Project description:The SIRT1 deacetylase is one of the best-studied potential mediators of some of the anti-aging effects of calorie restriction (CR); but its role in CR-dependent lifespan extension has not been demonstrated. We previously found that mice lacking both copies of SIRT1 displayed a shorter median lifespan than wild type mice on an ad libitum diet. Here we report that median lifespan extension in CR heterozygote SIRT1+/- mice was identical (51%) to that observed in wild type mice but SIRT1+/- mice displayed a higher frequency of some certain pathologies. Although larger studies in different genetic backgrounds are necessary , these results provide strong initial evidence for the requirement of SIRT1 for the anti-aging effects of CR, but suggest that its high expression is not required for CR-induced lifespan extension. Key words: SIRT1, caloric restriction, lifespan, anti-aging 2-5 month old male mice of 3 different genotypes (SIRT1+/+, SIRT1+/-, and SIRT1-/-) that had normal, reduced or no expression of SIRT1 were treated with either a 40% caloric restricted diet (CR) or an ad libitum diet (AL). 2-4 replicates of each experimental condition were used in the analysis.
Project description:To further analyze the effect of aging and caloric restriction in the microRNA expression, we have employed microarray expression profiling as a discovery platform to identify differentially expressed microRNAs in middle-aged animals and the impact of caloric restriction in the microRNA expression profile. Subcutaneous and visceral adipose tissue were extracted from 3 groups of mice: 3 month-old, 12 month-old fed ad libitum and 12 month-old fed with a caloric restricted diet. Comparisons between young and middle-aged animals in subcutaneous and visceral adipose tissue, and between the 12 month old ad libitum and 12 month old caloric restricted diet in both adipose depots were made.
Project description:Purpose: The goal of this study was the transcriptome high-throughput data analysis of spleen cells from mice infected with a virulent strain of mycobacterium (H37rv) and either fed ad libitum (AL) or caloric restricted (CR) Methods: Spleen cell total RNA profile of 17 weeks old mice (1. MTB infected, Ad libitum fed; 2. MTB infected, Caloric restricted; 3. Not infected, Ad libitum fed; 4. Not infected, Caloric restricted; a pool of 5 animals per group) were generated by deep sequencing, in triplicate, using TruSeq Stranded Total RNA Illumina technology Results: Principal component analysis and unsupervised clustering showed that the RNA-seq profiles of spleen cells from these four groups of mice were clearly distinct and infection was the major force affecting gene expression, with 67% of variance coming from the infection status and another 23% variance being dependent on caloric intake . When directly comparing AL versus CR MTB infected spleens, 628 genes were found differentially expressed. Supervised hierarchical clustering based on the expression of these 628 genes was able to unveil the unique transcriptional profile of CR MTB infected mice compared to both AL MTB infected and Not infected mice. Coclusions: Caloric restriction is able to affect the expression of a significant number of genes in spleen cells isolated from mice infected with MTB. The study of biological process enrichements highlights relevant immune-related regulation in these animals, than may be at the base of the higher capacity of caloric restricted, compared to ad libitum fed, animals to resist MTB infection.
2021-01-08 | GSE127263 | GEO
Project description:Microbiota of caloric restricted mice by 16S
Project description:The SIRT1 deacetylase is one of the best-studied potential mediators of some of the anti-aging effects of calorie restriction (CR); but its role in CR-dependent lifespan extension has not been demonstrated. We previously found that mice lacking both copies of SIRT1 displayed a shorter median lifespan than wild type mice on an ad libitum diet. Here we report that median lifespan extension in CR heterozygote SIRT1+/- mice was identical (51%) to that observed in wild type mice but SIRT1+/- mice displayed a higher frequency of some certain pathologies. Although larger studies in different genetic backgrounds are necessary , these results provide strong initial evidence for the requirement of SIRT1 for the anti-aging effects of CR, but suggest that its high expression is not required for CR-induced lifespan extension. Key words: SIRT1, caloric restriction, lifespan, anti-aging
Project description:Paraffin-embedded lung and spleen tissues analyzed by Eksigent nanoLC-Ultra 2D System and QExactive mass spectrometer. Both lung and spleen tissues were extracted from animals at 4 different conditions (Not infected Ad libitum, Not infected Caloric restricted, Mycobacterium Tuberculosis (MTB) infected Ad libitum, Mycobacterium Tuberculosis (MTB) infected Caloric restricted). Globally, 24 and 23 runs are uploaded for lung and spleen tissues, respectively.
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.
Project description:The experiment aims at a characterization of gene expression changes in duodenum during caloric restriction. The C57BL6 mice were restricted their food intake to 75% of their normal daily portion. The food was delivered daily around 4-6pm for 14 days. The mice were housed with free access to water. The control age-matched mice were fed ad libitum. The publication associated with this dataset concerns WT mice only. However, the experiment and microarray data normalization was performed for samples of WT and PPARgVillinCRE mice together. Thus for analysis reproducibility reasons data of all samples is made available.
Project description:Moderate caloric restriction (CR) and weight loss are beneficial for the promotion of health; however, there is controversy regarding the effects of dieting regimens on behavior. In this study, we investigated two different dieting regimens: repeated fasting and refeeding (RFR) and daily feeding of half the amount of food consumed by RFR mice (CR). Mice in both regimens were subjected to 20% reduction in food intake and transiently reduced their body weights during the first 12 days of the study. Open field, light-dark transition, elevated plus maze, and forced swimming tests indicated that CR, but not RFR, reduced anxiety- and depressive-like behaviors, with a peak on day 8. Using a mouse whole genome microarray, we analyzed gene expression in the prefrontal cortex, amygdala, and hypothalamus. In addition to the caloric restriction-responsive genes commonly modified by RFR and CR, each regimen differentially changed the expression of distinct genes in each region. The most profound change was observed in the amygdala of CR mice: 884 genes were specifically up-regulated. Ingenuity pathway analysis showed that these 884 genes significantly modified 9 canonical pathways in the amygdala. alpha-adrenergic and dopamine receptor signaling were the two top-scoring pathways. Quantitative real-time RT-PCR confirmed the up-regulation of 6 genes in these pathways. Ppp1r1b encoded Darpp-32 including dopamine receptor signaling, and the increased protein was specific for CR mice. Our results suggest that moderate CR may modify anxiety- and depressive-like behaviors and alter gene expression especially in the mouse amygdala. Experiment Overall Design: We tested three feeding regimens. One group of mice had ad libitum (AD) access to food, and was used as a control group. The repeated fasting and refeeding (RFR) group of mice were fasted on day 0 and allowed to feed ad libitum on day 1. Amounts of food consumed by the three mice on day 1 were measured. The half amount of food consumed by the RFR mice was given to three mice in another cage for two days (days 0 and 1) (CR group). The fasting followed by refeeding (RFR) and the restriction of food (CR) were repeated up to day 16. Body weights and consumed chow were measured at 20:00 every day, and then the fasting or feeding period was started. In RFR mice, fasting was started on day 0.Total RNA was prepared from the prefrontal cortex, hypothalamus, and amygdala in the mice of each group on day 8. An equal amount of RNA from 4 mice in each group was pooled and used for microarray analysis.