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Differences in genome-wide gene expression response in PBMCs between young and old men upon caloric restriction

ABSTRACT: Caloric restriction (CR) is considered to increase lifespan and to prevent various age-related diseases in different non-human organisms. Only a limited number of CR studies have been performed in humans, and results put CR as a beneficial tool to decrease risk factors in several age-related diseases. The question remains at what age CR should be implemented to be most effective with respect to healthy aging. The aim of our study was to elucidate the role of age in the transcriptional response to a 30% CR diet in immune cells, as immune response is affected during aging. Ten healthy young men, aged 20-34, and nine healthy old men, aged 64-85, were subjected to a two week weight maintenance diet, followed by three weeks of 30% CR. Before and after 30% CR, peripheral blood mononuclear cells’ (PBMCs) whole genome gene expression was assessed. Expression of 554 genes showed a different response between young and old men upon CR. Gene set enrichment analysis revealed a downregulation of gene sets involved in immune response in young men, but not in old men. At baseline, immune response-related genes were already higher expressed in old compared to young men. Upstream regulator analyses revealed that most potential regulators were controlling immune response, and were inhibited in young men upon CR, and activated in old men at baseline. Based on the gene expression data, we conclude that a short period of CR is more effective in young men compared to old men regarding immune related pathways.

ORGANISM(S): Homo sapiens

PROVIDER: GSE63117 | GEO | 2016/10/24

SECONDARY ACCESSION(S): PRJNA266659

REPOSITORIES: GEO

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Differences in genome-wide gene expression response in PBMCs between young and old men upon caloric restriction

Project description:Caloric restriction (CR) is considered to increase lifespan and to prevent various age-related diseases in different non-human organisms. Only a limited number of CR studies have been performed in humans, and results put CR as a beneficial tool to decrease risk factors in several age-related diseases. The question remains at what age CR should be implemented to be most effective with respect to healthy aging. The aim of our study was to elucidate the role of age in the transcriptional response to a 30% CR diet in immune cells, as immune response is affected during aging. Ten healthy young men, aged 20-34, and nine healthy old men, aged 64-85, were subjected to a two week weight maintenance diet, followed by three weeks of 30% CR. Before and after 30% CR, peripheral blood mononuclear cellsâ (PBMCs) whole genome gene expression was assessed. Expression of 554 genes showed a different response between young and old men upon CR. Gene set enrichment analysis revealed a downregulation of gene sets involved in immune response in young men, but not in old men. At baseline, immune response-related genes were already higher expressed in old compared to young men. Upstream regulator analyses revealed that most potential regulators were controlling immune response, and were inhibited in young men upon CR, and activated in old men at baseline. Based on the gene expression data, we conclude that a short period of CR is more effective in young men compared to old men regarding immune related pathways. Gene expression was profiled in peripheral blood mononuclear cells (PBMCs) from young and old men before and after 30% caloric restriction.

2016-10-24 | E-GEOD-63117 | biostudies-arrayexpress

Watanabe2018_State Transition Model with Treatment and Costs

Project description:Model with functions depending on Age, Male, BP (Blood Pressure). There are 3 disease states: Healthy, Sick, and Dead, where the Dead state is terminal. The yearly transition probabilities are: Healthy to Dead: Age/1000; Healthy to Sick: According to function F1 depending on Age and Male and BP; Sick to Healthy: 0.1; Sick to Dead: according to function F2 depending on Age and Male. Pre-Transition Rules: Age increased by 1 and BP by Age/10 each simulation cycle. Post-Transition Rules: Treatment = BP>140 , becomes 1 when BP crosses 140 threshold; BP =BP-Treatment*10 , meaning a drop of 10 once treatment is applied; CostThisYear = Age + \Treatment*10 , cost depends on age and if treatment was taken; Cost= Cost + CostThisYear , it accumulates cost over time. Initial conditions: Healthy = (50 Male, 50 Female with Age =1,2,...,50 for each individual), BP =120, Sick = (0,0) and Dead = (0,0). Output: Number of men and women in each disease state for years 1-10 and their ages and costs in each state. A stratified report by male and female and young – up to age 30 and old above age 30 is produced.

2019-01-30 | MODEL1803120006 | BioModels

Lifelong calorie restriction and markers of colonic health in aging mice

Project description:Diminishment of colonic health is associated with various age-related pathologies. Calorie restriction (CR) is an efficient strategy to increase healthy lifespan, although underlying mechanisms are not fully elucidated. Here we report the effects of lifelong CR on markers of colonic health in aging mice. We show that 30% energy reduction, as compared to a control (C) and moderate-fat (MF) diet, is associated with attenuated immune-related gene expression and lower levels of bile acids in the colon. Pronounced shifts in microbiota composition, together with lowered plasma levels of interleukin 6, in mice exposed to CR are in line with these findings. Furthermore, expression of genes involved in lipid metabolism was higher upon CR as compared to C and MF, pointing towards efficient regulation of energy metabolism. Switching from CR to an ad libitum MF diet at old age revealed remarkable phenotypic plasticity, although expression of a small subset of genes remained CR-associated. This research demonstrates that CR beneficially affects markers of colonic health in aging mice and as such may attenuate the progressive age-related decline in health.

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Age-Dependent Changes in the Plasma Proteome of Healthy Adults

Project description:Human blood plasma is a complex which communicates with most parts of the body and reflects changes in the state of the organism, therefore identifying age-related biomarkers can help to predict and monitor age-related physiological decline and diseases, as well as to find new treatments for diseases. In this study, TMT-LC-MS/MS was utilized to screen for the differentially expressed plasma proteins in 118 healthy adults with different ages. Participants were divided into three groups: 21-30 (Young), 41-50 (Middle) and ≥60 (Old), the number of differentially expressed proteins when Young vs Middle, Middle vs Old and Young vs Old were 82, 22 and 99, respectively. These proteins were found to be involved in numerous physiological processes such as “negative regulation of smooth muscle cell proliferation” and “blood coagulation”. Meanwhile when Young vs Middle or Old, “Complement and coagulation cascades” was confirmed the top enriched pathway by KEGG pathway enrichment analysis. Functional phenotyping of the proteome demonstrated that the plasma proteomic profiles of Young adults were strikingly dissimilar to the Middle or Old adults. The results of this study mapped the variation in expression of plasma proteins, and provided information about possible biomarkers/treatments for different kinds of age-related function disorders.

2020-10-19 | PXD016199 | Pride

Effects of sex and age on skeletal muscle gene expression in normal men and women

Project description:Muscle biopsies taken from vastus lateralis muscle of 15 men and 15 women after 3 days of standardized diet and activity to examine effects of sex and age Subjects were either young adults (7 men and 7 women, 20-29 yr old) or older (8 men and 8 women, 65-75 yr old) Affymetrix U133A and U133B arrays were scanned both before (S1) and after (S2) antibody enhancement. This file has U133A S1 data. Effects of age were computed for men and women separately with an alternative method previously and data submitted as GSE362 (men) and GSE674 (women). Keywords: sex differences, age-related differences

2007-11-24 | GSE9676 | GEO

Expression data from SIRT6 knockout, young WT and old WT mice brains

Project description:Brain-specific SIRT6-KO mice present increased DNA damage, learning impairments, and neurodegenerative phenotypes, placing SIRT6 as a key protein in preventing neurodegeneration. In the aging brain, SIRT6 levels/activity decline, which is accentuated in Alzheimer's patients. To understand SIRT6 roles in transcript pattern changes, we analyzed transcriptomes of young WT, old WT and young SIRT6-KO mice brains, and found changes in gene expression related to healthy and pathological aging. In addition, we traced these differences in human and mouse samples of Alzheimer's and Parkinson's diseases, healthy aging and calorie restriction (CR). Our results define four gene expression categories that change with age in a pathological or non-pathological manner, which are either reversed or not by CR. We found that each of these gene expression categories is associated with specific transcription factors, thus serving as potential candidates for their category-specific regulation. One of these candidates is YY1, which we found to act together with SIRT6 regulating specific processes. We thus argue that SIRT6 has a pivotal role in preventing age-related transcriptional changes in brains. Therefore, reduced SIRT6 activity may drive pathological age-related gene expression signatures in the brain.

2021-06-18 | GSE178432 | GEO

Transcription profiling of mouse heart, brain, and skeletal muscle to determine the rffect of age, calorie restriction and resveratrol on gene expression

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

Expression data from skeletal muscle of young, old and old calorie restricted mice

Project description:We investigated age-related changes in the transcriptional profile of skeletal muscle in 5 month old (young) and 25 month old (old) C57BL/6NHsd mice using high density oligonucleotide arrays (22,690 transcripts probed). We identified 712 transcripts that are differentially expressed in young (5 month old) and old (25-month old) mouse skeletal muscle. Caloric restriction (CR) completely or partially reversed 87% of the changes in expression. Examination of individual genes revealed a transcriptional profile indicative of increased p53 activity in the older muscle. To determine whether the increase in p53 activity is associated with transcriptional activation of apoptotic targets, we performed RT-PCR on four well known mediators of p53-induced apoptosis: puma, noxa, tnfrsf10b and bok. Expression levels for these proapoptotic genes increased significantly with age (P<0.05), while CR significantly lowered expression levels for these genes as compared to control fed old mice (P<0.05). Age-related induction of p53-related genes was observed in multiple tissues, but was not observed in SOD2+/- and GPX4+/- mice, suggesting that oxidative stress does not mediate the observed age-related increase in expression. Western blot analysis confirmed that protein levels for both p21 and GADD45a, two established transcriptional targets of p53, were higher in the older muscle tissue. These observations support a role for p53-mediated apoptotic activity in mammalian aging. Keywords: aging, calorie restriction, muscle, p53

2006-12-01 | GSE6323 | GEO

Postprandial Metabolism is Impaired in Overweight Normoglycemic Young Adults without Family History of Diabetes

Project description:<p>While the risk factors for Type 2 diabetes (T2DM) are known, early predictive markers of transition from normal to a prediabetes state are unidentified. We studied the basal metabolism and metabolic response to a mixed-meal challenge in 110 healthy subjects in the age group of 18 to 40 years (Male:Female = 1:1); grouped into first degree relatives of patients with T2DM (n = 30), those with a body mass index >23 kg/m2 but <30 kg/m2 (n = 30), those with prediabetes (n = 20) and normal controls (n = 30). We performed an untargeted metabolomics analysis of plasma and related that with clinical and biochemical parameters, markers of inflammation, and insulin sensitivity. Similar to prediabetes subjects, overweight subjects had insulin resistance and significantly elevated levels of C-peptide, adiponectin and glucagon and lower level of ghrelin. Metabolites such as MG(22:2(13Z, 16Z)/0:0/0:0) and LysoPC (15:0) were reduced in overweight and prediabetes subjects. Insulin sensitivity was significantly lower in men. Fasting levels of uric acid, xanthine, and glycochenodeoxycholic-3-glucuronide were elevated in men. However, both lysophospholipids and antioxidant defense metabolites were higher in women. Impaired postprandial metabolism and insulin sensitivity in overweight normoglycemic young adults indicates a risk of developing hyperglycemia. Our results also indicate a higher risk of diabetes in young men.</p>

2019-03-14 | MTBLS743 | MetaboLights

Transcription profiling of human muscle biopises after standard diet and activity regimes

Project description:Muscle biopsies taken from vastus lateralis muscle of 15 men and 15 women after 3 days of standardized diet and activity to examine effects of sex and age; Subjects were either young adults (7 men and 7 women, 20-29 yr old) or older (8 men and 8 women, 65-75 yr old); Affymetrix U133A and U133B arrays were scanned both before (S1) and after (S2) antibody enhancement. This file has U133A S1 data. Effects of age were computed for men and women separately with an alternative method previously and data submitted as GSE362 (men) and GSE674 (women). Experiment Overall Design: Gene expressions profiles were generated for each individual for a total of 30 profiles (15 male, 15 female, 14 younger, 16 older)

2008-06-17 | E-GEOD-9676 | biostudies-arrayexpress

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