Project description:Transcriptome analysis using the liver from young versus old mice, fed either normally or under caloric restriction reveals reorganization of distinct circadian signatures related to metabolic aging and nutrient-dependent counterbalance of aging by caloric restriction
Project description:Astrocytes are key cells in brain aging, helping neurons to undertake healthy aging or otherwise letting them enter into a spiral of neurodegeneration. We aimed to characterize astrocytes cultured from senescence-accelerated prone 8 (SAMP8) mice, a mouse model of brain pathological aging, along with the effects of caloric restriction, the most effective rejuvenating treatment known so far. Analysis of the transcriptomic profiles of SAMP8 astrocytes cultured in control conditions and treated with caloric restriction serum was performed using mRNA microarrays. A decrease in mitochondrial and ribosome mRNA, which was restored by caloric restriction, confirmed the age-related profile of SAMP8 astrocytes and the benefits of caloric restriction. An amelioration of antioxidant and neurodegeneration-related path- ways confirmed the brain benefits of caloric restriction. Studies of oxidative stress and mitochondrial function demonstrated a reduction of oxidative damage and partial improvement of mito- chondria after caloric restriction. In summary, caloric restriction showed a significant tendency to normalize pathologically aged astrocytes through the activation of pathways that are protective against the age-related deterioration of brain physiology. Key words: astrocytes; caloric restriction; mitochondria; oxidative stress; RNA microarrays; SAMP8.
Project description:We recruited ten normal-weight healthy men using inclusion criteria as previously described (Collet et al 2017). All males were healthy and not obese or overweight (average age: 23.8 years, average BMI (kg/m2): 23.3). Participants at baseline consumed a balanced diet (50% carbohydrate, 30% fat, and 20% protein). During caloric restriction, volunteers consumed 10% of normal energy requirement (226 kcal/d) for two days, again balanced (50% carbohydrate, 30% fat, and 20% protein), with the same macronutrient composition. After caloric restriction, volunteers were offered three substantial ad libitum buffet meals per day (20 MJ = 4,777 kcal) and additional snacks (16 MJ = 3,821 kcal) between meals for 2 days. They were invited to eat freely until comfortably full; food consumption was covertly measured. We collected fasting plasma samples at 0800 AM at baseline, after CR and refeeding (RF).
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:We used microarray analysis to further our understanding of the mode of action of the well know caloric restriction mimetic rapamycin and the compound Allantoin first studied in the context of aging in this study. His work helps build on our understanding of potential caloric restriction mimetics predicted from our bioinformatic aproach of quering the Connectivity Map, a database of drug-induced gene expression profiles, using the transcriptional profile of CR to identify drugs that induce a similar or opposite gene expression profile. Wild type worms of eat-2 mutants (a model of caloric restriction) were treated with the compounds of study with 2% DMSO or DMSO alone to serve as controls. All samples were peformed in triplicate.
Project description:Comparison of transcriptional profiling in murine hearts obtained from the control mice fed ad libitium (AL) and treated with caloric restriction (CR). Comparison of transcriptional profiling in murine hearts obtained from cardiomyocye-specific Sirt1 knockout mice fed ad libitium and treated with caloric restriction.
