scholarly journals Iron supplementation delays aging and extends cellular lifespan through potentiation of mitochondrial function

2021 ◽  
Author(s):  
Jovian Lin Jing ◽  
Trishia Cheng Yi Ning ◽  
Federica Natali ◽  
Frank Eisenhaber ◽  
Mohammad Alfatah
Keyword(s):  
Gene Expression ◽  
Iron Supplementation ◽  
Energy Homeostasis ◽  
Expression Profiles ◽  
Model Organism ◽  
Tca Cycle ◽  
Knockout Mutant ◽  
Age Related ◽  
Mitochondrial Functions ◽  
Metabolic Activities

Abstract Aging is the greatest challenge of humankind worldwide. Aging is associated with a progressive loss of physiological integrity due to a decline in cellular metabolism and functions. Such metabolic changes lead to age-related diseases, thereby compromising human health for the remaining life. Thus, there is an urgent need to identify geroprotectors that regulate metabolic functions to target the aging biological processes. Nutrients are the major regulator of metabolic activities to coordinate cell growth and development. Iron is an important nutrient involved in several biological functions, including metabolism. In this study, using yeast as an aging model organism, we show that iron supplementation delays aging and increases the cellular lifespan. To determine how iron supplementation increases the lifespan, we performed the gene expression analysis of mitochondria, the main cellular hub of iron utilization. Quantitative analysis of gene expression data reveals that iron supplementation upregulates the expression of mitochondrial tricarboxylic acid (TCA) cycle and electron transport chain (ETC) genes. Furthermore, in agreement with expression profiles of mitochondrial genes, ATP level is elevated by iron supplementation, which is required for increasing the cellular lifespan. To confirm, we tested the role of iron supplementation in the AMPK knockout mutant. AMPK is a highly conserved controller of mitochondrial metabolism and energy homeostasis. Remarkably, iron supplementation rescued the short lifespan of AMPK knockout mutant confirmed the anti-aging role through enhancement of mitochondrial functions. Thus our results suggest a potential therapeutic use of iron supplementation to delay aging and prolong healthspan.

scholarly journals Age-related differences in monocyte DNA methylation and immune function in healthy Kenyan adults and children

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Katherine R. Dobbs ◽  
Paula Embury ◽  
Emmily Koech ◽  
Sidney Ogolla ◽  
Stephen Munga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Young Adults ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Innate Immune ◽  
Inflammatory Gene Expression ◽  
Cpg Sites ◽  
Age Related ◽  
Adults And Children

Abstract Background Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profiles in monocytes from young adults and children from western Kenya. Results We identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles. Conclusions These findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions.

Age-related changes in the transcriptional profile of mouse RPE/choroid

2003 ◽  
Vol 15 (3) ◽  
pp. 258-262 ◽  
Author(s):  
Hisashi Ida ◽  
Sharon A. Boylan ◽  
Andrea L. Weigel ◽  
Leonard M. Hjelmeland
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Cdna Probe ◽  
Gene Expression Profiles ◽  
Age Related Macular Degeneration ◽  
Pcr Analysis ◽  
Rt Pcr ◽  
Mouse Cdna ◽  
Age Related ◽  
Age Related Changes

To evaluate the age-related changes in gene expression occurring in the complex of retinal pigmented epithelium, Bruch’s membrane, and choroid (RPE/choroid), we examined the gene expression profiles of young adult (2 mo) and old (24 mo) male C57BL/6 mice. cDNA probe sets from individual animals were synthesized using total RNA isolated from the RPE/choroid of each animal. Probes were amplified using the Clontech SMART system, radioactively labeled, and hybridized to two different Clontech Atlas mouse cDNA arrays. From each age group, three independent triplicates were hybridized to the arrays. Statistical analyses were performed using the Significance Analysis of Microarrays program (SAM version 1.13; Stanford University). Selected array results were confirmed by semi-quantitative RT-PCR analysis. Of 2,340 genes represented on the arrays, ∼60% were expressed in young and/or old mouse RPE/choroid. A moderate fraction (12%) of all expressed genes exhibited a statistically significant change in expression with age. Of these 150 genes, all but two, HMG14 and carboxypeptidase E, were upregulated with age. Many of these upregulated genes can be grouped into several broad functional categories: immune response, proteases and protease inhibitors, stress response, and neovascularization. RT-PCR results from six of six genes examined confirmed the differential change in expression with age of these genes. Our study provides likely candidate genes to further study their role in the development of age-related macular degeneration and other aging diseases affecting the RPE/choroid.

EFFECTIVE MODELS FOR GENE NETWORKS AND THEIR APPLICATIONS

2012 ◽  
Vol 07 (01n02) ◽  
pp. 41-70 ◽  
Author(s):  
JASON SHULMAN ◽  
LARS SEEMANN ◽  
GREGG W. ROMAN ◽  
GEMUNU H. GUNARATNE
Keyword(s):  
Gene Expression ◽  
Gene Networks ◽  
Gene Network ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Stationary Solutions ◽  
The State ◽  
Effective Model ◽  
Knockout Mutant ◽  
Double Knockout

Networks are used to abstract large, highly-coupled sets of objects. Their analyses have included network classification into a few broad classes and selection of small substructures that perform simple yet common tasks. One issue that has received little attention is how the state of a network can be moved according to a pre-specified set of guidelines. In this paper, we address this question in the context of gene networks. In general, neither the full membership of the gene network associated with a biological process nor the precise form of interactions between nodes is known. What is available, through microarrays or sequencing, are gene expression profiles of an organism or its viable mutants. Our approach relies only on these expression profiles, and not on the availability of an accurate model for the network. The first step is to select a small set of core- or master- nodes, such as transcription factors or microRNAs, that can be used to alter the levels of many of the remaining genes in the network. We ask how the state — or solution — of the gene network changes as the levels of these master nodes are altered externally. The object of our study is, not the network, but the surface of these solutions. We argue that it can be approximated using gene expression profiles of the organism and single manipulation of master node activity. This is done through an "effective model." The effective model as well as error estimates for its predictions can be derived from experimental data. The method is validated using synthetic gene networks that have stationary solutions and those that are periodically driven, e.g., circadian networks. An effective model for the oxygen-deprivation network of E.coli is constructed using previously published gene expression profiles, and used to predict the expression levels in a double knockout mutant. Less that 30% of the predictions lie outside the 5% confidence level. We propose the use of the effective model methodology to compute how Drosophila melanogaster in the normal state can be genetically altered into a pre-defined sleep deprived-like state.

scholarly journals Adipose gene expression profiles reveal novel insights into the adaptation of northern Eurasian semi-domestic reindeer (Rangifer tarandus)

2021 ◽  
Author(s):  
Melak Weldenegodguad ◽  
Kisun Pokharel ◽  
Laura Niiranen ◽  
Päivi Soppela ◽  
Innokentyi Ammosov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Energy Metabolism ◽  
Energy Homeostasis ◽  
Rangifer Tarandus ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Northern Eurasia ◽  
Adipose Tissues ◽  
Arctic Conditions

AbstractReindeer (Rangifer tarandus) are semi-domesticated animals adapted to the challenging arctic conditions of northern Eurasia. Adipose tissues play a crucial role in animals living in northern environments by altering gene expression in their tissues to regulate energy homeostasis and thermogenic activity. Here, we performed transcriptome profiling by RNA sequencing of adipose tissues from three different anatomical depots: metacarpal (bone marrow), perirenal, and prescapular fat in Finnish and Even reindeer (in Sakha) during two seasonal time points (spring and winter). On average 36.5 million pair-ended clean reads were obtained for each sample, and a total of 16,362 genes were expressed in our data. Gene expression profiles in metacarpal tissue were distinct and clustered separately from perirenal and prescapular adipose tissues. Notably, metacarpal adipose tissue appeared to have a significant role in the regulation of the energy metabolism of reindeer in spring when their nutritional condition is poor after winter. During spring, when the animals are in less optimal condition, genes associated with the immune system (e.g., CCL2, CCL11, CXCL14, IGSF3, IGHM, IGLC7, IGKC, JCHAIN, and IGSF10) were upregulated in the perirenal and prescapular adipose tissue, while genes involved in energy metabolism (e.g., ACOT2, APOA1, ANGPTL1, ANGPTL8, ELOVL7, MSMO1, PFKFB1, and ST3GAL6) were upregulated in metacarpal tissue. Even reindeer harboured relatively fewer significantly differentially expressed genes than Finnish reindeer, irrespective of the season, possibly owing to climatic and management differences. Moreover, blood and tissue parameters reflecting general physiological and metabolic status showed less seasonal variation in Even reindeer than in Finnish reindeer. This study identified adipose candidate genes potentially involved in immune response, fat deposition, energy metabolism, development, cell growth, and organogenesis. Taken together, this study provides new information on the mechanisms by which reindeer adapt to less optimal arctic conditions.

scholarly journals Social boldness correlates with brain gene expression in male green anoles

2021 ◽  
Author(s):  
David Kabelik ◽  
Allison R. Julien ◽  
Dave Ramirez ◽  
Lauren A. O’Connell
Keyword(s):  
Gene Expression ◽  
Social Behavior ◽  
Expression Profiles ◽  
Coping Styles ◽  
Model Organism ◽  
Gene Expression Profiles ◽  
Ventromedial Hypothalamus ◽  
Group Differences ◽  
Significant Group ◽  
Neural Underpinnings

AbstractWithin populations, some individuals tend to exhibit a bold or shy social behavior phenotype relative to the mean. The neural underpinnings of these differing phenotypes – also described as syndromes, personalities, and coping styles – is an area of ongoing investigation. Although a social decision-making network has been described across vertebrate taxa, most studies examining activity within this network do so in relation to exhibited differences in behavioral expression. Our study instead focuses on constitutive gene expression in bold and shy individuals by isolating baseline gene expression profiles that influence social boldness predisposition, rather than those reflecting the results of social interaction and behavioral execution. We performed this study on male green anole lizards (Anolis carolinensis), an established model organism for behavioral research, which provides a crucial comparison group to investigations of birds and mammals. After identifying subjects as bold or shy through repeated reproductive and agonistic behavior testing, we used RNA sequencing to compare gene expression profiles between these groups within various forebrain, midbrain, and hindbrain regions. The ventromedial hypothalamus had the largest group differences in gene expression, with bold males having increased expression of calcium channels and neuroendocrine receptor genes compared to shy males. Conversely, shy males express more integrin alpha-10 in the majority of examined regions. There were no significant group differences in physiology or hormone levels. Our results highlight the ventromedial hypothalamus as an important center of behavioral differences across individuals and provide novel candidates for investigation into the regulation of individual variation in social behavior phenotype.

scholarly journals ANISEED 2019: 4D exploration of genetic data for an extended range of tunicates

2019 ◽  
Author(s):  
Justine Dardaillon ◽  
Delphine Dauga ◽  
Paul Simion ◽  
Emmanuel Faure ◽  
Takeshi A Onuma ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Model Organism ◽  
Gene Expression Profiles ◽  
Sister Group ◽  
Model Organism Database ◽  
Oikopleura Dioica ◽  
Genetic Features ◽  
Taxonomic Range ◽  
Or Gene

Abstract ANISEED (https://www.aniseed.cnrs.fr) is the main model organism database for the worldwide community of scientists working on tunicates, the vertebrate sister-group. Information provided for each species includes functionally-annotated gene and transcript models with orthology relationships within tunicates, and with echinoderms, cephalochordates and vertebrates. Beyond genes the system describes other genetic elements, including repeated elements and cis-regulatory modules. Gene expression profiles for several thousand genes are formalized in both wild-type and experimentally-manipulated conditions, using formal anatomical ontologies. These data can be explored through three complementary types of browsers, each offering a different view-point. A developmental browser summarizes the information in a gene- or territory-centric manner. Advanced genomic browsers integrate the genetic features surrounding genes or gene sets within a species. A Genomicus synteny browser explores the conservation of local gene order across deuterostome. This new release covers an extended taxonomic range of 14 species, including for the first time a non-ascidian species, the appendicularian Oikopleura dioica. Functional annotations, provided for each species, were enhanced through a combination of manual curation of gene models and the development of an improved orthology detection pipeline. Finally, gene expression profiles and anatomical territories can be explored in 4D online through the newly developed Morphonet morphogenetic browser.

Global Analysis of Age-Related Expression Profiles of Mouse Liver Genes: Toward Understanding Age-Related Homeostasis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3938-3938
Author(s):  
Sumiko Kurachi ◽  
Emi Suenaga ◽  
Kotoku Kurachi
Keyword(s):  
Gene Expression ◽  
Mouse Liver ◽  
Expression Profiles ◽  
Global Analysis ◽  
Expression Patterns ◽  
Regulatory Protein ◽  
Regulatory Mechanisms ◽  
Gene Group ◽  
Age Related ◽  
Microarray Analyses

Abstract For understanding aging as well as various age-related diseases, it is critical to establish the basic regulatory mechanisms underlying age-related homeostatsis. Through systematic analyses of transgenic mice carrying factor IX and protein C genes, we recently discovered the first molecular mechanism of age-related homeostasis, ASE/AIE-mediated age-related regulatory mechanism of gene expression (Kurachi et. al., Science 1999; Zhang et. al., J. Biol. Chem. 2002; J. Thromb. Haemost. 2005). This laid the foundation for further studies toward an integrated understanding of age-related homeostasis. Here we report global analyses of age-related expression profiles of mouse liver genes. For quantification of expression levels of liver genes of mice at 1, 3, 6, 12, 18 and 24 month of age, Affymetrix GeneChip® Mouse Expression Array 430A (MOE430A with 23,643 probes) were used. These microarray analyses detected 9148 probes as qualified meaningful and the data were subjected to extensive analyses by GeneSpring and IPA network analysis softwares. Real time PCR analyses of representative genes were performed for verifying excellent reproducibility of age-related expression profiles determined by microarray analyses. Age-related stages, particularly of puberty and aging, were identified as the major phases for age-related changes in gene expression. Strong relationships between expression level and ontology, indicating that the highest expression gene group, next highest expression group and lowest level expression gene group are of secreted proteins, mitochondoreal proteins and nuclear regulatory protein, respectively. Most importantly, we successfully identified about a dozen unique and fundamental age-related gene expression patterns including those of age-related stable, gradual increase or decrease, and aging-related dramatic increase or decrease types of expression. These findings led us to a new hypothesis that complex and dynamic age-related regulations of genes are produced by a relatively small number of fundamental regulatory mechanisms. These mechanisms may function independently or in various combinations, thus explaining an essential feature of age-related homeostasis.

Metabolic and transcriptional patterns accompanying glutamine depletion and repletion in mouse hepatoma cells: a model for physiological regulatory networks

2004 ◽  
Vol 16 (2) ◽  
pp. 247-255 ◽  
Author(s):  
Matthew S. Wong ◽  
R. Michael Raab ◽  
Isidore Rigoutsos ◽  
Gregory N. Stephanopoulos ◽  
Joanne K. Kelleher
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Dna Microarrays ◽  
Cell Function ◽  
De Novo ◽  
Expression Profiles ◽  
Mammalian Cell Culture ◽  
Gene Expression Profiles ◽  
Tca Cycle ◽  
Glycolytic Flux

An important objective in postgenomic biology is to link gene expression to function by developing physiological networks that include data from the genomic and functional levels. Here, we develop a model for the analysis of time-dependent changes in metabolites, fluxes, and gene expression in a hepatic model system. The experimental framework chosen was modulation of extracellular glutamine in confluent cultures of mouse Hepa1-6 cells. The importance of glutamine has been demonstrated previously in mammalian cell culture by precipitating metabolic shifts with glutamine depletion and repletion. Our protocol removed glutamine from the medium for 24 h and returned it for a second 24 h. Flux assays of glycolysis, the tricarboxylic acid (TCA) cycle, and lipogenesis were used at specified intervals. All of these fluxes declined in the absence of glutamine and were restored when glutamine was repleted. Isotopomer spectral analysis identified glucose and glutamine as equal sources of lipogenic carbon. Metabolite measurements of organic acids and amino acids indicated that most metabolites changed in parallel with the fluxes. Experiments with actinomycin D indicated that de novo mRNA synthesis was required for observed flux changes during the depletion/repletion of glutamine. Analysis of gene expression data from DNA microarrays revealed that many more genes were anticorrelated with the glycolytic flux and glutamine level than were correlated with these indicators. In conclusion, this model may be useful as a prototype physiological regulatory network where gene expression profiles are analyzed in concert with changes in cell function.

scholarly journals Age-Related Modulation of the Effects of Obesity on Gene Expression Profiles of Mouse Bone Marrow and Epididymal Adipocytes

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e72367 ◽  
Author(s):  
Li-Fen Liu ◽  
Wen-Jun Shen ◽  
Masami Ueno ◽  
Shailja Patel ◽  
Salman Azhar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Mouse Bone Marrow ◽  
Age Related

scholarly journals The Role of MicroRNAs in Mitochondria-Mediated Eye Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Sabrina Carrella ◽  
Filomena Massa ◽  
Alessia Indrieri
Keyword(s):  
Current Knowledge ◽  
Expression Profiles ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
High Energy ◽  
Light Signal ◽  
Eye Diseases ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Mitochondrial Functions

The retina is among the most metabolically active tissues with high-energy demands. The peculiar distribution of mitochondria in cells of retinal layers is necessary to assure the appropriate energy supply for the transmission of the light signal. Photoreceptor cells (PRs), retinal pigment epithelium (RPE), and retinal ganglion cells (RGCs) present a great concentration of mitochondria, which makes them particularly sensitive to mitochondrial dysfunction. To date, visual loss has been extensively correlated to defective mitochondrial functions. Many mitochondrial diseases (MDs) show indeed neuro-ophthalmic manifestations, including retinal and optic nerve phenotypes. Moreover, abnormal mitochondrial functions are frequently found in the most common retinal pathologies, i.e., glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR), that share clinical similarities with the hereditary primary MDs. MicroRNAs (miRNAs) are established as key regulators of several developmental, physiological, and pathological processes. Dysregulated miRNA expression profiles in retinal degeneration models and in patients underline the potentiality of miRNA modulation as a possible gene/mutation-independent strategy in retinal diseases and highlight their promising role as disease predictive or prognostic biomarkers. In this review, we will summarize the current knowledge about the participation of miRNAs in both rare and common mitochondria-mediated eye diseases. Definitely, given the involvement of miRNAs in retina pathologies and therapy as well as their use as molecular biomarkers, they represent a determining target for clinical applications.

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