRJNA106707
REPOSITORIES: GEO
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Project description:Resveratrol in high doses has been shown to extend lifespan in some studies in invertebrates and to prevent early mortality in mice fed a high-fat diet. We fed mice from middle age (14-months) to old age (30-months) either a control diet, a low dose of resveratrol (4.9 mg kg-1 day-1), or a calorie restricted (CR) diet and examined genome-wide transcriptional profiles. We report a striking transcriptional overlap of CR and resveratrol in heart, skeletal muscle and brain. Both dietary interventions inhibit gene expression profiles associated with cardiac and skeletal muscle aging. Gene expression profiling suggests that both CR and resveratrol may retard some aspects of aging through alterations in chromatin structure and transcription. Resveratrol, at doses that can be readily achieved in humans, fulfills the definition of a dietary compound that mimics some aspects of CR. Experiment Overall Design: Heart, neocortex tissue, and gastrocnemius muscle was collected from young and old mice at 5 and 30 months of age, respectively; mice were subjected to either a calorie restricted diet or a control diet supplemented with resveratrol
2008-06-18 | E-GEOD-11291 | biostudies-arrayexpress
Project description:Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending lifespan A small molecule that safely mimics the ability of dietary restriction (DR) to delay age-related diseases in laboratory animals is greatly sought after. We and others have shown that resveratrol mimics effects of DR in lower organisms. In mice, we find that resveratrol induces gene expression patterns in multiple tissues that parallel those induced by DR and every-other-day feeding. Moreover, resveratrol-fed elderly mice shows a marked reduction in signs of aging including reduced albuminuria, decreased inflammation and apoptosis in the vascular endothelium, increased aortic elasticity, greater motor coordination, reduced cataract formation, and preserved bone mineral density. However, mice fed a standard diet did not live longer when treated with resveratrol beginning at mid-life. Our findings indicate that resveratrol treatment has a range of beneficial effects in mice but does not increase the longevity of ad libitum-fed animals when started mid-life. Male C57BL/6NIA mice at 11 months of age were maintained on a standard purified mouse diet (AIN-93G) for one month prior to the start of the experiment. Beginning at one year of age, SD and EOD groups were fed a standard AIN-93G diet or AIN-93G plus 0.01% or 0.04% resveratrol for the duration of the study. Three separate groups were placed on an HC diet (AIN-93G modified by the addition of hydrogenated coconut oil to provide 60% of calories from fat) or HC + 0.01% or 0.04% resveratrol 6 weeks later and remained on those diets throughout the study. SD and HC mice were fed ad libitum. EOD mice were fed ad libitum on alternate days then moved to a separate cage without food for 24 h. Food intake and body weight were measured on a weekly basis for the duration of the study.
2008-08-04 | E-GEOD-11845 | biostudies-arrayexpress
Project description:Although caloric restriction (CR) was first shown to extend the lifespan of rodents over 75 years ago, the underlying mechanisms remain unclear. Additionally, the majority of published studies have focused on the effects of short-term CR. To better understand cell signaling alterations in a tissue known to be highly impacted by CR, we sought to assess the impact of aging and lifelong CR on skeletal muscle protein phosphorylation dynamics. We performed phosphoproteomic analysis on skeletal muscle from young mice, old mice fed on an ad libitum diet, and old mice fed a CR diet. This analysis revealed distinct phosphoproteomic signatures associated with both aging and diet. Importantly, CR appeared to promote a signature that was more similar to young mice than old mice fed on an ad lib diet. From the phosphorylation measurements on its known substrates, we deciphered that aging promotes Protein kinase A (PKA) signaling, and CR inhibits this signaling cascade. Given the demonstrated role of PKA signaling as a “pro-aging” pathway in various model organisms, including yeast and mice, we propose that CR exerts its longevity-enhancing effects partially via the suppression of this pathway.
2021-01-30 | PXD018455 | JPOST Repository
Project description:Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending lifespan A small molecule that safely mimics the ability of dietary restriction (DR) to delay age-related diseases in laboratory animals is greatly sought after. We and others have shown that resveratrol mimics effects of DR in lower organisms. In mice, we find that resveratrol induces gene expression patterns in multiple tissues that parallel those induced by DR and every-other-day feeding. Moreover, resveratrol-fed elderly mice shows a marked reduction in signs of aging including reduced albuminuria, decreased inflammation and apoptosis in the vascular endothelium, increased aortic elasticity, greater motor coordination, reduced cataract formation, and preserved bone mineral density. However, mice fed a standard diet did not live longer when treated with resveratrol beginning at mid-life. Our findings indicate that resveratrol treatment has a range of beneficial effects in mice but does not increase the longevity of ad libitum-fed animals when started mid-life.
2008-08-05 | GSE11845 | GEO
Project description:Calorie restriction (CR) is a dietary regimen that supports healthy aging. In this study we investigated the systemic and liver-specific responses caused by a diet switch to a medium-fat (MF) diet in 24-month-old life-long, CR-exposed mice. This study aimed to increase the knowledge base on dietary alterations of gerontological relevance. Nine-week-old C57BL/6J mice were exposed either to a control, CR or MF diet. At the age of 24 months, a subset of mice of the CR group was transferred to ad libitum MF feeding (CR-MF).The mice were sacrificed at the age of 28 months, then biochemical and molecular analyses were performed. Our results showed that, despite the long-term exposure to the CR regimen, mice in the CR-MF group displayed hyperphagia, rapid weight gain, and hepatic steatosis. However, no hepatic fibrosis/injury or alteration in CR-improved survival was observed in the diet switch group. The liver transcriptomic profile of CR-MF mice largely shifted to a profile similar to the MF-fed animals but leaving ~22% of the 1578 differentially regulated genes between the CR and MF diet groups comparable with the expression of the life-long CR group. Therefore, although the diet switch was performed at an old age, the CR-MF-exposed mice showed plasticity in coping with the challenge of a MF diet without developing severe liver pathologies.
2018-01-24 | GSE102593 | GEO
Project description:We used Affymetrix microarrays to investigate gene expression changes in PBMNCs isolated from female and male pigs to determine significant modulatory effects that may have been induced by the intake of resveratrol during 9 months in high-fat fed animals . The aim of this work was to determine whether the intake of dietary levels of resveratrol (RES) exerted any modulatory effects, at the level of gene expression, in PBMNCs isolated from female and male pigs exposed to a H-F diet for 9 months. We first isolated PBMNCs, and the corresponding total RNA, from 5 female pigs and 5 male pigs at time 0 (beginning of the experiment) to determine basal gene expression levels and to compare sex differential gene expression. Animals designated to the control group were then fed a normal chow (5% beef tallow) for 9 months. Animals in the H-F diet were fed a chow with 20% of beef tallow and animals in the H-F diet supplemented with resveratrol were fed the 20% fat diet plus resveratrol (8 mg/Kg body weight per day). From each group, PBMNCs were isolated from 2 female and 2 male animals. Pure RNA was extracted from the PBMNCs for microarrays analyses (Affymetrix) and gene differential expression determined between the H-F fed animals and CT animals (to determine the effects of fat consumption) and between the H-F fed animals supplemented with RES and the H-F group (to determine the effects of RES on the fat consumption).
2010-08-08 | E-GEOD-23503 | biostudies-arrayexpress
Project description:We used Affymetrix microarrays to investigate gene expression changes in PBMNCs isolated from female and male pigs to determine significant modulatory effects that may have been induced by the intake of GE and (or) RES during 4 months in animals fed an atherogenic diet (AD) . The aim of this work was to determine whether the intake of low doses of a Grape Extract (GE; 1 g/70 Kg animal body weight) and (or) Resveratrol (RES; 18 mg/70 Kg animal body weight) exerted any modulatory effects, at the level of gene expression, in PBMNCs isolated from female and male pigs exposed to an atherogenic diet (AD) for 4 months. We isolated PBMNCs, and the corresponding total RNA, from 2 female and 2 male pigs for each group. Pure RNA was extracted from the PBMNCs for microarrays analyses (Affymetrix) and gene differential expression determined between the AD fed animals and control (CT) animals (to determine the effects of a high-fat consumption) and between the AD fed animals supplemented with GE and (or) RES and the animals fed the AD diet alone (to determine the effects of GE and (or) RES on the fat consumption). In addition, the effects of the consumption of GE and RES against a standard control diet (CT) were also determined. Differential gene expression: 1) AD vs CT (response to exposure to a high-fat diet); 2) AD-GE vs AD (modulatory effects of the intake of a grape extract on high-fat fed animals); 3) AD-GE-RES vs AD (modulatory effects of the intake of a resveratrol-enriched grape extract on high-fat fed animals); 4) AD-RES vs AD (modulatory effects of the intake of resveratrol on high-fat fed animals); 5) CT-GE-RES vs CT (modulatory effects of the intake of a resveratrol-enriched grape extract on animals fes a standard pig chow).
2011-07-22 | E-GEOD-30874 | biostudies-arrayexpress
Project description:Since the liver is the central organ of metabolism, changes in diet have a great impact on this organ and overall on health with aging. It is well known that dietary fat source strongly influences many parameters of the hepatic mitochondria. These changes includes modification of lipid composition of mitochondrial membrane, affecting the mtETC functions, oxidative stress and mtDNA alterations. We used microarrays to detail the changes in gene expression provides by feeding lifelong on different dietary fat sources, and identified distinct classes of up and down-regulated genes during aging under different dietary conditions. Rats were fed lifelong on a normolipidic diet (4% w/w) with virgin olive, sunflower or fish oil as dietary fat source. At 6 and 24 months, animals were killed and liver were removed for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain changes in gene expression due to both aging and dietary conditions. There were 6 experimental groups (virgin olive oil at 6 months, sunflower oil at 6 months, fish oil at 6 months, virgin olive oil at 24 months, sunflower oil at 24 months and fish oil at 24 months. 3 animals were studied of each experimental group, so a total of 18 samples were analyzed.
2014-03-26 | E-GEOD-56166 | biostudies-arrayexpress
Project description:Calorie restriction (CR) consistently extends longevity and delays age-related diseases across several animal models. We have previously shown that different dietary fat sources can modulate life span and mitochondrial ultrastructure, function and membrane fatty acid composition in mice maintained on a 40% CR. In particular, animals consuming lard as the main fat source (CR-Lard) lived longer than CR mice consuming diets with soybean oil (CR-Soy) or fish oil (CR-Fish) as the predominant lipid source. In the present work, a transcriptomic analysis in liver and skeletal muscle was performed in order to elucidate possible mechanisms underlying the changes in energy metabolism and longevity induced by dietary fat in CR mice. After 8 months of CR, transcription downstream of several mediators of inflammation was inhibited in liver. In contrast, proinflammatory signaling was increased in the CR-Fish versus other CR groups. Dietary fish oil induced a gene expression pattern consistent with increased transcriptional regulation by several cytokines (TNF, GM-CSF, TGF-b) and sex hormones when compared to the other CR groups. The CR-Fish also had lower expression of genes involved in fatty acid biosynthesis and increased expression of mitochondrial and peroxisomal fatty acid b-oxidation genes than the other CR diet groups. Our data suggest that a diet high in n-3 PUFA, partially reverts CR-related changes in gene expression of key processes, such as inflammation and steroid hormone signaling, and this may mitigate life span extension with CR in mice consuming diets high in fish oil. Sixteen male C57BL/6 mice were purchased at 14 weeks of age from the Jackson Laboratory (Sacramento, CA) and fed a commercial rodent chow diet (Harlan Teklad #7012). The mice were allowed ad libitum access to food and their food intake was monitored for two weeks. At 4 months of age, the animals were randomly assigned to four groups. The Control group received 95% of the daily ad libitum caloric intake (13.6 kcal/day) to avoid excessive weight gain and obesity, and the other three groups received 60% of the ad libitum consumption (8.6 kcal/day). A total of 31 mice samples (eight control, eight fish, eight lard and seven soy distributed in liver (n=16) and muscle (n=15) tissues) were analyzed by RNA-Sequencing. However, 2 samples (1071 control liver [JFM42H], 1125 fish muscle [JFM45D]) were discarded for further analysis after performing cluster analysis (they were clustering in a different groups). Also their RIN values were not as high as those of the other samples, indicating lower quality of the RNA.
2015-08-10 | E-GEOD-71773 | biostudies-arrayexpress
Project description:Caloric restriction (CR) can delay morbidity and mortality in a broad range of species, including mice and macaques. Mutations and chemical agents, such as resveratrol or rapamycin that partly mimic the CR effect, can similarly increase survival or extend lifespan. In humans, however, the effects of CR or other life-extending agents have not been investigated systematically. Humans already display lower mortality and greater maximal lifespan compared to closely related species, including chimpanzees and macaques. It is thus possible that humans, during their evolution, have acquired genetic mutations mimicking the CR effect. To address this question, we compared transcriptome differences between humans and other primates, with transcriptome changes observed in mice subjected to CR [see references below]. We show that the human transcriptome state examined in multiple tissues and across different ages resembles the transcriptome state of mice fed ad libitum, relative to CR mice or mice treated with resveratrol. Furthermore, transcriptome changes induced by CR were enriched among genes showing age-related changes among primates, concentrated in specific expression patterns, and could be linked with specific functional pathways, including insulin signalling, cancer, and immune response. These findings indicate that the evolution of human longevity was likely independent of CR-induced lifespan extension mechanisms. Consequently, application of CR or CR-mimicking agents may offer a promising direction in the extension of healthy human lifespan. References for the transcriptome changes observed in mice subjected to CR: 1) Barger JL, Kayo T, Vann JM, Arias EB, Wang J, Hacker TA, Wang Y, Raederstorff D, Morrow JD, Leeuwenburgh C, et al: A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS One 2008, 3:e2264. 2) Tsuchiya T, Dhahbi JM, Cui X, Mote PL, Bartke A, Spindler SR: Additive regulation of hepatic gene expression by dwarfism and caloric restriction. Physiol Genomics 2004, 17:307-315. 3) Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, et al: Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006, 444:337-342.
2013-02-28 | GSE44147 | GEO