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Sample records for ageing model podospora

  1. A Genome-Wide Longitudinal Transcriptome Analysis of the Aging Model Podospora anserine

    PubMed Central

    Philipp, Oliver; Hamann, Andrea; Servos, Jörg; Werner, Alexandra; Koch, Ina; Osiewacz, Heinz D.

    2013-01-01

    Aging of biological systems is controlled by various processes which have a potential impact on gene expression. Here we report a genome-wide transcriptome analysis of the fungal aging model Podospora anserina. Total RNA of three individuals of defined age were pooled and analyzed by SuperSAGE (serial analysis of gene expression). A bioinformatics analysis identified different molecular pathways to be affected during aging. While the abundance of transcripts linked to ribosomes and to the proteasome quality control system were found to decrease during aging, those associated with autophagy increase, suggesting that autophagy may act as a compensatory quality control pathway. Transcript profiles associated with the energy metabolism including mitochondrial functions were identified to fluctuate during aging. Comparison of wild-type transcripts, which are continuously down-regulated during aging, with those down-regulated in the long-lived, copper-uptake mutant grisea, validated the relevance of age-related changes in cellular copper metabolism. Overall, we (i) present a unique age-related data set of a longitudinal study of the experimental aging model P. anserina which represents a reference resource for future investigations in a variety of organisms, (ii) suggest autophagy to be a key quality control pathway that becomes active once other pathways fail, and (iii) present testable predictions for subsequent experimental investigations. PMID:24376646

  2. Enzymatic synthesis of model substrates recognized by glucuronoyl esterases from Podospora anserina and Myceliophthora thermophila.

    PubMed

    Katsimpouras, Constantinos; Bénarouche, Anaïs; Navarro, David; Karpusas, Michael; Dimarogona, Maria; Berrin, Jean-Guy; Christakopoulos, Paul; Topakas, Evangelos

    2014-06-01

    Glucuronoyl esterases (GEs) are recently discovered enzymes that are suggested to cleave the ester bond between lignin alcohols and xylan-bound 4-O-methyl-D-glucuronic acid. Although their potential use for enhanced enzymatic biomass degradation and synthesis of valuable chemicals renders them attractive research targets for biotechnological applications, the difficulty to purify natural fractions of lignin-carbohydrate complexes hampers the characterization of fungal GEs. In this work, we report the synthesis of three aryl alkyl or alkenyl D-glucuronate esters using lipase B from Candida antarctica (CALB) and their use to determine the kinetic parameters of two GEs, StGE2 from the thermophilic fungus Myceliophthora thermophila (syn. Sporotrichum thermophile) and PaGE1 from the coprophilous fungus Podospora anserina. PaGE1 was functionally expressed in the methylotrophic yeast Pichia pastoris under the transcriptional control of the alcohol oxidase (AOX1) promoter and purified to its homogeneity (63 kDa). The three D-glucuronate esters contain an aromatic UV-absorbing phenol group that facilitates the quantification of their enzymatic hydrolysis by HPLC. Both enzymes were able to hydrolyze the synthetic esters with a pronounced preference towards the cinnamyl-D-glucuronate ester. The experimental results were corroborated by computational docking of the synthesized substrate analogues. We show that the nature of the alcohol portion of the hydrolyzed ester influences the catalytic efficiency of the two GEs. PMID:24531271

  3. Plant biomass degrading ability of the coprophilic ascomycete fungus Podospora anserina.

    PubMed

    Couturier, Marie; Tangthirasunun, Narumon; Ning, Xie; Brun, Sylvain; Gautier, Valérie; Bennati-Granier, Chloé; Silar, Philippe; Berrin, Jean-Guy

    2016-01-01

    The degradation of plant biomass is a major challenge towards the production of bio-based compounds and materials. As key lignocellulolytic enzyme producers, filamentous fungi represent a promising reservoir to tackle this challenge. Among them, the coprophilous ascomycete Podospora anserina has been used as a model organism to study various biological mechanisms because its genetics are well understood and controlled. In 2008, the sequencing of its genome revealed a great diversity of enzymes targeting plant carbohydrates and lignin. Since then, a large array of lignocellulose-acting enzymes has been characterized and genetic analyses have enabled the understanding of P. anserina metabolism and development on plant biomass. Overall, these research efforts shed light on P. anserina strategy to unlock recalcitrant lignocellulose deconstruction. PMID:27263000

  4. Peroxisome dynamics during development of the fungus Podospora anserina.

    PubMed

    Takano-Rojas, Harumi; Zickler, Denise; Peraza-Reyes, Leonardo

    2016-01-01

    Peroxisomes are versatile and dynamic organelles that are required for the development of diverse eukaryotic organisms. We demonstrated previously that in the fungus Podospora anserina different peroxisomal functions are required at distinct stages of sexual development, including the initiation and progression of meiocyte (ascus) development and the differentiation and germination of sexual spores (ascospores). Peroxisome assembly during these processes relies on the differential activity of the protein machinery that drives the import of proteins into the organelle, indicating a complex developmental regulation of peroxisome formation and activity. Here we demonstrate that peroxisome dynamics is also highly regulated during development. We show that peroxisomes in P. anserina are highly dynamic and respond to metabolic and environmental cues by undergoing changes in size, morphology and number. In addition, peroxisomes of vegetative and sexual cell types are structurally different. During sexual development peroxisome number increases at two stages: at early ascus differentiation and during ascospore formation. These processes are accompanied by changes in peroxisome structure and distribution, which include a cell-polarized concentration of peroxisomes at the beginning of ascus development, as well as a morphological transition from predominantly spherical to elongated shapes at the end of the first meiotic division. Further, the mostly tubular peroxisomes present from second meiotic division to early ascospore formation again become rounded during ascospore differentiation. Ultimately the number of peroxisomes dramatically decreases upon ascospore maturation. Our results reveal a precise regulation of peroxisome dynamics during sexual development and suggest that peroxisome constitution and function during development is defined by the coordinated regulation of the proteins that control peroxisome assembly and dynamics. PMID:26908647

  5. Structure and Biophysical Characterization of the S-Adenosylmethionine-dependent O-Methyltransferase PaMTH1, a Putative Enzyme Accumulating during Senescence of Podospora anserina.

    PubMed

    Chatterjee, Deep; Kudlinzki, Denis; Linhard, Verena; Saxena, Krishna; Schieborr, Ulrich; Gande, Santosh L; Wurm, Jan Philip; Wöhnert, Jens; Abele, Rupert; Rogov, Vladimir V; Dötsch, Volker; Osiewacz, Heinz D; Sreeramulu, Sridhar; Schwalbe, Harald

    2015-06-26

    Low levels of reactive oxygen species (ROS) act as important signaling molecules, but in excess they can damage biomolecules. ROS regulation is therefore of key importance. Several polyphenols in general and flavonoids in particular have the potential to generate hydroxyl radicals, the most hazardous among all ROS. However, the generation of a hydroxyl radical and subsequent ROS formation can be prevented by methylation of the hydroxyl group of the flavonoids. O-Methylation is performed by O-methyltransferases, members of the S-adenosyl-l-methionine (SAM)-dependent O-methyltransferase superfamily involved in the secondary metabolism of many species across all kingdoms. In the filamentous fungus Podospora anserina, a well established aging model, the O-methyltransferase (PaMTH1) was reported to accumulate in total and mitochondrial protein extracts during aging. In vitro functional studies revealed flavonoids and in particular myricetin as its potential substrate. The molecular architecture of PaMTH1 and the mechanism of the methyl transfer reaction remain unknown. Here, we report the crystal structures of PaMTH1 apoenzyme, PaMTH1-SAM (co-factor), and PaMTH1-S-adenosyl homocysteine (by-product) co-complexes refined to 2.0, 1.9, and 1.9 Å, respectively. PaMTH1 forms a tight dimer through swapping of the N termini. Each monomer adopts the Rossmann fold typical for many SAM-binding methyltransferases. Structural comparisons between different O-methyltransferases reveal a strikingly similar co-factor binding pocket but differences in the substrate binding pocket, indicating specific molecular determinants required for substrate selection. Furthermore, using NMR, mass spectrometry, and site-directed active site mutagenesis, we show that PaMTH1 catalyzes the transfer of the methyl group from SAM to one hydroxyl group of the myricetin in a cation-dependent manner. PMID:25979334

  6. Structure and Biophysical Characterization of the S-Adenosylmethionine-dependent O-Methyltransferase PaMTH1, a Putative Enzyme Accumulating during Senescence of Podospora anserina *

    PubMed Central

    Chatterjee, Deep; Kudlinzki, Denis; Linhard, Verena; Saxena, Krishna; Schieborr, Ulrich; Gande, Santosh L.; Wurm, Jan Philip; Wöhnert, Jens; Abele, Rupert; Rogov, Vladimir V.; Dötsch, Volker; Osiewacz, Heinz D.; Sreeramulu, Sridhar; Schwalbe, Harald

    2015-01-01

    Low levels of reactive oxygen species (ROS) act as important signaling molecules, but in excess they can damage biomolecules. ROS regulation is therefore of key importance. Several polyphenols in general and flavonoids in particular have the potential to generate hydroxyl radicals, the most hazardous among all ROS. However, the generation of a hydroxyl radical and subsequent ROS formation can be prevented by methylation of the hydroxyl group of the flavonoids. O-Methylation is performed by O-methyltransferases, members of the S-adenosyl-l-methionine (SAM)-dependent O-methyltransferase superfamily involved in the secondary metabolism of many species across all kingdoms. In the filamentous fungus Podospora anserina, a well established aging model, the O-methyltransferase (PaMTH1) was reported to accumulate in total and mitochondrial protein extracts during aging. In vitro functional studies revealed flavonoids and in particular myricetin as its potential substrate. The molecular architecture of PaMTH1 and the mechanism of the methyl transfer reaction remain unknown. Here, we report the crystal structures of PaMTH1 apoenzyme, PaMTH1-SAM (co-factor), and PaMTH1-S-adenosyl homocysteine (by-product) co-complexes refined to 2.0, 1.9, and 1.9 Å, respectively. PaMTH1 forms a tight dimer through swapping of the N termini. Each monomer adopts the Rossmann fold typical for many SAM-binding methyltransferases. Structural comparisons between different O-methyltransferases reveal a strikingly similar co-factor binding pocket but differences in the substrate binding pocket, indicating specific molecular determinants required for substrate selection. Furthermore, using NMR, mass spectrometry, and site-directed active site mutagenesis, we show that PaMTH1 catalyzes the transfer of the methyl group from SAM to one hydroxyl group of the myricetin in a cation-dependent manner. PMID:25979334

  7. Insights into Exo- and Endoglucanase Activities of Family 6 Glycoside Hydrolases from Podospora anserina

    PubMed Central

    Poidevin, Laetitia; Feliu, Julia; Doan, Annick; Berrin, Jean-Guy; Bey, Mathieu; Coutinho, Pedro M.; Henrissat, Bernard; Record, Eric

    2013-01-01

    The ascomycete Podospora anserina is a coprophilous fungus that grows at late stages on droppings of herbivores. Its genome encodes a large diversity of carbohydrate-active enzymes. Among them, four genes encode glycoside hydrolases from family 6 (GH6), the members of which comprise putative endoglucanases and exoglucanases, some of them exerting important functions for biomass degradation in fungi. Therefore, this family was selected for functional analysis. Three of the enzymes, P. anserina Cel6A (PaCel6A), PaCel6B, and PaCel6C, were functionally expressed in the yeast Pichia pastoris. All three GH6 enzymes hydrolyzed crystalline and amorphous cellulose but were inactive on hydroxyethyl cellulose, mannan, galactomannan, xyloglucan, arabinoxylan, arabinan, xylan, and pectin. PaCel6A had a catalytic efficiency on cellotetraose comparable to that of Trichoderma reesei Cel6A (TrCel6A), but PaCel6B and PaCel6C were clearly less efficient. PaCel6A was the enzyme with the highest stability at 45°C, while PaCel6C was the least stable enzyme, losing more than 50% of its activity after incubation at temperatures above 30°C for 24 h. In contrast to TrCel6A, all three studied P. anserina GH6 cellulases were stable over a wide range of pHs and conserved high activity at pH values of up to 9. Each enzyme displayed a distinct substrate and product profile, highlighting different modes of action, with PaCel6A being the enzyme most similar to TrCel6A. PaCel6B was the only enzyme with higher specific activity on carboxymethylcellulose (CMC) than on Avicel and showed lower processivity than the others. Structural modeling predicts an open catalytic cleft, suggesting that PaCel6B is an endoglucanase. PMID:23645193

  8. RCF1-dependent respiratory supercomplexes are integral for lifespan-maintenance in a fungal ageing model

    PubMed Central

    Fischer, Fabian; Filippis, Christodoulos; Osiewacz, Heinz D.

    2015-01-01

    Mitochondrial respiratory supercomplexes (mtRSCs) are stoichiometric assemblies of electron transport chain (ETC) complexes in the inner mitochondrial membrane. They are hypothesized to regulate electron flow, the generation of reactive oxygen species (ROS) and to stabilize ETC complexes. Using the fungal ageing model Podospora anserina, we investigated the impact of homologues of the Saccharomyces cerevisiae respiratory supercomplex factors 1 and 2 (termed PaRCF1 and PaRCF2) on mtRSC formation, fitness and lifespan. Whereas PaRCF2’s role seems negligible, ablation of PaRCF1 alters size of monomeric complex IV, reduces the abundance of complex IV-containing supercomplexes, negatively affects vital functions and shortens lifespan. PaRcf1 overexpression slightly prolongs lifespan, though without appreciably influencing ETC organization. Overall, our results identify PaRCF1 as necessary yet not sufficient for mtRSC formation and demonstrate that PaRCF1-dependent stability of complex IV and associated supercomplexes is highly relevant for maintenance of the healthy lifespan in a eukaryotic model organism. PMID:26220011

  9. Mitochondrial intronic open reading frames in Podospora: Mobility and consecutive exonic sequence variations

    SciTech Connect

    Sellem, C.H.; Rossignol, M.; Belcour, L.

    1996-06-01

    The mitochondrial genome of 23 wild-type strains belonging to three different species of the filamentous fungus Podospora was examined. Among the 15 optical sequences identified are two intronic reading frames, nad1-i4-orf1 and cox1-i7-orf2. We show that the presence of these sequences was strictly correlated with tightly clustered nucleotide substitutions in the adjacent exon. This correlation applies to the presence or absence of closely related open reading frames (ORFs), found at the same genetic locations, in all the Pyrenomycete genera examined. The recent gain of these optional ORFs in the evolution of the genus Podospora probably account for such sequence differences. In the homoplasmic progeny from heteroplasmons constructed between Podospora strains differing by the presence of these optional ORFs, nad1-i4-orf1 and cox1-i7-orf2 appeared highly invasive. Sequence comparisons in the nad1-i4 intron of various strains of the Pyrenomycete family led us to propose a scenario of its evolution that includes several events of loss and gain of intronic ORFs. These results strongly reinforce the idea that group I intronic ORFs are mobile elements and that their transfer, and comcomitant modification of the adjacent exon, could participate in the modular evolution of mitochondrial genomes. 46 refs., 5 figs., 2 tabs.

  10. Cytosolic Ribosomal Mutations That Abolish Accumulation of Circular Intron in the Mitochondria without Preventing Senescence of Podospora Anserina

    PubMed Central

    Silar, P.; Koll, F.; Rossignol, M.

    1997-01-01

    The filamentous fungus Podospora anserina presents a degeneration syndrome called Senescence associated with mitochondrial DNA modifications. We show that mutations affecting the two different and interacting cytosolic ribosomal proteins (S7 and S19) systematically and specifically prevent the accumulation of senDNAα (a circular double-stranded DNA plasmid derived from the first intron of the mitochondrial cox1 gene or intron α) without abolishing Senescence nor affecting the accumulation of other usually observed mitochondrial DNA rearrangements. One of the mutant proteins is homologous to the Escherichia coli S4 and Saccharomyces cerevisiae S13 ribosomal proteins, known to be involved in accuracy control of cytosolic translation. The lack of accumulation of senDNAα seems to result from a nontrivial ribosomal alteration unrelated to accuracy control, indicating that S7 and S19 proteins have an additional function. The results strongly suggest that modified expression of nucleus-encoded proteins contributes to Senescence in P. anserina. These data do not fit well with some current models, which propose that intron α plays the role of the cytoplasmic and infectious Determinant of Senescence that was defined in early studies. PMID:9055079

  11. ALL AGES LEAD MODEL

    EPA Science Inventory

    The Integrated Exposure Uptake Biokinetic (IEUBK) Model for Lead in Children (version 0.99d) was released in March 1994, and has been widely accepted in the risk assessment community as a tool for implementing the site specific risk assessment process when the issue is childhood...

  12. Age models and their uncertainties

    NASA Astrophysics Data System (ADS)

    Marwan, N.; Rehfeld, K.; Goswami, B.; Breitenbach, S. F. M.; Kurths, J.

    2012-04-01

    The usefulness of a proxy record is largely dictated by accuracy and precision of its age model, i.e., its depth-age relationship. Only if age model uncertainties are minimized correlations or lead-lag relations can be reliably studied. Moreover, due to different dating strategies (14C, U-series, OSL dating, or counting of varves), dating errors or diverging age models lead to difficulties in comparing different palaeo proxy records. Uncertainties in the age model are even more important if an exact dating is necessary in order to calculate, e.g., data series of flux or rates (like dust flux records, pollen deposition rates). Several statistical approaches exist to handle the dating uncertainties themselves and to estimate the age-depth relationship. Nevertheless, linear interpolation is still the most commonly used method for age modeling. The uncertainties of a certain event at a given time due to the dating errors are often even completely neglected. Here we demonstrate the importance of considering dating errors and implications for the interpretation of variations in palaeo-climate proxy records from stalagmites (U-series dated). We present a simple approach for estimating age models and their confidence levels based on Monte Carlo methods and non-linear interpolation. This novel algorithm also allows for removing age reversals. Our approach delivers a time series of a proxy record with a value range for each age depth also, if desired, on an equidistant time axis. The algorithm is implemented in interactive scripts for use with MATLAB®, Octave, and FreeMat.

  13. Aging Research Using Mouse Models

    PubMed Central

    Ackert-Bicknell, Cheryl L.; Anderson, Laura; Sheehan, Susan; Hill, Warren G.; Chang, Bo; Churchill, Gary A.; Chesler, Elissa J.; Korstanje, Ron; Peters, Luanne L.

    2015-01-01

    Despite the dramatic increase in human lifespan over the past century, there remains pronounced variability in “health-span”, or the period of time in which one is generally healthy and free of disease. Much of the variability in health-span and lifespan is thought to be genetic in origin. Understanding the genetic mechanisms of aging and identifying ways to boost longevity is a primary goal in aging research. Here, we describe a pipeline of phenotypic assays for assessing mouse models of aging. This pipeline includes behavior/cognition testing, body composition analysis, and tests of kidney function, hematopoiesis, immune function and physical parameters. We also describe study design methods for assessing lifespan and health-span, and other important considerations when conducting aging research in the laboratory mouse. The tools and assays provided can assist researchers with understanding the correlative relationships between age-associated phenotypes and, ultimately, the role of specific genes in the aging process. PMID:26069080

  14. Overlapping Podospora anserina Transcriptional Responses to Bacterial and Fungal Non Self Indicate a Multilayered Innate Immune Response

    PubMed Central

    Lamacchia, Marina; Dyrka, Witold; Breton, Annick; Saupe, Sven J.; Paoletti, Mathieu

    2016-01-01

    Recognition and response to non self is essential to development and survival of all organisms. It can occur between individuals of the same species or between different organisms. Fungi are established models for conspecific non self recognition in the form of vegetative incompatibility (VI), a genetically controlled process initiating a programmed cell death (PCD) leading to the rejection of a fusion cell between genetically different isolates of the same species. In Podospora anserina VI is controlled by members of the hnwd gene family encoding for proteins analogous to NOD Like Receptors (NLR) immune receptors in eukaryotes. It was hypothesized that the hnwd controlled VI reaction was derived from the fungal innate immune response. Here we analyze the P. anserina transcriptional responses to two bacterial species, Serratia fonticola to which P. anserina survives and S. marcescens to which P. anserina succumbs, and compare these to the transcriptional response induced under VI conditions. Transcriptional responses to both bacteria largely overlap, however the number of genes regulated and magnitude of regulation is more important when P. anserina survives. Transcriptional responses to bacteria also overlap with the VI reaction for both up or down regulated gene sets. Genes up regulated tend to be clustered in the genome, and display limited phylogenetic distribution. In all three responses we observed genes related to autophagy to be up-regulated. Autophagy contributes to the fungal survival in all three conditions. Genes encoding for secondary metabolites and histidine kinase signaling are also up regulated in all three conditions. Transcriptional responses also display differences. Genes involved in response to oxidative stress, or encoding small secreted proteins are essentially expressed in response to bacteria, while genes encoding NLR proteins are expressed during VI. Most functions encoded in response to bacteria favor survival of the fungus while most

  15. Identification of a hypothetical protein from Podospora anserina as a nitroalkane oxidase.

    PubMed

    Tormos, José R; Taylor, Alexander B; Daubner, S Colette; Hart, P John; Fitzpatrick, Paul F

    2010-06-22

    The flavoprotein nitroalkane oxidase (NAO) from Fusarium oxysporum catalyzes the oxidation of primary and secondary nitroalkanes to their respective aldehydes and ketones. Structurally, the enzyme is a member of the acyl-CoA dehydrogenase superfamily. To date no enzymes other than that from F. oxysporum have been annotated as NAOs. To identify additional potential NAOs, the available database was searched for enzymes in which the active site residues Asp402, Arg409, and Ser276 were conserved. Of the several fungal enzymes identified in this fashion, PODANSg2158 from Podospora anserina was selected for expression and characterization. The recombinant enzyme is a flavoprotein with activity on nitroalkanes comparable to the F. oxysporum NAO, although the substrate specificity is somewhat different. Asp399, Arg406, and Ser273 in PODANSg2158 correspond to the active site triad in F. oxysporum NAO. The k(cat)/K(M)-pH profile with nitroethane shows a pK(a) of 5.9 that is assigned to Asp399 as the active site base. Mutation of Asp399 to asparagine decreases the k(cat)/K(M) value for nitroethane over 2 orders of magnitude. The R406K and S373A mutations decrease this kinetic parameter by 64- and 3-fold, respectively. The structure of PODANSg2158 has been determined at a resolution of 2.0 A, confirming its identification as an NAO. PMID:20481475

  16. Comparative analyses of Podospora anserina secretomes reveal a large array of lignocellulose-active enzymes.

    PubMed

    Poidevin, Laetitia; Berrin, Jean-Guy; Bennati-Granier, Chloé; Levasseur, Anthony; Herpoël-Gimbert, Isabelle; Chevret, Didier; Coutinho, Pedro M; Henrissat, Bernard; Heiss-Blanquet, Senta; Record, Eric

    2014-09-01

    The genome of the coprophilous fungus Podospora anserina harbors a large and highly diverse set of putative lignocellulose-acting enzymes. In this study, we investigated the enzymatic diversity of a broad range of P. anserina secretomes induced by various carbon sources (dextrin, glucose, xylose, arabinose, lactose, cellobiose, saccharose, Avicel, Solka-floc, birchwood xylan, wheat straw, maize bran, and sugar beet pulp (SBP)). Compared with the Trichoderma reesei enzymatic cocktail, P. anserina secretomes displayed similar cellulase, xylanase, and pectinase activities and greater arabinofuranosidase, arabinanase, and galactanase activities. The secretomes were further tested for their capacity to supplement a T. reesei cocktail. Four of them improved significantly the saccharification yield of steam-exploded wheat straw up to 48 %. Fine analysis of the P. anserina secretomes produced with Avicel and SBP using proteomics revealed a large array of CAZymes with a high number of GH6 and GH7 cellulases, CE1 esterases, GH43 arabinofuranosidases, and AA1 laccase-like multicopper oxidases. Moreover, a preponderance of AA9 (formerly GH61) was exclusively produced in the SBP condition. This study brings additional insights into the P. anserina enzymatic machinery and will facilitate the selection of promising targets for the development of future biorefineries. PMID:24695830

  17. Genetic and Molecular Analysis of a Long-Lived Strain of Podospora Anserina

    PubMed Central

    Silliker, M. E.; Cummings, D. J.

    1990-01-01

    A genetic and molecular analysis of a long-lived strain of Podospora anserina, Mn19, was undertaken to detect mutations in genes responsible for senescence. In crosses between Mn19 and wild type about 15% of the progeny were long-lived, regardless of the female parent. Molecular analysis of the long-lived progeny showed that none of the strains inherited a mtDNA rearrangement characteristic of the Mn19 parent. Instead, all long-lived strains initially inherited wild-type mtDNA. Over time the mtDNA of most long-lived strains underwent rearrangements, deletions and amplifications. The change over time in the presence of two previously characterized plasmids associated with either senescence or longevity was monitored. Crosses between Mn19 and its long-lived progeny also yielded only a small percent of individuals recovering from senescence. Analysis of mtDNA from crosses suggests that wild-type mtDNA from the paternal parent can be selected over mtDNA from the maternal parent. The life span phenotypes of progeny were not consistent with the hypothesis that mutations in a few nuclear genes were responsible for longevity. PMID:2397883

  18. [Experimental models of human skin aging].

    PubMed

    Nikolakis, G; Zoschke, C; Makrantonaki, E; Hausmann, C; Schäfer-Korting, M; Zouboulis, C C

    2016-02-01

    The skin is a representative model for the study of human aging. Despite the high regenerative capacity of the skin, skin physiology changes over the course of life. Medical and cosmetic research is trying to prevent aging, to slow, to stop, or to reverse it. Effects of age-related DNA damage and of changing skin structure on pharmacological parameters are largely unknown. This review article summarizes the state of scientific knowledge in the field of experimental models of human skin aging and shows approaches to improve organotypic skin models, to develop predictive models of aging, and improve aging research. PMID:26743051

  19. Natural Variation of Heterokaryon Incompatibility Gene het-c in Podospora anserina Reveals Diversifying Selection

    PubMed Central

    Bastiaans, Eric; Debets, Alfons J.M.; Aanen, Duur K.; van Diepeningen, Anne D.; Saupe, Sven J.; Paoletti, Mathieu

    2014-01-01

    In filamentous fungi, allorecognition takes the form of heterokaryon incompatibility, a cell death reaction triggered when genetically distinct hyphae fuse. Heterokaryon incompatibility is controlled by specific loci termed het-loci. In this article, we analyzed the natural variation in one such fungal allorecognition determinant, the het-c heterokaryon incompatibility locus of the filamentous ascomycete Podospora anserina. The het-c locus determines an allogenic incompatibility reaction together with two unlinked loci termed het-d and het-e. Each het-c allele is incompatible with a specific subset of the het-d and het-e alleles. We analyzed variability at the het-c locus in a population of 110 individuals, and in additional isolates from various localities. We identified a total of 11 het-c alleles, which define 7 distinct incompatibility specificity classes in combination with the known het-d and het-e alleles. We found that the het-c allorecognition gene of P. anserina is under diversifying selection. We find a highly unequal allele distribution of het-c in the population, which contrasts with the more balanced distribution of functional groups of het-c based on their allorecognition function. One explanation for the observed het-c diversity in the population is its function in allorecognition. However, alleles that are most efficient in allorecognition are rare. An alternative and not exclusive explanation for the observed diversity is that het-c is involved in pathogen recognition. In Arabidopsis thaliana, a homolog of het-c is a pathogen effector target, supporting this hypothesis. We hypothesize that the het-c diversity in P. anserina results from both its functions in pathogen-defense, and allorecognition. PMID:24448643

  20. Natural variation of heterokaryon incompatibility gene het-c in Podospora anserina reveals diversifying selection.

    PubMed

    Bastiaans, Eric; Debets, Alfons J M; Aanen, Duur K; van Diepeningen, Anne D; Saupe, Sven J; Paoletti, Mathieu

    2014-04-01

    In filamentous fungi, allorecognition takes the form of heterokaryon incompatibility, a cell death reaction triggered when genetically distinct hyphae fuse. Heterokaryon incompatibility is controlled by specific loci termed het-loci. In this article, we analyzed the natural variation in one such fungal allorecognition determinant, the het-c heterokaryon incompatibility locus of the filamentous ascomycete Podospora anserina. The het-c locus determines an allogenic incompatibility reaction together with two unlinked loci termed het-d and het-e. Each het-c allele is incompatible with a specific subset of the het-d and het-e alleles. We analyzed variability at the het-c locus in a population of 110 individuals, and in additional isolates from various localities. We identified a total of 11 het-c alleles, which define 7 distinct incompatibility specificity classes in combination with the known het-d and het-e alleles. We found that the het-c allorecognition gene of P. anserina is under diversifying selection. We find a highly unequal allele distribution of het-c in the population, which contrasts with the more balanced distribution of functional groups of het-c based on their allorecognition function. One explanation for the observed het-c diversity in the population is its function in allorecognition. However, alleles that are most efficient in allorecognition are rare. An alternative and not exclusive explanation for the observed diversity is that het-c is involved in pathogen recognition. In Arabidopsis thaliana, a homolog of het-c is a pathogen effector target, supporting this hypothesis. We hypothesize that the het-c diversity in P. anserina results from both its functions in pathogen-defense, and allorecognition. PMID:24448643

  1. Podospora anserina Hemicellulases Potentiate the Trichoderma reesei Secretome for Saccharification of Lignocellulosic Biomass▿

    PubMed Central

    Couturier, Marie; Haon, Mireille; Coutinho, Pedro M.; Henrissat, Bernard; Lesage-Meessen, Laurence; Berrin, Jean-Guy

    2011-01-01

    To improve the enzymatic hydrolysis (saccharification) of lignocellulosic biomass by Trichoderma reesei, a set of genes encoding putative polysaccharide-degrading enzymes were selected from the coprophilic fungus Podospora anserina using comparative genomics. Five hemicellulase-encoding genes were successfully cloned and expressed as secreted functional proteins in the yeast Pichia pastoris. These novel fungal CAZymes belonging to different glycoside hydrolase families (PaMan5A and PaMan26A mannanases, PaXyn11A xylanase, and PaAbf51A and PaAbf62A arabinofuranosidases) were able to break down their predicted cognate substrates. Although PaMan5A and PaMan26A displayed similar specificities toward a range of mannan substrates, they differed in their end products, suggesting differences in substrate binding. The N-terminal CBM35 module of PaMan26A displayed dual binding specificity toward xylan and mannan. PaXyn11A harboring a C-terminal CBM1 module efficiently degraded wheat arabinoxylan, releasing mainly xylobiose as end product. PaAbf51A and PaAbf62A arabinose-debranching enzymes exhibited differences in activity toward arabinose-containing substrates. Further investigation of the contribution made by each P. anserina auxiliary enzyme to the saccharification of wheat straw and spruce demonstrated that the endo-acting hemicellulases (PaXyn11A, PaMan5A, and PaMan26A) individually supplemented the secretome of the industrial T. reesei CL847 strain. The most striking effect was obtained with PaMan5A that improved the release of total sugars by 28% and of glucose by 18%, using spruce as lignocellulosic substrate. PMID:21037302

  2. The PaPsr1 and PaWhi2 genes are members of the regulatory network that connect stationary phase to mycelium differentiation and reproduction in Podospora anserina.

    PubMed

    Timpano, Hélène; Chan Ho Tong, Laetitia; Gautier, Valérie; Lalucque, Hervé; Silar, Philippe

    2016-09-01

    In filamentous fungi, entrance into stationary phase is complex as it is accompanied by several differentiation and developmental processes, including the synthesis of pigments, aerial hyphae, anastomoses and sporophores. The regulatory networks that control these processes are still incompletely known. The analysis of the "Impaired in the development of Crippled Growth (IDC)" mutants of the model filamentous ascomycete Podospora anserina has already yielded important information regarding the pathway regulating entrance into stationary phase. Here, the genes affected in two additional IDC mutants are identified as orthologues of the Saccharomyces cerevisiae WHI2 and PSR1 genes, known to regulate stationary phase in this yeast, arguing for a conserved role of these proteins throughout the evolution of ascomycetes. PMID:27353975

  3. COnstructing Proxy Records from Age models (COPRA)

    NASA Astrophysics Data System (ADS)

    Breitenbach, S. F. M.; Rehfeld, K.; Goswami, B.; Baldini, J. U. L.; Ridley, H. E.; Kennett, D. J.; Prufer, K. M.; Aquino, V. V.; Asmerom, Y.; Polyak, V. J.; Cheng, H.; Kurths, J.; Marwan, N.

    2012-10-01

    Reliable age models are fundamental for any palaeoclimate reconstruction. Available interpolation procedures between age control points are often inadequately reported, and very few translate age uncertainties to proxy uncertainties. Most available modeling algorithms do not allow incorporation of layer counted intervals to improve the confidence limits of the age model in question. We present a framework that allows detection and interactive handling of age reversals and hiatuses, depth-age modeling, and proxy-record reconstruction. Monte Carlo simulation and a translation procedure are used to assign a precise time scale to climate proxies and to translate dating uncertainties to uncertainties in the proxy values. The presented framework allows integration of incremental relative dating information to improve the final age model. The free software package COPRA1.0 facilitates easy interactive usage.

  4. Aging Successfully: A Four-Factor Model

    ERIC Educational Resources Information Center

    Lee, Pai-Lin; Lan, William; Yen, Tung-Wen

    2011-01-01

    The study was designed to validate a model for a successful aging process and examine the gender differences in the aging process. Three hundred twelve participants who were 65 or older completed a Taiwan Social Change Survey that measures four factors that define successful aging process: including physical, psychological, social support, and…

  5. Estimating Neuronal Ageing with Hidden Markov Models

    NASA Astrophysics Data System (ADS)

    Wang, Bing; Pham, Tuan D.

    2011-06-01

    Neuronal degeneration is widely observed in normal ageing, meanwhile the neurode-generative disease like Alzheimer's disease effects neuronal degeneration in a faster way which is considered as faster ageing. Early intervention of such disease could benefit subjects with potentials of positive clinical outcome, therefore, early detection of disease related brain structural alteration is required. In this paper, we propose a computational approach for modelling the MRI-based structure alteration with ageing using hidden Markov model. The proposed hidden Markov model based brain structural model encodes intracortical tissue/fluid distribution using discrete wavelet transformation and vector quantization. Further, it captures gray matter volume loss, which is capable of reflecting subtle intracortical changes with ageing. Experiments were carried out on healthy subjects to validate its accuracy and robustness. Results have shown its ability of predicting the brain age with prediction error of 1.98 years without training data, which shows better result than other age predition methods.

  6. Calibration of models using groundwater age

    USGS Publications Warehouse

    Sanford, W.

    2011-01-01

    There have been substantial efforts recently by geochemists to determine the age of groundwater (time since water entered the system) and its uncertainty, and by hydrologists to use these data to help calibrate groundwater models. This essay discusses the calibration of models using groundwater age, with conclusions that emphasize what is practical given current limitations rather than theoretical possibilities.

  7. Aging behavior and lifetime modeling for polycarbonate

    SciTech Connect

    Kahlen, S.; Wallner, G.M.; Lang, R.W.

    2010-05-15

    In this paper, polycarbonate (PC) as a material candidate for solar absorber applications is investigated as to the aging behavior at different temperatures in air and water. The aging conditioning was performed in air in the temperature range from 120 to 140 C and in water between 70 and 95 C. Tensile tests were performed on unaged and aged PC film specimens at ambient temperature using strain-to-break values as a performance indicator for the degree of aging. For PC the effect of aging was found to strongly depend on the aging conditions. Activation energy based lifetime prediction models according to various methods described in the literature were applied. The activation energies and corresponding lifetime predictions for the temperature range from 40 to 60 C in water and from 90 to 110 C in air derived from these models are compared and interpreted as to their practical relevance. (author)

  8. Heterologous production of cellobiose dehydrogenases from the basidiomycete Coprinopsis cinerea and the ascomycete Podospora anserina and their effect on saccharification of wheat straw.

    PubMed

    Turbe-Doan, Annick; Arfi, Yonathan; Record, Eric; Estrada-Alvarado, Isabel; Levasseur, Anthony

    2013-06-01

    Cellobiose dehydrogenases (CDHs) are extracellular glycosylated haemoflavoenzymes produced by many different wood-degrading and phytopathogenic fungi. Putative cellobiose dehydrogenase genes are recurrently discovered by genome sequencing projects in various phylogenetically distinct fungi. The genomes from the basidiomycete Coprinopsis cinerea and the ascomycete Podospora anserina were screened for candidate cdh genes, and one and three putative gene models were evidenced, respectively. Two putative cdh genes were selected and successfully expressed for the first time in Aspergillus niger. CDH activity was measured for both constructions (CDHcc and CDHpa), and both recombinant CDHs were purified to homogeneity and subsequently characterised. Kinetic constants were determined for several carbohydrates including β-1,4-linked di- and oligosaccharides. Optimal temperature and pH were 60 °C and 5 for CDHcc and 65-70 °C and 6 for CDHpa. Both CDHs showed a broad range of pH stability between 4 and 8. The effect of both CDHs on saccharification of micronized wheat straw by an industrial Trichoderma reesei secretome was determined. The addition of each CDH systematically decreased the release of total reducing sugars, but to different extents and according to the CDH concentration. Analytical methods were carried out to quantify the release of glucose, xylose and gluconic acid. An increase of glucose and xylose was measured at a low CDHcc concentration. At moderated and high CDHcc and CDHpa concentrations, glucose was severely reduced with a concomitant increase of gluconic acid. In conclusion, these results give new insights into the physical and chemical parameters and diversity of basidiomycetous and ascomycetous CDHs. These findings also demonstrated that CDH drastically influenced the saccharification on a natural substrate, and thus, CDH origin, concentration and potential enzymatic partners should be carefully considered in future artificial secretomes for

  9. A Model of Spirituality for Ageing Muslims.

    PubMed

    Ahmad, Mahjabeen; Khan, Shamsul

    2016-06-01

    Spirituality's influence on general well-being and its association with healthy ageing has been studied extensively. However, a different perspective has to be brought in when dealing with spirituality issues of ageing Muslims. Central to this perspective is the intertwining of religion and spirituality in Islam. This article will contribute to the understanding of the nature of Islamic spirituality and its immense importance in the life of a practicing ageing Muslim. Consequently, it will help care providers to include appropriate spiritual care in the care repertoire of a Muslim care recipient. It is assumed that the framework for a model of spirituality based on Islamic religious beliefs would help contextualise the relationship between spirituality and ageing Muslims. Not only challenges, but also the opportunities that old age provides for charting the spiritual journey have underpinned this model. PMID:25822881

  10. The Podospora rmp1 gene implicated in nucleus-mitochondria cross-talk encodes an essential protein whose subcellular location is developmentally regulated.

    PubMed Central

    Contamine, Véronique; Zickler, Denise; Picard, Marguerite

    2004-01-01

    It has been previously reported that, at the time of death, the Podospora anserina AS1-4 mutant strains accumulate specific deleted forms of the mitochondrial genome and that their life spans depend on two natural alleles (variants) of the rmp1 gene: AS1-4 rmp1-2 strains exhibit life spans strikingly longer than those of AS1-4 rmp1-1. Here, we show that rmp1 is an essential gene. In silico analyses of eight rmp1 natural alleles present in Podospora isolates and of the putative homologs of this orphan gene in other filamentous fungi suggest that rmp1 evolves rapidly. The RMP1 protein is localized in the mitochondrial and/or the cytosolic compartment, depending on cell type and developmental stage. Strains producing RMP1 without its mitochondrial targeting peptide are viable but exhibit vegetative and sexual defects. PMID:15020413

  11. Rodent models of aging bone: an update.

    PubMed

    Syed, Farhan A; Melim, Terry

    2011-12-01

    With an increase in the average life span especially in the Western hemisphere, there is renewed interest in treating maladies of old age including osteoporosis. Age-related bone loss and resultant osteoporosis substantially increase risk of fractures and morbidity in the geriatric population leading to both a decline in the quality of life for the elderly as well as a substantial burden on the health care system. Herein, we review recent research in murine and rodent models looking at how both extrinsic and intrinsic factors such as hormones, biochemicals, neuromodulators, inflammatory cytokines, oxidative stress, nutrition, and exercise influence the skeleton with age. Recent studies on the relationship between bone and fat in the marrow, and the fate of the marrow mesenchymal stromal cell population, which can give rise to either bone-forming osteoblasts or fat-forming adipocytic cells as a function of age, have also been highlighted. An appreciable range of studies using aging murine as well as cellular models are discussed, as these studies have broadened our understanding of the pathways and players in the aging bone. Impactful information regarding aging and the bone may then allow the application of better pharmacologic as well as nonpharmacologic regimens to alleviate bone loss due to aging. PMID:21918858

  12. Pathology of Mouse Models of Accelerated Aging.

    PubMed

    Harkema, L; Youssef, S A; de Bruin, A

    2016-03-01

    Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of "geroscience," which aims at elucidating the molecular mechanisms involved in aging. Progeroid mouse models are frequently used in geroscience as they provide insight into the molecular mechanisms that are involved in the highly complex process of natural aging. This review provides an overview of the most commonly reported nonneoplastic macroscopic and microscopic pathologic findings in progeroid mouse models (eg, osteoporosis, osteoarthritis, degenerative joint disease, intervertebral disc degeneration, kyphosis, sarcopenia, cutaneous atrophy, wound healing, hair loss, alopecia, lymphoid atrophy, cataract, corneal endothelial dystrophy, retinal degenerative diseases, and vascular remodeling). Furthermore, several shortcomings in pathologic analysis and descriptions of these models are discussed. Progeroid mouse models are valuable models for aging, but thorough knowledge of both the mouse strain background and the progeria-related phenotype is required to guide interpretation and translation of the pathology data. PMID:26864891

  13. Species ages in neutral biodiversity models.

    PubMed

    Chisholm, Ryan A; O'Dwyer, James P

    2014-05-01

    Biogeography seeks to understand the mechanisms that drive biodiversity across long temporal and large spatial scales. Theoretical models of biogeography can be tested by comparing their predictions of quantities such as species ages against empirical estimates. It has previously been claimed that the neutral theory of biodiversity and biogeography predicts species ages that are unrealistically long. Any improved theory of biodiversity must rectify this problem, but first it is necessary to quantify the problem precisely. Here we provide analytical expressions for species ages in neutral biodiversity communities. We analyse a spatially implicit metacommunity model and solve for both the zero-sum and non-zero-sum cases. We explain why our new expressions are, in the context of biodiversity, usually more appropriate than those previously imported from neutral molecular evolution. Because of the time symmetry of the spatially implicit neutral model, our expressions also lead directly to formulas for species persistence times and species lifetimes. We use our new expressions to estimate species ages of forest trees under a neutral model and find that they are about an order of magnitude shorter than those predicted previously but still unrealistically long. In light of our results, we discuss different models of biogeography that may solve the problem of species ages. PMID:24530891

  14. Mathematical Modelling of Metabolic Regulation in Aging

    PubMed Central

    Mc Auley, Mark T.; Mooney, Kathleen M.; Angell, Peter J.; Wilkinson, Stephen J.

    2015-01-01

    The underlying cellular mechanisms that characterize aging are complex and multifaceted. However, it is emerging that aging could be regulated by two distinct metabolic hubs. These hubs are the pathway defined by the mammalian target of rapamycin (mTOR) and that defined by the NAD+-dependent deacetylase enzyme, SIRT1. Recent experimental evidence suggests that there is crosstalk between these two important pathways; however, the mechanisms underpinning their interaction(s) remains poorly understood. In this review, we propose using computational modelling in tandem with experimentation to delineate the mechanism(s). We briefly discuss the main modelling frameworks that could be used to disentangle this relationship and present a reduced reaction pathway that could be modelled. We conclude by outlining the limitations of computational modelling and by discussing opportunities for future progress in this area. PMID:25923415

  15. Mathematical modelling of metabolic regulation in aging.

    PubMed

    Auley, Mark T Mc; Mooney, Kathleen M; Angell, Peter J; Wilkinson, Stephen J

    2015-01-01

    The underlying cellular mechanisms that characterize aging are complex and multifaceted. However, it is emerging that aging could be regulated by two distinct metabolic hubs. These hubs are the pathway defined by the mammalian target of rapamycin (mTOR) and that defined by the NAD+-dependent deacetylase enzyme, SIRT1. Recent experimental evidence suggests that there is crosstalk between these two important pathways; however, the mechanisms underpinning their interaction(s) remains poorly understood. In this review, we propose using computational modelling in tandem with experimentation to delineate the mechanism(s). We briefly discuss the main modelling frameworks that could be used to disentangle this relationship and present a reduced reaction pathway that could be modelled. We conclude by outlining the limitations of computational modelling and by discussing opportunities for future progress in this area. PMID:25923415

  16. Love Kills:. Simulations in Penna Ageing Model

    NASA Astrophysics Data System (ADS)

    Stauffer, Dietrich; Cebrat, Stanisław; Penna, T. J. P.; Sousa, A. O.

    The standard Penna ageing model with sexual reproduction is enlarged by adding additional bit-strings for love: Marriage happens only if the male love strings are sufficiently different from the female ones. We simulate at what level of required difference the population dies out.

  17. Modeling and measuring extravascular hemoglobin: aging contusions

    NASA Astrophysics Data System (ADS)

    Lines, Collin; Kim, Oleg; Duffy, Susan; Alber, Mark; Crawford, Gregory P.

    2011-07-01

    Medical expertise is frequently elicited to aid in determining the age and the cause of the trauma or injury. Child protection and law enforcement frequently rely on the physical assessment of the trauma which involves delineating intentional from unintentional types of trauma. Recent studies have shown that current methods to assess the age of traumatic injuries are highly inaccurate and do not give reasonable predictions. Hemoglobin is one of the strongest chromophores in human tissues. Transport of hemoglobin and its breakdown products in tissue determines the spectrophotometric characteristics of the skin and its variations in time. Therefore, measurements of diffuse reflective spectra of the skin allow noninvasive screening. This paper reviews potential transmission and diffusive reflection spectroscopy based techniques and predictive and quantitative modeling methods assisting in efficient retrieval of the age of extravascular contusions. This paper then presents a novel Monte Carlo technique for 3D photon tracking and blood transport model. In future studies, clinically obtained spectra will be used to validate the model as well as fine-tune coefficients for absorption. It is the goal of this study to develop a model that would allow a non-invasive, accurate determination of the age of a bruise.

  18. Normal brain ageing: models and mechanisms

    PubMed Central

    Toescu, Emil C

    2005-01-01

    Normal ageing is associated with a degree of decline in a number of cognitive functions. Apart from the issues raised by the current attempts to expand the lifespan, understanding the mechanisms and the detailed metabolic interactions involved in the process of normal neuronal ageing continues to be a challenge. One model, supported by a significant amount of experimental evidence, views the cellular ageing as a metabolic state characterized by an altered function of the metabolic triad: mitochondria–reactive oxygen species (ROS)–intracellular Ca2+. The perturbation in the relationship between the members of this metabolic triad generate a state of decreased homeostatic reserve, in which the aged neurons could maintain adequate function during normal activity, as demonstrated by the fact that normal ageing is not associated with widespread neuronal loss, but become increasingly vulnerable to the effects of excessive metabolic loads, usually associated with trauma, ischaemia or neurodegenerative processes. This review will concentrate on some of the evidence showing altered mitochondrial function with ageing and also discuss some of the functional consequences that would result from such events, such as alterations in mitochondrial Ca2+ homeostasis, ATP production and generation of ROS. PMID:16321805

  19. Hydra, a powerful model for aging studies

    PubMed Central

    Tomczyk, Szymon; Fischer, Kathleen; Austad, Steven; Galliot, Brigitte

    2015-01-01

    Cnidarian Hydra polyps escape senescence, most likely due to the robust activity of their three stem cell populations. These stem cells continuously self-renew in the body column and differentiate at the extremities following a tightly coordinated spatial pattern. Paul Brien showed in 1953 that in one particular species, Hydra oligactis, cold-dependent sexual differentiation leads to rapid aging and death. Here, we review the features of this inducible aging phenotype. These cellular alterations, detected several weeks after aging was induced, are characterized by a decreasing density of somatic interstitial cell derivatives, a disorganization of the apical nervous system, and a disorganization of myofibers of the epithelial cells. Consequently, tissue replacement required to maintain homeostasis, feeding behavior, and contractility of the animal are dramatically affected. Interestingly, this aging phenotype is not observed in all H. oligactis strains, thus providing a powerful experimental model for investigations of the genetic control of aging. Given the presence in the cnidarian genome of a large number of human orthologs that have been lost in ecdysozoans, such approaches might help uncover novel regulators of aging in vertebrates. PMID:26120246

  20. Altered Mating-Type Identity in the Fungus Podospora Anserina Leads to Selfish Nuclei, Uniparental Progeny, and Haploid Meiosis

    PubMed Central

    Zickler, D.; Arnaise, S.; Coppin, E.; Debuchy, R.; Picard, M.

    1995-01-01

    In wild-type crosses of the filamentous ascomycete Podospora anserina, after fertilization, only nuclei of opposite mating type can form dikaryons that undergo karyogamy and meiosis, producing biparental progeny. To determine the role played by the mating type in these steps, the four mat genes were mutagenized in vitro and introduced into a strain deleted for its mat locus. Genetic and cytological analyses of these mutant strains, crossed to each other and to wild type, showed that mating-type information is required for recognition of nuclear identity during the early steps of sexual reproduction. In crosses with strains carrying a mating-type mutation, two unusual developmental patterns were observed: monokaryotic cells, resulting in haploid meiosis, and uniparental dikaryotic cells providing, after karyogamy and meiosis, a uniparental progeny. Altered mating-type identity leads to selfish behavior of the mutant nucleus: it migrates alone or paired, ignoring its wild-type partner in all mutant X wild-type crosses. This behavior is nucleus-autonomous because, in the same cytoplasm, the wild-type nuclei form only biparental dikaryons. In P. anserina, mat genes are thus required to ensure a biparental dikaryotic state but appear dispensable for later stages, such as meiosis and sporulation. PMID:7498731

  1. Cello-oligosaccharide oxidation reveals differences between two lytic polysaccharide monooxygenases (family GH61) from Podospora anserina.

    PubMed

    Bey, Mathieu; Zhou, Simeng; Poidevin, Laetitia; Henrissat, Bernard; Coutinho, Pedro M; Berrin, Jean-Guy; Sigoillot, Jean-Claude

    2013-01-01

    The genome of the coprophilic ascomycete Podospora anserina encodes 33 different genes encoding copper-dependent lytic polysaccharide monooxygenases (LPMOs) from glycoside hydrolase family 61 (GH61). In this study, two of these enzymes (P. anserina GH61A [PaGH61A] and PaGH61B), which both harbored a family 1 carbohydrate binding module, were successfully produced in Pichia pastoris. Synergistic cooperation between PaGH61A or PaGH61B with the cellobiose dehydrogenase (CDH) of Pycnoporus cinnabarinus on cellulose resulted in the formation of oxidized and nonoxidized cello-oligosaccharides. A striking difference between PaGH61A and PaGH61B was observed through the identification of the products, among which were doubly and triply oxidized cellodextrins, which were released only by the combination of PaGH61B with CDH. The mass spectrometry fragmentation patterns of these oxidized products could be consistent with oxidation at the C-6 position with a geminal diol group. The different properties of PaGH61A and PaGH61B and their effect on the interaction with CDH are discussed in regard to the proposed in vivo function of the CDH/GH61 enzyme system in oxidative cellulose hydrolysis. PMID:23124232

  2. Altering a gene involved in nuclear distribution increases the repeat-induced point mutation process in the fungus Podospora anserina.

    PubMed Central

    Bouhouche, Khaled; Zickler, Denise; Debuchy, Robert; Arnaise, Sylvie

    2004-01-01

    Repeat-induced point mutation (RIP) is a homology-dependent gene-silencing mechanism that introduces C:G-to-T:A transitions in duplicated DNA segments. Cis-duplicated sequences can also be affected by another mechanism called premeiotic recombination (PR). Both are active over the sexual cycle of some filamentous fungi, e.g., Neurospora crassa and Podospora anserina. During the sexual cycle, several developmental steps require precise nuclear movement and positioning, but connections between RIP, PR, and nuclear distributions have not yet been established. Previous work has led to the isolation of ami1, the P. anserina ortholog of the Aspergillus nidulans apsA gene, which is required for nuclear positioning. We show here that ami1 is involved in nuclear distribution during the sexual cycle and that alteration of ami1 delays the fruiting-body development. We also demonstrate that ami1 alteration affects loss of transgene functions during the sexual cycle. Genetically linked multiple copies of transgenes are affected by RIP and PR much more frequently in an ami1 mutant cross than in a wild-type cross. Our results suggest that the developmental slowdown of the ami1 mutant during the period of RIP and PR increases time exposure to the duplication detection system and thus increases the frequency of RIP and PR. PMID:15166143

  3. Co-expression of the mating-type genes involved in internuclear recognition is lethal in Podospora anserina.

    PubMed Central

    Coppin, E; Debuchy, R

    2000-01-01

    In the heterothallic filamentous fungus Podospora anserina, four mating-type genes encoding transcriptional factors have been characterized: FPR1 in the mat+ sequence and FMR1, SMR1, and SMR2 in the alternative mat- sequence. Fertilization is controlled by FPR1 and FMR1. After fertilization, male and female nuclei, which have divided in the same cell, form mat+/mat- pairs during migration into the ascogenous hyphae. Previous data indicate that the formation of mat+/mat- pairs is controlled by FPR1, FMR1, and SMR2. SMR1 was postulated to be necessary for initial development of ascogenous hyphae. In this study, we investigated the transcriptional control of the mat genes by seeking mat transcripts during the vegetative and sexual phase and fusing their promoter to a reporter gene. The data indicate that FMR1 and FPR1 are expressed in both mycelia and perithecia, whereas SMR1 and SMR2 are transcribed in perithecia. Increased or induced vegetative expression of the four mat genes has no effect when the recombined gene is solely in the wild-type strain. However, the combination of resident FPR1 with deregulated SMR2 and overexpressed FMR1 in the same nucleus is lethal. This lethality is suppressed by the expression of SMR1, confirming that SMR1 operates downstream of the other mat genes. PMID:10835389

  4. Production of sordarin and related metabolites by the coprophilous fungus Podospora pleiospora in submerged culture and in its natural substrate.

    PubMed

    Weber, Roland W S; Meffert, Anja; Anke, Heidrun; Sterner, Olov

    2005-05-01

    Rabbit pellets collected from the field were colonized by Podospora pleiospora at the exclusion of other coprophilous fungi, suggesting antibiosis. In liquid culture, P. pleiospora produced sordarin (1); sordarin B (2), a new compound in which sordarose is replaced by rhamnose; hydroxysordarin (3); and sordaricin (4). The major compounds 1 and 2 exhibited minimum inhibitory concentrations of 0.5-2.5 microg ml(-1) against the yeasts Nematospora coryli and Sporobolomyces roseus, but showed little or no activity against bacteria or coprophilous filamentous fungi. In liquid culture, the production of 1 and 2 together amounted to 2.7 microg ml(-1), whereas in rabbit dung only 1 was produced at a similar concentration (2.3 microg g(-1) fresh weight). The biosynthesis of these substances was unaffected by the presence of inoculum of other fungi tested (Sporobolomyces roseus or Penicillium claviforme) in liquid culture or on dung. Sordarin-type natural products are therefore synthesized by P. pleiospora at sufficiently high concentrations to account for antibiosis against yeasts, but not against filamentous fungi. PMID:16018317

  5. Cello-Oligosaccharide Oxidation Reveals Differences between Two Lytic Polysaccharide Monooxygenases (Family GH61) from Podospora anserina

    PubMed Central

    Bey, Mathieu; Zhou, Simeng; Poidevin, Laetitia; Henrissat, Bernard; Coutinho, Pedro M.; Sigoillot, Jean-Claude

    2013-01-01

    The genome of the coprophilic ascomycete Podospora anserina encodes 33 different genes encoding copper-dependent lytic polysaccharide monooxygenases (LPMOs) from glycoside hydrolase family 61 (GH61). In this study, two of these enzymes (P. anserina GH61A [PaGH61A] and PaGH61B), which both harbored a family 1 carbohydrate binding module, were successfully produced in Pichia pastoris. Synergistic cooperation between PaGH61A or PaGH61B with the cellobiose dehydrogenase (CDH) of Pycnoporus cinnabarinus on cellulose resulted in the formation of oxidized and nonoxidized cello-oligosaccharides. A striking difference between PaGH61A and PaGH61B was observed through the identification of the products, among which were doubly and triply oxidized cellodextrins, which were released only by the combination of PaGH61B with CDH. The mass spectrometry fragmentation patterns of these oxidized products could be consistent with oxidation at the C-6 position with a geminal diol group. The different properties of PaGH61A and PaGH61B and their effect on the interaction with CDH are discussed in regard to the proposed in vivo function of the CDH/GH61 enzyme system in oxidative cellulose hydrolysis. PMID:23124232

  6. Regulation of gene expression during the vegetative incompatibility reaction in Podospora anserina. Characterization of three induced genes.

    PubMed Central

    Bourges, N; Groppi, A; Barreau, C; Clavé, C; Bégueret, J

    1998-01-01

    Vegetative incompatibility in fungi limits the formation of viable heterokaryons. It results from the coexpression of incompatible genes in the heterokaryotic cells and leads to a cell death reaction. In Podospora anserina, a modification of gene expression takes place during this reaction, including a strong decrease of total RNA synthesis and the appearance of a new set of proteins. Using in vitro translation of mRNA and separation of protein products by two-dimensional gel electrophoresis, we have shown that the mRNA content of cells is qualitatively modified during the progress of the incompatibility reaction. Thus, gene expression during vegetative incompatibility is regulated, at least in part, by variation of the mRNA content of specific genes. A subtractive cDNA library enriched in sequences preferentially expressed during incompatibility was constructed. This library was used to identify genomic loci corresponding to genes whose mRNA is induced during incompatibility. Three such genes were characterized and named idi genes for genes induced during incompatibility. Their expression profiles suggest that they may be involved in different steps of the incompatibility reaction. The putative IDI proteins encoded by these genes are small proteins with signal peptides. IDI-2 protein is a cysteine-rich protein. IDI-2 and IDI-3 proteins display some similarity in a tryptophan-rich region. PMID:9755195

  7. Animal models of age related macular degeneration

    PubMed Central

    Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

  8. A life span model of successful aging.

    PubMed

    Schulz, R; Heckhausen, J

    1996-07-01

    To lay the foundation for our model, we first describe existing conceptions of successful aging, underlying assumptions of development, and criteria for success. The model presented extends the discourse on this topic in three directions: (a) It frames the discussion of successful aging in the broader context of life course development; (b) it accounts for both normative and nonnormative (i.e., exceptional) success; and (c) it integrates motivational processes into a theory of successful aging. Successful aging is equated with the development and maintenance of primary control throughout the life course, which is achieved through control-related processes that optimize selection and failure compensation functions. Selection processes regulate the choice of action goals so that diversity is maintained and positive and negative trade-offs between performance domains and life stages are taken into account. Compensation mechanisms serve to maintain, enhance, and remediate competencies and motivational resources after failure experiences. Both compensation and selection processes are motivated by desires for primary control and can be characterized in terms of primary and secondary control processes. PMID:8694390

  9. Genetic and functional investigation of Zn(2)Cys(6) transcription factors RSE2 and RSE3 in Podospora anserina.

    PubMed

    Bovier, Elodie; Sellem, Carole H; Humbert, Adeline; Sainsard-Chanet, Annie

    2014-01-01

    In Podospora anserina, the two zinc cluster proteins RSE2 and RSE3 are essential for the expression of the gene encoding the alternative oxidase (aox) when the mitochondrial electron transport chain is impaired. In parallel, they activated the expression of gluconeogenic genes encoding phosphoenolpyruvate carboxykinase (pck) and fructose-1,6-biphosphatase (fbp). Orthologues of these transcription factors are present in a wide range of filamentous fungi, and no other role than the regulation of these three genes has been evidenced so far. In order to better understand the function and the organization of RSE2 and RSE3, we conducted a saturated genetic screen based on the constitutive expression of the aox gene. We identified 10 independent mutations in 9 positions in rse2 and 11 mutations in 5 positions in rse3. Deletions were generated at some of these positions and the effects analyzed. This analysis suggests the presence of central regulatory domains and a C-terminal activation domain in both proteins. Microarray analysis revealed 598 genes that were differentially expressed in the strains containing gain- or loss-of-function mutations in rse2 or rse3. It showed that in addition to aox, fbp, and pck, RSE2 and RSE3 regulate the expression of genes encoding the alternative NADH dehydrogenase, a Zn2Cys6 transcription factor, a flavohemoglobin, and various hydrolases. As a complement to expression data, a metabolome profiling approach revealed that both an rse2 gain-of-function mutation and growth on antimycin result in similar metabolic alterations in amino acids, fatty acids, and α-ketoglutarate pools. PMID:24186951

  10. Maintaining Two Mating Types: Structure of the Mating Type Locus and Its Role in Heterokaryosis in Podospora anserina

    PubMed Central

    Grognet, Pierre; Bidard, Frédérique; Kuchly, Claire; Tong, Laetitia Chan Ho; Coppin, Evelyne; Benkhali, Jinane Ait; Couloux, Arnaud; Wincker, Patrick; Debuchy, Robert; Silar, Philippe

    2014-01-01

    Pseudo-homothallism is a reproductive strategy elected by some fungi producing heterokaryotic sexual spores containing genetically different but sexually compatible nuclei. This lifestyle appears as a compromise between true homothallism (self-fertility with predominant inbreeding) and complete heterothallism (with exclusive outcrossing). However, pseudohomothallic species face the problem of maintaining heterokaryotic mycelia to fully benefit from this lifestyle, as homokaryons are self-sterile. Here, we report on the structure of chromosome 1 in mat+ and mat− isolates of strain S of the pseudohomothallic fungus Podospora anserina. Chromosome 1 contains either one of the mat+ and mat− mating types of P. anserina, which is mostly found in nature as a mat+/mat− heterokaryotic mycelium harboring sexually compatible nuclei. We identified a “mat” region ∼0.8 Mb long, devoid of meiotic recombination and containing the mating-type idiomorphs, which is a candidate to be involved in the maintenance of the heterokaryotic state, since the S mat+ and S mat− strains have different physiology that may enable hybrid-vigor-like phenomena in the heterokaryons. The mat region contains 229 coding sequences. A total of 687 polymorphisms were detected between the S mat+ and S mat− chromosomes. Importantly, the mat region is colinear between both chromosomes, which calls for an original mechanism of recombination inhibition. Microarray analyses revealed that 10% of the P. anserina genes have different transcriptional profiles in S mat+ and S mat−, in line with their different phenotypes. Finally, we show that the heterokaryotic state is faithfully maintained during mycelium growth of P. anserina, yet mat+/mat+ and mat−/mat− heterokaryons are as stable as mat+/mat− ones, evidencing a maintenance of heterokaryosis that does not rely on fitness-enhancing complementation between the S mat+ and S mat− strains. PMID:24558260

  11. Biological Roles of the Podospora anserina Mitochondrial Lon Protease and the Importance of Its N-Domain

    PubMed Central

    Adam, Céline; Picard, Marguerite; Déquard-Chablat, Michelle; Sellem, Carole H.; Denmat, Sylvie Hermann-Le; Contamine, Véronique

    2012-01-01

    Mitochondria have their own ATP-dependent proteases that maintain the functional state of the organelle. All multicellular eukaryotes, including filamentous fungi, possess the same set of mitochondrial proteases, unlike in unicellular yeasts, where ClpXP, one of the two matricial proteases, is absent. Despite the presence of ClpXP in the filamentous fungus Podospora anserina, deletion of the gene encoding the other matricial protease, PaLon1, leads to lethality at high and low temperatures, indicating that PaLON1 plays a main role in protein quality control. Under normal physiological conditions, the PaLon1 deletion is viable but decreases life span. PaLon1 deletion also leads to defects in two steps during development, ascospore germination and sexual reproduction, which suggests that PaLON1 ensures important regulatory functions during fungal development. Mitochondrial Lon proteases are composed of a central ATPase domain flanked by a large non-catalytic N-domain and a C-terminal protease domain. We found that three mutations in the N-domain of PaLON1 affected fungal life cycle, PaLON1 protein expression and mitochondrial proteolytic activity, which reveals the functional importance of the N-domain of the mitochondrial Lon protease. All PaLon1 mutations affected the C-terminal part of the N-domain. Considering that the C-terminal part is predicted to have an α helical arrangement in which the number, length and position of the helices are conserved with the solved structure of its bacterial homologs, we propose that this all-helical structure participates in Lon substrate interaction. PMID:22693589

  12. COnstructing Proxy-Record Age models (COPRA)

    NASA Astrophysics Data System (ADS)

    Marwan, Norbert; Rehfeld, Kira; Goswami, Bedartha; Breitenbach, Sebastian F. M.; Kurths, Jürgen

    2013-04-01

    Reliable age models are fundamental for any palaeoclimate reconstruction. The increasing availability of high-resolution palaeoclimate time series, e.g., based on speleothem archives, has attracted some new activity in the development of alternative and novel approaches for reconstructing chronologies. Challenges in this effort are (semi-)automatic outlier, reversal, and hiatus detection and treatment, as well as the inclusion of information on age uncertainties and independent layer counting to improve the overall precision of the chronology. However, different dating strategies, different kinds of palaeoarchive formation, dating uncertainties, and different chronology construction methods cause a limited comparability of the different palaeoclimate records. We present a recently developed framework which addresses these challenges and which allows the incorporation of layer counting data to improve the reconstructed chronology of a given time series. Moreover, we introduce the concept of an "absolute" time scale, a common time axis which works as an invariant reference allowing the comparison of different palaeoclimate records. This concept translates the age uncertainties into uncertainties in the proxy values. This framework is implemented as an open source software (COPRA) for Octave and Matlab.

  13. Towards an Analytical Age-Dependent Model of Contrast Sensitivity Functions for an Ageing Society

    PubMed Central

    Joulan, Karine; Brémond, Roland

    2015-01-01

    The Contrast Sensitivity Function (CSF) describes how the visibility of a grating depends on the stimulus spatial frequency. Many published CSF data have demonstrated that contrast sensitivity declines with age. However, an age-dependent analytical model of the CSF is not available to date. In this paper, we propose such an analytical CSF model based on visual mechanisms, taking into account the age factor. To this end, we have extended an existing model from Barten (1999), taking into account the dependencies of this model's optical and physiological parameters on age. Age-dependent models of the cones and ganglion cells densities, the optical and neural MTF, and optical and neural noise are proposed, based on published data. The proposed age-dependent CSF is finally tested against available experimental data, with fair results. Such an age-dependent model may be beneficial when designing real-time age-dependent image coding and display applications. PMID:26078994

  14. Creating Better School-Age Care Jobs: Model Work Standards.

    ERIC Educational Resources Information Center

    Haack, Peggy

    Built on the premise that good school-age care jobs are the cornerstone of high-quality services for school-age youth and their families, this guide presents model work standards for school-age care providers. The guide begins with a description of the strengths and challenges of the school-age care profession. The model work standards are…

  15. DNA-dependent RNA polymerase III from the fungus Podospora comata. Purification, subunit structure and comparison with the homologous enzyme of a related species.

    PubMed

    Barreau, C; Begueret, J

    1982-12-15

    DNA-dependent RNA polymerase III has been purified to homogeneity from the filamentous fungus Podospora comata. The enzyme was extracted at low ionic strength, separated from the polymerases I and II by DEAE-Sephadex chromatography and purified by heparin-Sepharose and phosphocellulose chromatography; 0.1-0.2 mg highly purified homogeneous enzyme with a specific activity of 220 units/mg could be obtained from 2 kg wet mycelium. The subunit composition of the enzyme was determined after sodium dodecyl sulphate/polyacrylamide gel electrophoresis; thirteen putative subunits of molecular weight 174000 (a), 129000 b), 87000 (c), 50000 (d), 39000 (e), 23500 (f), 21000 (g), 19000 (h), 17000 (i), 16500 (j), 13500 (k), 11000 (l) and 10000 (m) were identified. All of the polypeptide components of the enzyme are present in about integral stoichiometric amounts as judged by dye binding. The presence of subunit Mr = 87000 in a molar ratio 1:1 is necessary to obtain very active enzyme. Thirteen homologous subunits were observed in a preparation of RNA polymerase III from Podospora anserina, which is a related species. Only subunit i is different in the two species. PMID:7151805

  16. Virginia Opossums, Minimum Reproduction Age and Predators in the Penna Aging Model

    NASA Astrophysics Data System (ADS)

    Altevolmer, A. K.

    Age-specific predators are introduced into the Penna model of biological aging. It is shown that populations with a variable minimum reproduction age find a stable state with an earlier onset of reproduction, if older ages are eaten by the predators. This behavior agrees with the demographic data of the Virgina opossum.

  17. Evolutionary model with genetics, aging, and knowledge

    NASA Astrophysics Data System (ADS)

    Bustillos, Armando Ticona; de Oliveira, Paulo Murilo

    2004-02-01

    We represent a process of learning by using bit strings, where 1 bits represent the knowledge acquired by individuals. Two ways of learning are considered: individual learning by trial and error, and social learning by copying knowledge from other individuals or from parents in the case of species with parental care. The age-structured bit string allows us to study how knowledge is accumulated during life and its influence over the genetic pool of a population after many generations. We use the Penna model to represent the genetic inheritance of each individual. In order to study how the accumulated knowledge influences the survival process, we include it to help individuals to avoid the various death situations. Modifications in the Verhulst factor do not show any special feature due to its random nature. However, by adding years to life as a function of the accumulated knowledge, we observe an improvement of the survival rates while the genetic fitness of the population becomes worse. In this latter case, knowledge becomes more important in the last years of life where individuals are threatened by diseases. Effects of offspring overprotection and differences between individual and social learning can also be observed. Sexual selection as a function of knowledge shows some effects when fidelity is imposed.

  18. Mitochondrial DNA-deficient models and aging.

    PubMed

    Olgun, Abdullah; Akman, Serif

    2007-04-01

    Human mitochondrial DNA (mtDNA) encodes 13 subunits of oxidative phosphorylation (OXPHOS) enzyme complexes I, III, IV, and V except complex II. MtDNA is more sensitive to oxidative damage than nuclear DNA. MtDNA defects are involved in many pathologies including aging. Several mtDNA-deficient cell culture, yeast, and animal models were generated to study the role of mtDNA in many physiological processes. Ethidium bromide (EB), an agent that is known to inhibit mtDNA replication with a negligible effect on nuclear DNA, is generally used to generate mtDNA-deficient models. The antibiotics chloramphenicol and doxycycline, which were known to inhibit mitochondrial translation, were also used to generate the same phenotype. Cultured mtDNA-deficient cells need uridine and pyruvate to survive. At the organismal level, uridine can be supplemented, but pyruvate supplementation can cause a worser phenotype because of lactic acidosis. In C. elegans, EB, when used during larval development, increases life span, but decreases, when used after the beginning of adult stage. This should be kept in mind since mitochondria-related genes are generally detected in genome-wide screening studies for longevity. We believe that conditional knockout studies need to be carried out for these genes after reaching adulthood. MtDNA mutator mouse did not show an increase of free radical production. Therefore, the downstream phenomena to mtDNA defects are likely ineffective pyrimidine synthesis (dihydroorotate dehydrogenase, DHODH, needs a functional respiratory chain) and excess NADH (decreased NAD pool) in addition to free radicals. PMID:17460185

  19. Models to explore genetics of human aging.

    PubMed

    Karasik, David; Newman, Anne

    2015-01-01

    Genetic studies have bestowed insight into the biological mechanisms underlying inter-individual differences in susceptibility to (or resistance to) organisms’ aging. Recent advances in molecular and genetic epidemiology provide tools to explore the genetic sources of the variability in biological aging in humans. To be successful, the genetic study of a complex condition such as aging requires the clear definition of essential traits that can characterize the aging process phenotypically. Phenotypes of human aging have long relied on mortality rate or exceptional longevity. Genome-wide association studies (GWAS) have been shown to present an unbiased approach to the identification of new candidate genes for human diseases. The GWAS approach can also be used for positive health phenotypes such as longevity or a delay in age-related chronic disease, as well as for other age related changes such as loss of telomere length or lens transparency. Sequencing, either in targeted regions or across the whole genome can further identify rare variation that may contribute to the biological aging mechanisms. To date, the results of the GWAS for longevity are rather disappointing, possibly in part due to the small number of individuals with GWAS data who have reached advanced old age.Human aging phenotypes are needed that can be assessed prior to death, and should be both heritable and validated as predictors of longevity. Potentially, phenotypes that focus on “successful” or “healthy” aging will be more powerful as they can be measured in large numbers of people and also are clinically relevant.We postulate that construction of an integrated phenotype of aging can be achieved capitalizing on multiple traits that may have weak correlations, but a shared underlying genetic architecture. This is based on a hypothesis that convergent results from multiple individual aging-related traits will point out the pleiotropic signals responsible for the overall rate of aging of

  20. Successful Aging as a Continuum of Functional Independence: Lessons from Physical Disability Models of Aging

    PubMed Central

    Lowry, Kristin A.; Vallejo, Abbe N.; Studenski, Stephanie A.

    2011-01-01

    Successful aging is a multidimensional construct that could be viewed as a continuum of achievement. Based on the disability model proposed by the WHO International Classification of Functioning, Disability and Health, successful aging includes not only the presence or absence of disease, but also aspects of mobility and social participation. Here we review definitions of successful aging and discuss relevance of the disability model in the evaluation of successful aging and frailty. In particular, we summarize evidences that highlight the importance of measures of mobility (ability to walk and perform activities of daily living), and social participation in identifying and locating older adults across the range of the successful aging continuum. Lastly, we discuss the role of inflammation in age-related decline and in frailty. Future research directions are proposed, including identifying causal pathways among inflammatory markers, disability, and frailty. A better understanding of immunological functioning in late life may help unlock novel ways to promote successful aging. PMID:22500268

  1. Efficacy of Female Rat Models in Translational Cardiovascular Aging Research

    PubMed Central

    Rice, K. M.; Fannin, J. C.; Gillette, C.; Blough, E. R.

    2014-01-01

    Cardiovascular disease is the leading cause of death in women in the United States. Aging is a primary risk factor for the development of cardiovascular disease as well as cardiovascular-related morbidity and mortality. Aging is a universal process that all humans undergo; however, research in aging is limited by cost and time constraints. Therefore, most research in aging has been done in primates and rodents; however it is unknown how well the effects of aging in rat models translate into humans. To compound the complication of aging gender has also been indicated as a risk factor for various cardiovascular diseases. This review addresses the systemic pathophysiology of the cardiovascular system associated with aging and gender for aging research with regard to the applicability of rat derived data for translational application to human aging. PMID:25610649

  2. Age and gender specific biokinetic model for strontium in humans.

    PubMed

    Shagina, N B; Tolstykh, E I; Degteva, M O; Anspaugh, L R; Napier, B A

    2015-03-01

    A biokinetic model for strontium in humans is necessary for quantification of internal doses due to strontium radioisotopes. The ICRP-recommended biokinetic model for strontium has limitations for use in a population study, because it is not gender specific and does not cover all age ranges. The extensive Techa River data set on (90)Sr in humans (tens of thousands of measurements) is a unique source of data on long-term strontium retention for men and women of all ages at intake. These, as well as published data, were used for evaluation of age- and gender-specific parameters for a new compartment biokinetic model for strontium (Sr-AGe model). The Sr-AGe model has a similar structure to the ICRP model for the alkaline earth elements. The following parameters were mainly re-evaluated: gastrointestinal absorption and parameters related to the processes of bone formation and resorption defining calcium and strontium transfers in skeletal compartments. The Sr-AGe model satisfactorily describes available data sets on strontium retention for different kinds of intake (dietary and intravenous) at different ages (0-80 years old) and demonstrates good agreement with data sets for different ethnic groups. The Sr-AGe model can be used for dose assessment in epidemiological studies of general populations exposed to ingested strontium radioisotopes. PMID:25574605

  3. Age and gender specific biokinetic model for strontium in humans

    SciTech Connect

    Shagina, N. B.; Tolstykh, E. I.; Degteva, M. O.; Anspaugh, L. R.; Napier, Bruce A.

    2015-03-01

    A biokinetic model for strontium in humans is necessary for quantification of internal doses due to strontium radioisotopes. The ICRP-recommended biokinetic model for strontium has limitation for use in a population study, because it is not gender specific and does not cover all age ranges. The extensive Techa River data set on 90Sr in humans (tens of thousands of measurements) is a unique source of data on long-term strontium retention for men and women of all ages at intake. These, as well as published data, were used for evaluation of age- and gender-specific parameters for a new compartment biokinetic model for strontium (Sr-AGe model). The Sr-AGe model has similar structure as the ICRP model for the alkaline earth elements. The following parameters were mainly reevaluated: gastro-intestinal absorption and parameters related to the processes of bone formation and resorption defining calcium and strontium transfers in skeletal compartments. The Sr-AGe model satisfactorily describes available data sets on strontium retention for different kinds of intake (dietary and intravenous) at different ages (0–80 years old) and demonstrates good agreement with data sets for different ethnic groups. The Sr-AGe model can be used for dose assessment in epidemiological studies of general population exposed to ingested strontium radioisotopes.

  4. An integrated modeling approach to age invariant face recognition

    NASA Astrophysics Data System (ADS)

    Alvi, Fahad Bashir; Pears, Russel

    2015-03-01

    This Research study proposes a novel method for face recognition based on Anthropometric features that make use of an integrated approach comprising of a global and personalized models. The system is aimed to at situations where lighting, illumination, and pose variations cause problems in face recognition. A Personalized model covers the individual aging patterns while a Global model captures general aging patterns in the database. We introduced a de-aging factor that de-ages each individual in the database test and training sets. We used the k nearest neighbor approach for building a personalized model and global model. Regression analysis was applied to build the models. During the test phase, we resort to voting on different features. We used FG-Net database for checking the results of our technique and achieved 65 percent Rank 1 identification rate.

  5. A network model of human aging: Limits, errors, and information

    NASA Astrophysics Data System (ADS)

    Farrell, Spencer; Mitnitski, Arnold; Rockwood, Kenneth; Rutenberg, Andrew

    The Frailty Index (FI) quantifies human aging using the fraction of accumulated age-related deficits. The FI correlates strongly with mortality and accumulates non-linearly and stochastically with age. Clinical data shows a nearly universal limit of FI <= 0 . 7 . We computationally model an aging population using a network model of interacting deficits. Deficits damage and repair at rates that depend upon the average damage of connected nodes. The model is parametrized to fit clinical data. We find that attribution errors, especially false negative, allow the model to recover the frailty limit. Mutual information allows us to assess how well the FI can predict mortality. Mutual information provides a non-parametric measure of how the FI predicts mortality. We find that attribution errors have a small effect on the mutual information when many deficits are included in the model. The mutual information of our model and of the clinical data are comparable.

  6. Numerical solution of the Penna model of biological aging with age-modified mutation rate.

    PubMed

    Magdoń-Maksymowicz, M S; Maksymowicz, A Z

    2009-06-01

    In this paper we present results of numerical calculation of the Penna bit-string model of biological aging, modified for the case of a -dependent mutation rate m(a), where a is the parent's age. The mutation rate m(a) is the probability per bit of an extra bad mutation introduced in offspring inherited genome. We assume that m(a) increases with age a. As compared with the reference case of the standard Penna model based on a constant mutation rate m , the dynamics of the population growth shows distinct changes in age distribution of the population. Here we concentrate on mortality q(a), a fraction of items eliminated from the population when we go from age (a) to (a+1) in simulated transition from time (t) to next time (t+1). The experimentally observed q(a) dependence essentially follows the Gompertz exponential law for a above the minimum reproduction age. Deviation from the Gompertz law is however observed for the very old items, close to the maximal age. This effect may also result from an increase in mutation rate m with age a discussed in this paper. The numerical calculations are based on analytical solution of the Penna model, presented in a series of papers by Coe et al. [J. B. Coe, Y. Mao, and M. E. Cates, Phys. Rev. Lett. 89, 288103 (2002)]. Results of the numerical calculations are supported by the data obtained from computer simulation based on the solution by Coe et al. PMID:19658536

  7. An Age-Graded Model for Career Development Education.

    ERIC Educational Resources Information Center

    Tuckman, Bruce W.

    This paper presents a career developmental model covering the ages of 5 to 18. Career development education includes experiences which facilitate self-awareness, career-awareness and career decision-making. Before choosing a model for career development, it is necessary to decide on a model for child development. The model developed here borrows…

  8. Lithium battery aging model based on Dakin's degradation approach

    NASA Astrophysics Data System (ADS)

    Baghdadi, Issam; Briat, Olivier; Delétage, Jean-Yves; Gyan, Philippe; Vinassa, Jean-Michel

    2016-09-01

    This paper proposes and validates a calendar and power cycling aging model for two different lithium battery technologies. The model development is based on previous SIMCAL and SIMSTOCK project data. In these previous projects, the effect of the battery state of charge, temperature and current magnitude on aging was studied on a large panel of different battery chemistries. In this work, data are analyzed using Dakin's degradation approach. In fact, the logarithms of battery capacity fade and the increase in resistance evolves linearly over aging. The slopes identified from straight lines correspond to battery aging rates. Thus, a battery aging rate expression function of aging factors was deduced and found to be governed by Eyring's law. The proposed model simulates the capacity fade and resistance increase as functions of the influencing aging factors. Its expansion using Taylor series was consistent with semi-empirical models based on the square root of time, which are widely studied in the literature. Finally, the influence of the current magnitude and temperature on aging was simulated. Interestingly, the aging rate highly increases with decreasing and increasing temperature for the ranges of -5 °C-25 °C and 25 °C-60 °C, respectively.

  9. A comprehensive approach to age-dependent dosimetric modeling

    SciTech Connect

    Leggett, R.W.; Cristy, M.; Eckerman, K.F.

    1986-01-01

    In the absence of age-specific biokinetic models, current retention models of the International Commission on Radiological Protection (ICRP) frequently are used as a point of departure for evaluation of exposures to the general population. These models were designed and intended for estimation of long-term integrated doses to the adult worker. Their format and empirical basis preclude incorporation of much valuable physiological information and physiologically reasonable assumptions that could be used in characterizing the age-specific behavior of radioelements in humans. In this paper we discuss a comprehensive approach to age-dependent dosimetric modeling in which consideration is given not only to changes with age in masses and relative geometries of body organs and tissues but also to best available physiological and radiobiological information relating to the age-specific biobehavior of radionuclides. This approach is useful in obtaining more accurate estimates of long-term dose commitments as a function of age at intake, but it may be particularly valuable in establishing more accurate estimates of dose rate as a function of age. Age-specific dose rates are needed for a proper analysis of the potential effects on estimates or risk of elevated dose rates per unit intake in certain stages of life, elevated response per unit dose received during some stages of life, and age-specific non-radiogenic competing risks.

  10. Nutraceutical Interventions for Promoting Healthy Aging in Invertebrate Models

    PubMed Central

    Dong, Yuqing; Guha, Sujay; Sun, Xiaoping; Cao, Min; Wang, Xiaoxia; Zou, Sige

    2012-01-01

    Aging is a complex and inevitable biological process that is associated with numerous chronically debilitating health effects. Development of effective interventions for promoting healthy aging is an active but challenging area of research. Mechanistic studies in various model organisms, noticeably two invertebrates, Caenorhabditis elegans and Drosophila melanogaster, have identified many genes and pathways as well as dietary interventions that modulate lifespan and healthspan. These studies have shed light on some of the mechanisms involved in aging processes and provide valuable guidance for developing efficacious aging interventions. Nutraceuticals made from various plants contain a significant amount of phytochemicals with diverse biological activities. Phytochemicals can modulate many signaling pathways that exert numerous health benefits, such as reducing cancer incidence and inflammation, and promoting healthy aging. In this paper, we outline the current progress in aging intervention studies using nutraceuticals from an evolutionary perspective in invertebrate models. PMID:22991584

  11. Modeling the brain morphology distribution in the general aging population

    NASA Astrophysics Data System (ADS)

    Huizinga, W.; Poot, D. H. J.; Roshchupkin, G.; Bron, E. E.; Ikram, M. A.; Vernooij, M. W.; Rueckert, D.; Niessen, W. J.; Klein, S.

    2016-03-01

    Both normal aging and neurodegenerative diseases such as Alzheimer's disease cause morphological changes of the brain. To better distinguish between normal and abnormal cases, it is necessary to model changes in brain morphology owing to normal aging. To this end, we developed a method for analyzing and visualizing these changes for the entire brain morphology distribution in the general aging population. The method is applied to 1000 subjects from a large population imaging study in the elderly, from which 900 were used to train the model and 100 were used for testing. The results of the 100 test subjects show that the model generalizes to subjects outside the model population. Smooth percentile curves showing the brain morphology changes as a function of age and spatiotemporal atlases derived from the model population are publicly available via an interactive web application at agingbrain.bigr.nl.

  12. Econometric model for age- and population-dependent radiation exposures

    SciTech Connect

    Sandquist, G.M.; Slaughter, D.M. ); Rogers, V.C.

    1991-01-01

    The economic impact associated with ionizing radiation exposures in a given human population depends on numerous factors including the individual's mean economic status as a function age, the age distribution of the population, the future life expectancy at each age, and the latency period for the occurrence of radiation-induced health effects. A simple mathematical model has been developed that provides an analytical methodology for estimating the societal econometrics associated with radiation effects are to be assessed and compared for economic evaluation.

  13. Probabilistically Constraining Age-Depth-Models of Glaciogenic Sediments

    NASA Astrophysics Data System (ADS)

    Werner, J.; van der Bilt, W.; Tingley, M.

    2015-12-01

    Reconstructions of the late-Holocene climate rely heavily upon proxies that are assumed to be accurately dated by layer counting. All of these proxies, such as measurements of tree rings, ice cores, and varved lake sediments do carry some inherent dating uncertainty that is not always fully accounted for. Considerable advances could be achieved if time uncertainties were recognized and correctly modeled, also for proxies commonly treated as free of age model errors. Current approaches for accounting for time uncertainty are generally limited to repeating the reconstruction using each one of an ensemble of age models, thereby inflating the final estimated uncertainty - in effect, each possible age model is given equal weighting. Uncertainties can be reduced by exploiting the inferred space-time covariance structure of the climate to re-weight the possible age models. Werner and Tingley (2015) demonstrated how Bayesian hierarchical climate reconstruction models can be augmented to account for time-uncertain proxies. In their method, probabilities associated with the age models are formally updated within the Bayesian framework, thereby reducing uncertainties. Numerical experiments (Werner and Tingley 2015) show that updating the age model probabilities decreases uncertainty in the resulting reconstructions, as compared with the current de facto standard of sampling over all age models, provided there is sufficient information from other data sources in the spatial region of the time-uncertain proxy. We show how this novel method can be applied to high resolution, sub-annually sampled lacustrine sediment records to constrain their respective age depth models. The results help to quantify the signal content and extract the regionally representative signal. The single time series can then be used as the basis for a reconstruction of glacial activity. van der Bilt et al. in prep. Werner, J.P. and Tingley, M.P. Clim. Past (2015)

  14. Selection Experiments in the Penna Model for Biological Aging

    NASA Astrophysics Data System (ADS)

    Medeiros, G.; Idiart, M. A.; de Almeida, R. M. C.

    We consider the Penna model for biological aging to investigate correlations between early fertility and late life survival rates in populations at equilibrium. We consider inherited initial reproduction ages together with a reproduction cost translated in a probability that mother and offspring die at birth, depending on the mother age. For convenient sets of parameters, the equilibrated populations present genetic variability in what regards both genetically programmed death age and initial reproduction age. In the asexual Penna model, a negative correlation between early life fertility and late life survival rates naturally emerges in the stationary solutions. In the sexual Penna model, selection experiments are performed where individuals are sorted by initial reproduction age from the equilibrated populations and the separated populations are evolved independently. After a transient, a negative correlation between early fertility and late age survival rates also emerges in the sense that populations that start reproducing earlier present smaller average genetically programmed death age. These effects appear due to the age structure of populations in the steady state solution of the evolution equations. We claim that the same demographic effects may be playing an important role in selection experiments in the laboratory.

  15. 14C-age tracers in global ocean circulation models

    NASA Astrophysics Data System (ADS)

    Koeve, W.; Wagner, H.; Kähler, P.; Oschlies, A.

    2015-07-01

    The natural abundance of 14C in total CO2 dissolved in seawater (DIC) is a property applied to evaluate the water age structure and circulation in the ocean and in ocean models. In this study we use three different representations of the global ocean circulation augmented with a suite of idealised tracers to study the potential and limitations of using natural 14C to determine water age, which is the time elapsed since a body of water has been in contact with the atmosphere. We find that, globally, bulk 14C-age is dominated by two equally important components, one associated with ageing, i.e. the time component of circulation, and one associated with a "preformed 14C-age". The latter quantity exists because of the slow and incomplete atmosphere-ocean equilibration of 14C particularly in high latitudes where many water masses form. In the ocean's interior, preformed 14C-age behaves like a passive tracer. The relative contribution of the preformed component to bulk 14C-age varies regionally within a given model, but also between models. Regional variability in the Atlantic Ocean is associated with the mixing of waters with very different end members of preformed 14C-age. Here, variations in the preformed component over space and time mask the circulation component to an extent that its patterns are not detectable from bulk 14C-age. Between models, the variability of preformed 14C-age can also be considerable (factor of 2), related to the combination of physical model parameters, which influence circulation dynamics or gas exchange. The preformed component was found to be very sensitive to gas exchange and moderately sensitive to ice cover. In our model evaluation, the choice of the gas-exchange constant from within the currently accepted range of uncertainty had such a strong influence on preformed and bulk 14C-age that if model evaluation would be based on bulk 14C-age, it could easily impair the evaluation and tuning of a model's circulation on global and regional

  16. Multiscale Concrete Modeling of Aging Degradation

    SciTech Connect

    Hammi, Yousseff; Gullett, Philipp; Horstemeyer, Mark F.

    2015-07-31

    In this work a numerical finite element framework is implemented to enable the integration of coupled multiscale and multiphysics transport processes. A User Element subroutine (UEL) in Abaqus is used to simultaneously solve stress equilibrium, heat conduction, and multiple diffusion equations for 2D and 3D linear and quadratic elements. Transport processes in concrete structures and their degradation mechanisms are presented along with the discretization of the governing equations. The multiphysics modeling framework is theoretically extended to the linear elastic fracture mechanics (LEFM) by introducing the eXtended Finite Element Method (XFEM) and based on the XFEM user element implementation of Giner et al. [2009]. A damage model that takes into account the damage contribution from the different degradation mechanisms is theoretically developed. The total contribution of damage is forwarded to a Multi-Stage Fatigue (MSF) model to enable the assessment of the fatigue life and the deterioration of reinforced concrete structures in a nuclear power plant. Finally, two examples are presented to illustrate the developed multiphysics user element implementation and the XFEM implementation of Giner et al. [2009].

  17. 14C-age tracers in global ocean circulation models

    NASA Astrophysics Data System (ADS)

    Koeve, W.; Wagner, H.; Kähler, P.; Oschlies, A.

    2014-10-01

    The natural abundance of 14C in total CO2 dissolved in seawater is a property applied to evaluate the water age structure and circulation in the ocean and in ocean models. In this study we use three different representations of the global ocean circulation augmented with a suite of idealised tracers to study the potential and limitations of using natural 14C to determine water age, the time elapsed since a body of water had contact with the atmosphere. We find that, globally, bulk 14C-age is dominated by two equally important components, one associated with aging, i.e. the time component of circulation and one associated with a "preformed 14C-age". This latter quantity exists because of the slow and incomplete atmosphere/ocean equilibration of 14C in particular in high latitudes where many water masses form. The relative contribution of the preformed component to bulk 14C-age varies regionally within a given model, but also between models. Regional variability, e.g. in the Atlantic Ocean is associated with the mixing of waters with very different end members of preformed 14C-age. In the Atlantic, variations in the preformed component over space and time mask the circulation component to an extent that its patterns are not detectable from bulk 14C-age alone. Between models the variability of age can also be considerable (factor of 2), related to the combinations of physical model parameters, which influence circulation dynamics, and gas exchange in the models. The preformed component was found to be very sensitive to gas exchange and moderately sensitive to ice cover. In our model evaluation exercise, the choice of the gas exchange constant from within the current range of uncertainty had such a strong influence on preformed and bulk 14C-age that if model evaluation would be based on bulk 14C-age it could easily impair the evaluation and tuning of a models circulation on global and regional scales. Based on the results of this study, we propose that considering

  18. Aging mechanism in model Pickering emulsion.

    PubMed

    Fouilloux, Sarah; Malloggi, Florent; Daillant, Jean; Thill, Antoine

    2016-01-21

    We study the stability of a model Pickering emulsion system using fluorinated oil and functionalized silica nanoparticles. A special counter-flow microfluidic set-up was used to prepare monodisperse oil droplets in water. The wettability of the monodisperse silica nanoparticles (NPs) could be tuned by surface grafting and the surface coverage of the droplets was controlled using the microfluidic setup. For surface coverage as low as 23%, we observed a regime of Pickering emulsion stability where the surface coverage of emulsion droplets of constant size increases with time, coexisting with an excess of oil phase. Our results demonstrate that the previously observed limited coalescence regime where surface coverage tends to control the average size of the final droplets must be put in a broader perspective. PMID:26549639

  19. Modeling Age-Friendly Environment, Active Aging, and Social Connectedness in an Emerging Asian Economy.

    PubMed

    Lai, Ming-Ming; Lein, Shi-Ying; Lau, Siok-Hwa; Lai, Ming-Ling

    2016-01-01

    This paper empirically tested eight key features of WHO guidelines to age-friendly community by surveying 211 informal caregivers and 402 self-care adults (aged 45 to 85 and above) in Malaysia. We examined the associations of these eight features with active aging and social connectedness through exploratory and confirmatory factor analyses. A structural model with satisfactory goodness-of-fit indices (CMIN/df = 1.11, RMSEA = 0.02, NFI = 0.97, TLI = 1.00, CFI = 1.00, and GFI = 0.96) indicates that transportation and housing, community support and health services, and outdoor spaces and buildings are statistically significant in creating an age-friendly environment. We found a statistically significant positive relationship between an age-friendly environment and active aging. This relationship is mediated by social connectedness. The results indicate that built environments such as accessible public transportations and housing, affordable and accessible healthcare services, and elderly friendly outdoor spaces and buildings have to be put into place before social environment in building an age-friendly environment. Otherwise, the structural barriers would hinder social interactions for the aged. The removal of the environmental barriers and improved public transportation services provide short-term solutions to meet the varied and growing needs of the older population. PMID:27293889

  20. Modeling Age-Friendly Environment, Active Aging, and Social Connectedness in an Emerging Asian Economy

    PubMed Central

    Lai, Ming-Ming; Lein, Shi-Ying; Lau, Siok-Hwa; Lai, Ming-Ling

    2016-01-01

    This paper empirically tested eight key features of WHO guidelines to age-friendly community by surveying 211 informal caregivers and 402 self-care adults (aged 45 to 85 and above) in Malaysia. We examined the associations of these eight features with active aging and social connectedness through exploratory and confirmatory factor analyses. A structural model with satisfactory goodness-of-fit indices (CMIN/df = 1.11, RMSEA = 0.02, NFI = 0.97, TLI = 1.00, CFI = 1.00, and GFI = 0.96) indicates that transportation and housing, community support and health services, and outdoor spaces and buildings are statistically significant in creating an age-friendly environment. We found a statistically significant positive relationship between an age-friendly environment and active aging. This relationship is mediated by social connectedness. The results indicate that built environments such as accessible public transportations and housing, affordable and accessible healthcare services, and elderly friendly outdoor spaces and buildings have to be put into place before social environment in building an age-friendly environment. Otherwise, the structural barriers would hinder social interactions for the aged. The removal of the environmental barriers and improved public transportation services provide short-term solutions to meet the varied and growing needs of the older population. PMID:27293889

  1. Exact solution of an evolutionary model without aging

    NASA Astrophysics Data System (ADS)

    Onody, Roberto N.; de Medeiros, Nazareno G. F.

    1999-09-01

    We introduce an age-structured asexual population model containing all the relevant features of evolutionary aging theories. Beneficial as well as deleterious mutations, heredity, and arbitrary fecundity are present and managed by natural selection. An exact solution without aging is found. We show that fertility is associated with generalized forms of the Fibonacci sequence, while mutations and natural selection are merged into an integral equation which is solved by Fourier series. Average survival probabilities and Malthusian growth exponents are calculated and indicate that the system may exhibit mutational meltdown. The relevance of the model in the context of fissile reproduction groups like many protozoa and coelenterates is discussed.

  2. The Development of Small Primate Models for Aging Research

    PubMed Central

    Fischer, Kathleen E.; Austad, Steven N.

    2015-01-01

    Nonhuman primate (NHP) aging research has traditionally relied mainly on the rhesus macaque. But the long lifespan, low reproductive rate, and relatively large body size of macaques and related Old World monkeys make them less than ideal models for aging research. Manifold advantages would attend the use of smaller, more rapidly developing, shorter-lived NHP species in aging studies, not the least of which are lower cost and the ability to do shorter research projects. Arbitrarily defining “small” primates as those weighing less than 500 g, we assess small, relatively short-lived species among the prosimians and callitrichids for suitability as models for human aging research. Using the criteria of availability, knowledge about (and ease of) maintenance, the possibility of genetic manipulation (a hallmark of 21st century biology), and similarities to humans in the physiology of age-related changes, we suggest three species—two prosimians (Microcebus murinus and Galago senegalensis) and one New World monkey (Callithrix jacchus)—that deserve scrutiny for development as major NHP models for aging studies. We discuss one other New World monkey group, Cebus spp., that might also be an effective NHP model of aging as these species are longer-lived for their body size than any primate except humans. PMID:21411860

  3. Dynamical Masses Demonstrate the Discordant Model Ages for Upper Scorpius

    NASA Astrophysics Data System (ADS)

    Rizzuto, Aaron C.; Ireland, Michael; Kraus, Adam L.; Dupuy, Trent J.

    2016-01-01

    We present the results of a long term orbit monitoring program, using sparse aperture masking observations taken with NIRC2 on the Keck-II telescope, of seven G to M-type members of the Upper Scorpius subgroup of the Sco-Cen OB association. We present astrometry and derived orbital elements of the binary systems we have monitored, and also determine the age, component masses, distance and reddening for each system using the orbital solutions and multi-band photometry, including Hubble Space Telescope photometry, and a Bayesian fitting procedure. We find that the models can be forced into agreement with any individual system by assuming an age, but that ageis not consistent across the mass range of our sample. The G-type binary systems in our sample have model ages of ~11.5 Myr, which is consistent with the latest age estimates for Upper Scorpius, while the M-type binary systems have significantly younger model ages of ~7 Myr. Based on our fits to the data, this age discrepancy in the models corresponds to a luminosity under-prediction of 0.8-0.15 dex, or equivalently an effective temperature over-prediction of 100-300 K for M-type stars at a given premain-sequence age.

  4. The heuristic value of redundancy models of aging.

    PubMed

    Boonekamp, Jelle J; Briga, Michael; Verhulst, Simon

    2015-11-01

    Molecular studies of aging aim to unravel the cause(s) of aging bottom-up, but linking these mechanisms to organismal level processes remains a challenge. We propose that complementary top-down data-directed modelling of organismal level empirical findings may contribute to developing these links. To this end, we explore the heuristic value of redundancy models of aging to develop a deeper insight into the mechanisms causing variation in senescence and lifespan. We start by showing (i) how different redundancy model parameters affect projected aging and mortality, and (ii) how variation in redundancy model parameters relates to variation in parameters of the Gompertz equation. Lifestyle changes or medical interventions during life can modify mortality rate, and we investigate (iii) how interventions that change specific redundancy parameters within the model affect subsequent mortality and actuarial senescence. Lastly, as an example of data-directed modelling and the insights that can be gained from this, (iv) we fit a redundancy model to mortality patterns observed by Mair et al. (2003; Science 301: 1731-1733) in Drosophila that were subjected to dietary restriction and temperature manipulations. Mair et al. found that dietary restriction instantaneously reduced mortality rate without affecting aging, while temperature manipulations had more transient effects on mortality rate and did affect aging. We show that after adjusting model parameters the redundancy model describes both effects well, and a comparison of the parameter values yields a deeper insight in the mechanisms causing these contrasting effects. We see replacement of the redundancy model parameters by more detailed sub-models of these parameters as a next step in linking demographic patterns to underlying molecular mechanisms. PMID:26362219

  5. Invertebrates as model organisms for research on aging biology

    PubMed Central

    Murthy, Mahadev; Ram, Jeffrey L.

    2015-01-01

    Invertebrate model systems, such as nematodes and fruit flies, have provided valuable information about the genetics and cellular biology involved in aging. However, limitations of these simple, genetically tractable organisms suggest the need for other model systems, some of them invertebrate, to facilitate further advances in the understanding of mechanisms of aging and longevity in mammals, including humans. This paper introduces 10 review articles about the use of invertebrate model systems for the study of aging by authors who participated in an ‘NIA-NIH symposium on aging in invertebrate model systems’ at the 2013 International Congress for Invertebrate Reproduction and Development. In contrast to the highly derived characteristics of nematodes and fruit flies as members of the superphylum Ecdysozoa, cnidarians, such as Hydra, are more ‘basal’ organisms that have a greater number of genetic orthologs in common with humans. Moreover, some other new model systems, such as the urochordate Botryllus schlosseri, the tunicate Ciona, and the sea urchins (Echinodermata) are members of the Deuterostomia, the same superphylum that includes all vertebrates, and thus have mechanisms that are likely to be more closely related to those occurring in humans. Additional characteristics of these new model systems, such as the recent development of new molecular and genetic tools and a more similar pattern to humans of regeneration and stem cell function suggest that these new model systems may have unique advantages for the study of mechanisms of aging and longevity. PMID:26241448

  6. Age-related Cardiac Disease Model of Drosophila

    PubMed Central

    Ocorr, Karen; Akasaka, Takeshi; Bodmer, Rolf

    2007-01-01

    We have begun to study the genetic basis of deterioration of cardiac function in the fruit fly Drosophila melanogaster as an age-related cardiac disease model. For this purpose we have developed heart function assays in Drosophila and found that the fly's cardiac performance, as that of the human heart, deteriorates with age: aging fruit flies exhibit a progressive increase in electrical pacing-induced heart failure as well as in arrhythmias. The insulin receptor and associated pathways have a dramatic and heart-autonomous influence on age-related cardiac performance in flies, suggestive of potentially similar mechanisms in regulating cardiac aging in vertebrates. Compromised KCNQ and KATP ion channel functions also seem to contribute to the decline in heart performance in aging flies, suggesting that the corresponding vertebrate gene functions may similarly decline with age, in addition to their conserved role in protecting against arrhythmias and hypoxia/ischemia, respectively. The fly heart is thus emerging as a promising genetic model for studying the age-dependent decline in organ function. PMID:17125816

  7. Identification of the het-r vegetative incompatibility gene of Podospora anserina as a member of the fast evolving HNWD gene family.

    PubMed

    Chevanne, Damien; Bastiaans, Eric; Debets, Alfons; Saupe, Sven J; Clavé, Corinne; Paoletti, Mathieu

    2009-02-01

    In fungi, vegetative incompatibility is a conspecific non-self recognition mechanism that restricts formation of viable heterokaryons when incompatible alleles of specific het loci interact. In Podospora anserina, three non-allelic incompatibility systems have been genetically defined involving interactions between het-c and het-d, het-c and het-e, het-r and het-v. het-d and het-e are paralogues belonging to the HNWD gene family that encode proteins of the STAND class. HET-D and HET-E proteins comprise an N-terminal HET effector domain, a central GTP binding site and a C-terminal WD repeat domain constituted of tandem repeats of highly conserved WD40 repeat units that define the specificity of alleles during incompatibility. The WD40 repeat units of the members of this HNWD family are undergoing concerted evolution. By combining genetic analysis and gain of function experiments, we demonstrate that an additional member of this family, HNWD2, corresponds to the het-r non-allelic incompatibility gene. As for het-d and het-e, allele specificity at the het-r locus is determined by the WD repeat domain. Natural isolates show allelic variation for het-r. PMID:19137300

  8. Deletion of the MED13 and CDK8 subunits of the Mediator improves the phenotype of a long-lived respiratory deficient mutant of Podospora anserina.

    PubMed

    Humbert, Adeline; Bovier, Elodie; Sellem, Carole H; Sainsard-Chanet, Annie

    2015-09-01

    In Podospora anserina, the loss of function of the cytochrome segment of the mitochondrial respiratory chain is viable. This is due to the presence in this organism, as in most filamentous fungi, of an alternative respiratory oxidase (AOX) that provides a bypass to the cytochrome pathway. However mutants lacking a functional cytochrome pathway present multiple phenotypes including poorly colored thin mycelium and slow growth. In a large genetic screen based on the improvement of these phenotypes, we isolated a large number of independent suppressor mutations. Most of them led to the constitutive overexpression of the aox gene. In this study, we characterize a new suppressor mutation that does not affect the production of AOX. It is a loss-of-function mutation in the gene encoding the MED13 subunit of the kinase module of the Mediator complex. Inactivation of the cdk8 gene encoding another subunit of the same module also results in partial suppression of a cytochrome-deficient mutant. Analysis of strains lacking the MED13 or CDK8 subunits points to the importance of these subunits as regulators involved in diverse physiological processes such as growth, longevity and sexual development. Interestingly, transcriptional analyses indicate that in P. anserina, loss of the respiratory cytochrome pathway results in the up-regulation of glycolysis-related genes revealing a new type of retrograde regulation. The loss of MED13 augments the up-regulation of some of these genes. PMID:26231682

  9. Incomplete penetrance and variable expressivity of a growth defect as a consequence of knocking out two K(+) transporters in the euascomycete fungus Podospora anserina.

    PubMed Central

    Lalucque, Hervé; Silar, Philippe

    2004-01-01

    We describe an example of incomplete penetrance and variable expressivity in the filamentous fungus Podospora anserina, two genetic properties classically associated with mutations in more complex organisms, such as green plants and animals. We show that the knockouts of two TRK-related K(+) transporters of this ascomycete present variability in their phenotype that cannot be attributed to fluctuations of the genetic background or the environment. Thalli of the knockout strains derived from independent monokaryotic ascospores or from a single monokaryotic ascospore and cultivated under standard growth conditions may or may not present impaired growth. When impaired, thalli exhibit a range of phenotypes. Environmental conditions control expressivity to a large extent and penetrance to a low extent. Restoration of functional potassium transport by heterologous expression of K(+) transporters from Neurospora crassa abolishes or strongly diminishes the growth impairment. These data show that incomplete penetrance and variable expressivity can be an intrinsic property of a single Mendelian loss-of-function mutation. They also show that such variability in the expression of a mutant phenotype can be promoted by a phenomenon not obviously related to the well-known chromatin structure modifications, i.e., potassium transport. They provide a framework to understand human channelopathies with similar properties. PMID:15020412

  10. eEF1A Controls ascospore differentiation through elevated accuracy, but controls longevity and fruiting body formation through another mechanism in Podospora anserina.

    PubMed Central

    Silar, P; Lalucque, H; Haedens, V; Zickler, D; Picard, M

    2001-01-01

    Antisuppressor mutations in the eEF1A gene of Podospora anserina were previously shown to impair ascospore formation, to drastically increase life span, and to permit the development of the Crippled Growth degenerative process. Here, we show that eEF1A controls ascospore formation through accuracy level maintenance. Examination of antisuppressor mutant perithecia reveals two main cytological defects, mislocalization of spindle and nuclei and nuclear death. Antisuppression levels are shown to be highly dependent upon both the mutation site and the suppressor used, precluding any correlation between antisuppression efficiency and severity of the sporulation impairment. Nevertheless, severity of ascospore differentiation defect is correlated with resistance to paromomycin. We also show that eEF1A controls fruiting body formation and longevity through a mechanism(s) different from accuracy control. In vivo, GFP tagging of the protein in a way that partly retains its function confirmed earlier cytological observation; i.e., this factor is mainly diffuse within the cytosol, but may transiently accumulate within nuclei or in defined regions of the cytoplasm. These data emphasize the fact that the translation apparatus exerts a global regulatory control over cell physiology and that eEF1A is one of the key factors involved in this monitoring. PMID:11514440

  11. A homologue of the yeast SHE4 gene is essential for the transition between the syncytial and cellular stages during sexual reproduction of the fungus Podospora anserina.

    PubMed Central

    Berteaux-Lecellier, V; Zickler, D; Debuchy, R; Panvier-Adoutte, A; Thompson-Coffe, C; Picard, M

    1998-01-01

    The Podospora anserina cro1 gene was identified as a gene required for sexual sporulation. Crosses homozygous for the cro1-1 mutation yield fruiting bodies which produce few asci due to the formation of giant plurinucleate cells instead of dikaryotic cells after fertilization. This defect does not impair karyogamy, but meioses of the resultant polyploid nuclei are most often abortive. Cytological studies suggest that the primary defect of the mutant is its inability to form septa between the daughter nuclei after each mitosis, a step specific for normal dikaryotic cell divisions. The cro1-1 mutant would thus be unable to leave the syncytial vegetative state while abiding by the meiotic programme. cro1-1 also shows defects in ascospore germination and growth rate. GFP-tagging of the CRO1 protein reveals that it is a cytosolic protein mainly expressed at the beginning of the dikaryotic stage and at the time of ascospore maturation. The CRO1 protein exhibits significant similarity to the SHE4 protein, which is required for asymmetric mating-type switching in budding yeast cells. Thus, a gene involved in asymmetric cell divisions in a unicellular organism plays a key role at the transition between the syncytial (vegetative) state and the cellular (sexual) state in a filamentous fungus. PMID:9482722

  12. ami1, an orthologue of the Aspergillus nidulans apsA gene, is involved in nuclear migration events throughout the life cycle of Podospora anserina.

    PubMed Central

    Graïa, F; Berteaux-Lecellier, V; Zickler, D; Picard, M

    2000-01-01

    The Podospora anserina ami1-1 mutant was identified as a male-sterile strain. Microconidia (which act as male gametes) form, but are anucleate. Paraphysae from the perithecium beaks are also anucleate when ami1-1 is used as the female partner in a cross. Furthermore, in crosses heterozygous for ami1-1, some crozier cells are uninucleate rather than binucleate. In addition to these nuclear migration defects, which occur at the transition between syncytial and cellular states, ami1-1 causes abnormal distribution of the nuclei in both mycelial filaments and asci. Finally, an ami1-1 strain bearing information for both mating types is unable to self-fertilize. The ami1 gene is an orthologue of the Aspergillus nidulans apsA gene, which controls nuclear positioning in filaments and during conidiogenesis (at the syncytial/cellular transition). The ApsA and AMI1 proteins display 42% identity and share structural features. The apsA gene complements some ami1-1 defects: it increases the percentage of nucleate microconidia and restores self-fertility in an ami1-1 mat+ (mat-) strain. The latter effect is puzzling, since in apsA null mutants sexual reproduction is quite normal. The functional differences between the two genes are discussed with respect to their possible history in these two fungi, which are very distant in terms of evolution. PMID:10835387

  13. Identification of six loci in which mutations partially restore peroxisome biogenesis and/or alleviate the metabolic defect of pex2 mutants in podospora.

    PubMed Central

    Ruprich-Robert, Gwenaël; Berteaux-Lecellier, Véronique; Zickler, Denise; Panvier-Adoutte, Arlette; Picard, Marguerite

    2002-01-01

    Peroxins (PEX) are proteins required for peroxisome biogenesis. Mutations in PEX genes cause lethal diseases in humans, metabolic defects in yeasts, and developmental disfunctions in plants and filamentous fungi. Here we describe the first large-scale screening for suppressors of a pex mutation. In Podospora anserina, pex2 mutants exhibit a metabolic defect [inability to grow on medium containing oleic acid (OA medium) as sole carbon source] and a developmental defect (inability to differentiate asci in homozygous crosses). Sixty-three mutations able to restore growth of pex2 mutants on OA medium have been analyzed. They fall in six loci (suo1 to suo6) and act as dominant, allele-nonspecific suppressors. Most suo mutations have pleiotropic effects in a pex2(+) background: formation of unripe ascospores (all loci except suo5 and suo6), impaired growth on OA medium (all loci except suo4 and suo6), or sexual defects (suo4). Using immunofluorescence and GFP staining, we show that peroxisome biogenesis is partially restored along with a low level of ascus differentiation in pex2 mutant strains carrying either the suo5 or the suo6 mutations. The data are discussed with respect to beta-oxidation of fatty acids, peroxisome biogenesis, and cell differentiation. PMID:12136013

  14. Structural and Biochemical Analyses of Glycoside Hydrolase Families 5 and 26 β-(1,4)-Mannanases from Podospora anserina Reveal Differences upon Manno-oligosaccharide Catalysis*

    PubMed Central

    Couturier, Marie; Roussel, Alain; Rosengren, Anna; Leone, Philippe; Stålbrand, Henrik; Berrin, Jean-Guy

    2013-01-01

    The microbial deconstruction of the plant cell wall is a key biological process that is of increasing importance with the development of a sustainable biofuel industry. The glycoside hydrolase families GH5 (PaMan5A) and GH26 (PaMan26A) endo-β-1,4-mannanases from the coprophilic ascomycete Podospora anserina contribute to the enzymatic degradation of lignocellulosic biomass. In this study, P. anserina mannanases were further subjected to detailed comparative analysis of their substrate specificities, active site organization, and transglycosylation capacity. Although PaMan5A displays a classical mode of action, PaMan26A revealed an atypical hydrolysis pattern with the release of mannotetraose and mannose from mannopentaose resulting from a predominant binding mode involving the −4 subsite. The crystal structures of PaMan5A and PaMan26A were solved at 1.4 and 2.85 Å resolution, respectively. Analysis of the PaMan26A structure supported strong interaction with substrate at the −4 subsite mediated by two aromatic residues Trp-244 and Trp-245. The PaMan26A structure appended to its family 35 carbohydrate binding module revealed a short and proline-rich rigid linker that anchored together the catalytic and the binding modules. PMID:23558681

  15. Active Ageing: An Empirical Approach to the WHO Model

    PubMed Central

    Paúl, Constança; Ribeiro, Oscar; Teixeira, Laetitia

    2012-01-01

    Background. In the beginning of the 21st century, the world summit on population taking place in Madrid approved active ageing, WHO (2002) as the main objective of health and social policies for old people. Few studies have been done on the scientific validity of the construct. This study aims to validate the construct of active ageing and test empirically the WHO (2002) model of Active Ageing in a sample of community-dwelling seniors. Methods. 1322 old people living in the community were interviewed using an extensive assessment protocol to measure WHO's determinants of active ageing and performed an exploratory factor analysis followed by a confirmatory factor analyses. Results. We did not confirm the active ageing model, as most of the groups of determinants are either not independent or not significant. We got to a six-factor model (health, psychological component, cognitive performance, social relationships, biobehavioural component, and personality) explaining 54.6% of total variance. Conclusion. The present paper shows that there are objective as well as subjective variables contributing to active ageing and that psychological variables seem to give a very important contribute to the construct. The profile of active ageing is expected to vary between contexts and cultures and can be used to guide specific community and individually based interventions. PMID:23193396

  16. Age-space-time CAR models in Bayesian disease mapping.

    PubMed

    Goicoa, T; Ugarte, M D; Etxeberria, J; Militino, A F

    2016-06-30

    Mortality counts are usually aggregated over age groups assuming similar effects of both time and region, yet the spatio-temporal evolution of cancer mortality rates may depend on changing age structures. In this paper, mortality rates are analyzed by region, time period and age group, and models including space-time, space-age, and age-time interactions are considered. The integrated nested Laplace approximation method, known as INLA, is adopted for model fitting and inference in order to reduce computing time in comparison with Markov chain Monte Carlo (McMC) methods. The methodology provides full posterior distributions of the quantities of interest while avoiding complex simulation techniques. The proposed models are used to analyze prostate cancer mortality data in 50 Spanish provinces over the period 1986-2010. The results reveal a decline in mortality since the late 1990s, particularly in the age group [65,70), probably because of the inclusion of the PSA (prostate-specific antigen) test and better treatment of early-stage disease. The decline is not clearly observed in the oldest age groups. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26814019

  17. Snow water equivalent modeling components in NewAge-JGrass

    NASA Astrophysics Data System (ADS)

    Formetta, G.; Kampf, S. K.; David, O.; Rigon, R.

    2014-05-01

    This paper presents a package of modified temperature-index-based snow water equivalent models as part of the hydrological modeling system NewAge-JGrass. Three temperature-based snow models are integrated into the NewAge-JGrass modeling system and use many of its components such as those for radiation balance (short wave radiation balance, SWRB), kriging (KRIGING), automatic calibration algorithms (particle swarm optimization) and tests of goodness of fit (NewAge-V), to build suitable modeling solutions (MS). Similarly to all the NewAge-JGrass components, the models can be executed both in raster and in vector mode. The simulation time step can be daily, hourly or sub-hourly, depending on user needs and availability of input data. The MS are applied on the Cache la Poudre River basin (CO, USA) using three test applications. First, daily snow water equivalent is simulated for three different measurement stations for two snow model formulations. Second, hourly snow water equivalent is simulated using all the three different snow model formulae. Finally, a raster mode application is performed to compute snow water equivalent maps for the whole Cache la Poudre Basin.

  18. Age Dependent Absolute Plate and Plume Motion Modeling

    NASA Astrophysics Data System (ADS)

    Heaton, D. E.; Koppers, A. A. P.

    2015-12-01

    Current absolute plate motion (APM) models from 80 - 0 Ma are constrained by the location of mantle plume related hotspot seamounts, in particular those of the Hawaiian-Emperor and Louisville seamount trails. Originally the 'fixed' hotspot hypothesis was developed to explain past plate motion based on linear age progressive intra-plate volcanism. However, now that 'moving' hotspots are accepted, it is becoming clear that APM models need to be corrected for individual plume motion vectors. For older seamount trails that were active between roughly 50 and 80 Ma the APM models that use 'fixed' hotspots overestimate the measured age progression in those trails, while APM models corrected for 'moving' hotspots underestimate those age progressions. These mismatches are due to both a lack of reliable ages in the older portions of both the Hawaii and Louisville seamount trails and insufficient APM modeling constraints from other seamount trails in the Pacific Basin. Seamounts are difficult to sample and analyze because many are hydrothermally altered and have low potassium concentrations. New 40Ar/39Ar Age results from International Ocean Drilling Project (IODP) Expedition 330 Sites U1372 (n=18), U1375 (n=3), U1376 (n=15) and U1377 (n=7) aid in constraining the oldest end of the Louisville Seamount trail. A significant observation in this study is that the age range recovered in the drill cores match the range of ages that were acquired on dredging cruises at the same seamounts (e.g. Koppers et al., 2011). This is important for determining the inception age of a seamount. The sections recovered from IODP EXP 330 are in-situ volcanoclastic breccia and lava flows. Comparing the seismic interpretations of Louisville guyots (Contreras-Reyes et al., 2010), Holes U1372, U1373 and U1374 penetrated the extrusive and volcanoclastic sections of the seamount. The ages obtained are consistent over stratigraphic intervals >100-450 m thick, providing evidence that these seamounts

  19. Mathematically modelling the dynamics of cholesterol metabolism and ageing.

    PubMed

    Morgan, A E; Mooney, K M; Wilkinson, S J; Pickles, N A; Mc Auley, M T

    2016-07-01

    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the UK. This condition becomes increasingly prevalent during ageing; 34.1% and 29.8% of males and females respectively, over 75 years of age have an underlying cardiovascular problem. The dysregulation of cholesterol metabolism is inextricably correlated with cardiovascular health and for this reason low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) are routinely used as biomarkers of CVD risk. The aim of this work was to use mathematical modelling to explore how cholesterol metabolism is affected by the ageing process. To do this we updated a previously published whole-body mathematical model of cholesterol metabolism to include an additional 96 mechanisms that are fundamental to this biological system. Additional mechanisms were added to cholesterol absorption, cholesterol synthesis, reverse cholesterol transport (RCT), bile acid synthesis, and their enterohepatic circulation. The sensitivity of the model was explored by the use of both local and global parameter scans. In addition, acute cholesterol feeding was used to explore the effectiveness of the regulatory mechanisms which are responsible for maintaining whole-body cholesterol balance. It was found that our model behaves as a hypo-responder to cholesterol feeding, while both the hepatic and intestinal pools of cholesterol increased significantly. The model was also used to explore the effects of ageing in tandem with three different cholesterol ester transfer protein (CETP) genotypes. Ageing in the presence of an atheroprotective CETP genotype, conferring low CETP activity, resulted in a 0.6% increase in LDL-C. In comparison, ageing with a genotype reflective of high CETP activity, resulted in a 1.6% increase in LDL-C. Thus, the model has illustrated the importance of CETP genotypes such as I405V, and their potential role in healthy ageing. PMID:27157786

  20. Justification of sexual reproduction by modified Penna model of ageing

    NASA Astrophysics Data System (ADS)

    Sá Martins, J. S.; Stauffer, D.

    2001-05-01

    We generalize the standard Penna bit-string model of biological ageing by assuming that each deleterious mutation diminishes the survival probability in every time interval by a small percentage. This effect is added to the usual lethal but age-dependent effect of the same mutation. We then find strong advantages or disadvantages of sexual reproduction (with males and females) compared to asexual cloning, depending on parameters.

  1. Age-dependent forest carbon sink: Estimation via inverse modeling

    NASA Astrophysics Data System (ADS)

    Zhou, Tao; Shi, Peijun; Jia, Gensuo; Dai, Yongjiu; Zhao, Xiang; Shangguan, Wei; Du, Ling; Wu, Hao; Luo, Yiqi

    2015-12-01

    Forests have been recognized to sequester a substantial amount of carbon (C) from the atmosphere. However, considerable uncertainty remains regarding the magnitude and time course of the C sink. Revealing the intrinsic relationship between forest age and C sink is crucial for reducing uncertainties in prediction of forest C sink potential. In this study, we developed a stepwise data assimilation approach to combine a process-based Terrestrial ECOsystem Regional model, observations from multiple sources, and stochastic sampling to inversely estimate carbon cycle parameters including carbon sink at different forest ages for evergreen needle-leaved forests in China. The new approach is effective to estimate age-dependent parameter of maximal light-use efficiency (R2 = 0.99) and, accordingly, can quantify a relationship between forest age and the vegetation and soil C sinks. The estimated ecosystem C sink increases rapidly with age, peaks at 0.451 kg C m-2 yr-1 at age 22 years (ranging from 0.421 to 0.465 kg C m-2 yr-1), and gradually decreases thereafter. The dynamic patterns of C sinks in vegetation and soil are significantly different. C sink in vegetation first increases rapidly with age and then decreases. C sink in soil, however, increases continuously with age; it acts as a C source when the age is less than 20 years, after which it acts as a sink. For the evergreen needle-leaved forest, the highest C sink efficiency (i.e., C sink per unit net primary productivity) is approximately 60%, with age between 11 and 43 years. Overall, the inverse estimation of carbon cycle parameters can make reasonable estimates of age-dependent C sequestration in forests.

  2. A SIRS epidemic model with infection-age dependence

    NASA Astrophysics Data System (ADS)

    Zhang, Zhonghua; Peng, Jigen

    2007-07-01

    Based on J. Mena-Lorca and H.W. Hethcote's epidemic model, a SIRS epidemic model with infection-age-dependent infectivity and general nonlinear contact rate is formulated. Under general conditions, the unique existence of its global positive solutions is obtained. Moreover, under more general assumptions than the existing, the existence and asymptotical stability of its equilibria are discussed. In the end, the condition on the stability of endemic equilibrium is verified by a special model.

  3. Why is the dog an ideal model for aging research?

    PubMed

    Gilmore, Keiva M; Greer, Kimberly A

    2015-11-01

    With many caveats to the traditional vertebrate species pertaining to biogerontology investigations, it has been suggested that a most informative model is the one which: 1) examines closely related species, or various members of the same species with naturally occurring lifespan variation, 2) already has adequate medical procedures developed, 3) has a well annotated genome, 4) does not require artificial housing, and can live in its natural environment while being investigated, and 5) allows considerable information to be gathered within a relatively short period of time. The domestic dog unsurprisingly fits each criterion mentioned. The dog has already become a key model system in which to evaluate surgical techniques and novel medications because of the remarkable similarity between human and canine conditions, treatments, and response to therapy. The dog naturally serves as a disease model for study, obviating the need to construct artificial genetically modified examples of disease. Just as the dog offers a natural model for human conditions and diseases, simple observation leads to the conclusion that the canine aging phenotype also mimics that of the human. Genotype information, biochemical information pertaining to the GH/IGF-1 pathway, and some limited longitudinal investigations have begun the establishment of the domestic dog as a model of aging. Although we find that dogs indeed are a model to study aging and there are many independent pieces of canine aging data, there are many more "open" areas, ripe for investigation. PMID:26325590

  4. Impact of aging mechanism on model simulated carbonaceous aerosols

    NASA Astrophysics Data System (ADS)

    Huang, Y.; Wu, S.; Dubey, M. K.; French, N. H. F.

    2013-07-01

    Carbonaceous aerosols including organic carbon and black carbon have significant implications for both climate and air quality. In the current global climate or chemical transport models, a fixed hydrophobic-to-hydrophilic conversion lifetime for carbonaceous aerosol (τ) is generally assumed, which is usually around one day. We have implemented a new detailed aging scheme for carbonaceous aerosols in a chemical transport model (GEOS-Chem) to account for both the chemical oxidation and the physical condensation-coagulation effects, where τ is affected by local atmospheric environment including atmospheric concentrations of water vapor, ozone, hydroxyl radical and sulfuric acid. The updated τ exhibits large spatial and temporal variations with the global average (up to 11 km altitude) calculated to be 2.6 days. The chemical aging effects are found to be strongest over the tropical regions driven by the low ozone concentrations and high humidity there. The τ resulted from chemical aging generally decreases with altitude due to increases in ozone concentration and decreases in humidity. The condensation-coagulation effects are found to be most important for the high-latitude areas, in particular the polar regions, where the τ values are calculated to be up to 15 days. When both the chemical aging and condensation-coagulation effects are considered, the total atmospheric burdens and global average lifetimes of BC, black carbon, (OC, organic carbon) are calculated to increase by 9% (3%) compared to the control simulation, with considerable enhancements of BC and OC concentrations in the Southern Hemisphere. Model evaluations against data from multiple datasets show that the updated aging scheme improves model simulations of carbonaceous aerosols for some regions, especially for the remote areas in the Northern Hemisphere. The improvement helps explain the persistent low model bias for carbonaceous aerosols in the Northern Hemisphere reported in literature. Further

  5. Cellular senescence in the Penna model of aging

    NASA Astrophysics Data System (ADS)

    Periwal, Avikar

    2013-11-01

    Cellular senescence is thought to play a major role in age-related diseases, which cause nearly 67% of all human deaths worldwide. Recent research in mice showed that exercising mice had higher levels of telomerase, an enzyme that helps maintain telomere length, than nonexercising mice. A commonly used model for biological aging was proposed by Penna. I propose a modification of the Penna model that incorporates cellular senescence and find an analytical steady-state solution following Coe, Mao, and Cates [Phys. Rev. Lett.PRLTAO0031-900710.1103/PhysRevLett.89.288103 89, 288103 (2002)]. I find that models corresponding to delayed cellular senescence have younger populations that live longer. I fit the model to the United Kingdom's death distribution, which the original Penna model cannot do.

  6. Computationally Modeling Lipid Metabolism and Aging: A Mini-review.

    PubMed

    Mc Auley, Mark T; Mooney, Kathleen M

    2015-01-01

    One of the greatest challenges in biology is to improve the understanding of the mechanisms which underpin aging and how these affect health. The need to better understand aging is amplified by demographic changes, which have caused a gradual increase in the global population of older people. Aging western populations have resulted in a rise in the prevalence of age-related pathologies. Of these diseases, cardiovascular disease is the most common underlying condition in older people. The dysregulation of lipid metabolism due to aging impinges significantly on cardiovascular health. However, the multifaceted nature of lipid metabolism and the complexities of its interaction with aging make it challenging to understand by conventional means. To address this challenge computational modeling, a key component of the systems biology paradigm is being used to study the dynamics of lipid metabolism. This mini-review briefly outlines the key regulators of lipid metabolism, their dysregulation, and how computational modeling is being used to gain an increased insight into this system. PMID:25750699

  7. Computationally Modeling Lipid Metabolism and Aging: A Mini-review

    PubMed Central

    Mc Auley, Mark T.; Mooney, Kathleen M.

    2014-01-01

    One of the greatest challenges in biology is to improve the understanding of the mechanisms which underpin aging and how these affect health. The need to better understand aging is amplified by demographic changes, which have caused a gradual increase in the global population of older people. Aging western populations have resulted in a rise in the prevalence of age-related pathologies. Of these diseases, cardiovascular disease is the most common underlying condition in older people. The dysregulation of lipid metabolism due to aging impinges significantly on cardiovascular health. However, the multifaceted nature of lipid metabolism and the complexities of its interaction with aging make it challenging to understand by conventional means. To address this challenge computational modeling, a key component of the systems biology paradigm is being used to study the dynamics of lipid metabolism. This mini-review briefly outlines the key regulators of lipid metabolism, their dysregulation, and how computational modeling is being used to gain an increased insight into this system. PMID:25750699

  8. An evaluation of sex-age-kill (SAK) model performance

    USGS Publications Warehouse

    Millspaugh, Joshua J.; Skalski, John R.; Townsend, Richard L.; Diefenbach, Duane R.; Boyce, Mark S.; Hansen, Lonnie P.; Kammermeyer, Kent

    2009-01-01

    The sex-age-kill (SAK) model is widely used to estimate abundance of harvested large mammals, including white-tailed deer (Odocoileus virginianus). Despite a long history of use, few formal evaluations of SAK performance exist. We investigated how violations of the stable age distribution and stationary population assumption, changes to male or female harvest, stochastic effects (i.e., random fluctuations in recruitment and survival), and sampling efforts influenced SAK estimation. When the simulated population had a stable age distribution and λ > 1, the SAK model underestimated abundance. Conversely, when λ < 1, the SAK overestimated abundance. When changes to male harvest were introduced, SAK estimates were opposite the true population trend. In contrast, SAK estimates were robust to changes in female harvest rates. Stochastic effects caused SAK estimates to fluctuate about their equilibrium abundance, but the effect dampened as the size of the surveyed population increased. When we considered both stochastic effects and sampling error at a deer management unit scale the resultant abundance estimates were within ±121.9% of the true population level 95% of the time. These combined results demonstrate extreme sensitivity to model violations and scale of analysis. Without changes to model formulation, the SAK model will be biased when λ ≠ 1. Furthermore, any factor that alters the male harvest rate, such as changes to regulations or changes in hunter attitudes, will bias population estimates. Sex-age-kill estimates may be precise at large spatial scales, such as the state level, but less so at the individual management unit level. Alternative models, such as statistical age-at-harvest models, which require similar data types, might allow for more robust, broad-scale demographic assessments.

  9. Development of a bioenergetics model for age-0 American Shad

    USGS Publications Warehouse

    Sauter, Sally T.

    2011-01-01

    Bioenergetics modeling can be used as a tool to investigate the impact of non-native age-0 American shad (Alosa sapidissima) on reservoir and estuary food webs. The model can increase our understanding of how these fish influence lower trophic levels as well as predatory fish populations that feed on juvenile salmonids. Bioenergetics modeling can be used to investigate ecological processes, evaluate alternative research hypotheses, provide decision support, and quantitative prediction. Bioenergetics modeling has proven to be extremely useful in fisheries research (Ney et al. 1993,Chips and Wahl 2008, Petersen et al. 2008). If growth and diet parameters are known, the bioenergetics model can be used to quantify the relative amount of zooplankton or insects consumed by age-0 American shad. When linked with spatial and temporal information on fish abundance, model output can guide inferential hypothesis development to demonstrate where the greatest impacts of age-0 American shad might occur.


    Bioenergetics modeling is particularly useful when research questions involve multiple species and trophic levels (e.g. plankton communities). Bioenergetics models are mass-balance equations where the energy acquired from food is partitioned between maintenance costs, waste products, and growth (Winberg 1956). Specifically, the Wisconsin bioenergetics model (Hanson et al. 1997) is widely used in fisheries science. Researchers have extensively tested, reviewed, and improved on this modeling approach for over 30 years (Petersen et al. 2008). Development of a bioenergetics model for any species requires three key components: 1) determine physiological parameters for the model through laboratory experiments or incorporate data from a closely related species, 2) corroboration of the model with growth and consumption estimates from independent research, and 3) error analysis of model parameters.


    Wisconsin bioenergetics models have been parameterized for

  10. Recent female mouse models displaying advanced reproductive aging.

    PubMed

    Danilovich, Natalia; Ram Sairam, M

    2006-02-01

    Reproductive senescence occurs in all female mammals with resultant changes in numerous body functional systems and several important features may be species-specific. Those features that appear to parallel human menopause and aging include general similarity of hormone profiles across the menopausal transition, progression to cycle termination through irregular cycles, declining fertility with age, disturbances in thermogenesis, age-related gains in body weight, fat distribution and disposition towards metabolic syndrome. Structural and hormonal changes in the brain and ovary play a critical role in determining the onset of reproductive senescence. The short life span of rodents such as mice (compared to humans) and the ability to generate specific and timed gene deletions, provide powerful experimental paradigms to understand the molecular and functional changes that precede and follow the loss of reproductive capacity. In theory, any manipulation that compromises ovarian function either partly or totally would impact reproductive events at various levels followed by other dysfunctions. In this article, we provide an overview of three mouse models for the study of female reproductive aging. They are derived from different strategies and their age related phenotypes have been characterized to varying degrees. The follitropin receptor knockout (FORKO) mouse, in its null and haploinsufficient state as well as the dioxin/aryl hydrocarbon receptor (AhR) knockout mouse, serve as two examples of single gene deletions. A third model, using administration of a chemical toxicant such as 4-vinylcyclohexene diepoxide (VCD) in the adult state, produces ovarian deficiencies accompanied by aging changes. These will serve as useful alternatives to previously used radical ovariectomy in young adults. It is anticipated that these new models and more that will be forthcoming will extend opportunities to understand reproductive aging and resolve controversies that abound on issues

  11. Testing a model of aging in animal experiments.

    PubMed

    Tyurin YuN; Yakovlev AYu; Shi, J; Bass, L

    1995-03-01

    A stochastic model of aging is developed in terms of accumulation and expression of intracellular lesions caused by environment or intrinsic genetic program. In contrast to the commonly used Gompertz-Makeham approach to the parametric analysis of mortality data, the model yields a hazard function that is bounded from above. For testing the model in experiments aimed at studying animal longevity, a Kolmogorov-type statistical test is presented with regard to the hypothesis involving unknown parameters. Examples concerning longevity of intact animals of two different species, as well as the effect of a prolonged irradiation at a low dose rate, are given to illustrate the model application and goodness-of-fit testing. The results of the analysis of published data show that the rate of lesion formation is not sustained at a constant level throughout life, though in some cases its variations with age can be considered negligible. PMID:7766791

  12. Reconciling Two Computational Models of Working Memory in Aging.

    PubMed

    Hoareau, Violette; Lemaire, Benoît; Portrat, Sophie; Plancher, Gaën

    2016-01-01

    It is well known that working memory performance changes with age. Two recent computational models of working memory, TBRS* and SOB-CS, developed from young adults WM performances are opposed regarding the postulated causes of forgetting, namely time-based decay and interference for TBRS* and SOB-CS, respectively. In the present study, these models are applied on a set of complex span data produced by young and older adults. As expected, these models are unable to account for the older adult data. An investigation on the effect of the main parameters of these models showed that the poorer performance of older adults does not come from a weaker encoding of item but rather from difficulties during the free time that immediately follows each distractor, as well as from a higher level of confusion between items. These results are discussed with respect to the current theories of working memory and aging. PMID:26748955

  13. Advertising, Consensus, and Aging in Multilayer Sznajd Model

    NASA Astrophysics Data System (ADS)

    Schulze, Christian

    In the Sznajd consensus model on the square lattice, two people who agree in their opinions convince their neighbors of this opinion. We generalize it to many layers representing many age levels, and check if a consensus among all layers is possible. Advertising sometimes, but not always, produces a consensus on the advertised opinion.

  14. Modeling sugarcane growth in response to age, insolation, and temperature

    SciTech Connect

    How, K.T.S.

    1986-01-01

    Modeling sugarcane growth in response to age of cane, insolation and air temperature using first-order multiple regression analysis and a nonlinear approach is investigated. Data are restricted to one variety from irrigated fields to eliminate the impact of varietal response and rainfall. Ten first-order models are investigated. The predictant is cane yield from 600 field tests. The predictors are cumulative values of insolation, maximum temperature, and minimum temperature for 3, 6, 12, and 18 months, or for each crop period derived from weather observations near the test plots. The low R-square values indicate that the selected predictor variables could not account for a substantial proportion of the variations of cane yield and the models have limited predictive values. The nonlinear model is based on known functional relationships between growth and age, growth and insolation, and growth and maximum temperature. A mathematical expression that integrates the effect of age, insolation and maximum temperature is developed. The constant terms and coefficients of the equation are determined from the requirement that the model must produce results that are reasonable when compared with observed monthly elongation data. The nonlinear model is validated and tested using another set of data.

  15. Regulation of Aerobic Energy Metabolism in Podospora anserina by Two Paralogous Genes Encoding Structurally Different c-Subunits of ATP Synthase

    PubMed Central

    Sellem, Carole H.; di Rago, Jean-Paul; Lasserre, Jean-Paul; Ackerman, Sharon H.; Sainsard-Chanet, Annie

    2016-01-01

    Most of the ATP in living cells is produced by an F-type ATP synthase. This enzyme uses the energy of a transmembrane electrochemical proton gradient to synthesize ATP from ADP and inorganic phosphate. Proton movements across the membrane domain (FO) of the ATP synthase drive the rotation of a ring of 8–15 c-subunits, which induces conformational changes in the catalytic part (F1) of the enzyme that ultimately promote ATP synthesis. Two paralogous nuclear genes, called Atp9-5 and Atp9-7, encode structurally different c-subunits in the filamentous fungus Podospora anserina. We have in this study identified differences in the expression pattern for the two genes that correlate with the mitotic activity of cells in vegetative mycelia: Atp9-7 is transcriptionally active in non-proliferating (stationary) cells while Atp9-5 is expressed in the cells at the extremity (apex) of filaments that divide and are responsible for mycelium growth. When active, the Atp9-5 gene sustains a much higher rate of c-subunit synthesis than Atp9-7. We further show that the ATP9-7 and ATP9-5 proteins have antagonist effects on the longevity of P. anserina. Finally, we provide evidence that the ATP9-5 protein sustains a higher rate of mitochondrial ATP synthesis and yield in ATP molecules per electron transferred to oxygen than the c-subunit encoded by Atp9-7. These findings reveal that the c-subunit genes play a key role in the modulation of ATP synthase production and activity along the life cycle of P. anserina. Such a degree of sophistication for regulating aerobic energy metabolism has not been described before. PMID:27442014

  16. Muscle wasting and aging: Experimental models, fatty infiltrations, and prevention.

    PubMed

    Brioche, Thomas; Pagano, Allan F; Py, Guillaume; Chopard, Angèle

    2016-08-01

    Identification of cost-effective interventions to maintain muscle mass, muscle strength, and physical performance during muscle wasting and aging is an important public health challenge. It requires understanding of the cellular and molecular mechanisms involved. Muscle-deconditioning processes have been deciphered by means of several experimental models, bringing together the opportunities to devise comprehensive analysis of muscle wasting. Studies have increasingly recognized the importance of fatty infiltrations or intermuscular adipose tissue for the age-mediated loss of skeletal-muscle function and emphasized that this new important factor is closely linked to inactivity. The present review aims to address three main points. We first mainly focus on available experimental models involving cell, animal, or human experiments on muscle wasting. We next point out the role of intermuscular adipose tissue in muscle wasting and aging and try to highlight new findings concerning aging and muscle-resident mesenchymal stem cells called fibro/adipogenic progenitors by linking some cellular players implicated in both FAP fate modulation and advancing age. In the last part, we review the main data on the efficiency and molecular and cellular mechanisms by which exercise, replacement hormone therapies, and β-hydroxy-β-methylbutyrate prevent muscle wasting and sarcopenia. Finally, we will discuss a potential therapeutic target of sarcopenia: glucose 6-phosphate dehydrogenase. PMID:27106402

  17. Mindspan: Lessons from Rat Models of Neurocognitive Aging

    PubMed Central

    Gallagher, Michela; Stocker, Amy; Koh, Ming Teng

    2011-01-01

    Research on the biology of aging seeks to enhance understanding of basic mechanisms and thus support improvements in outcomes throughout the lifespan, including longevity itself, susceptibility to disease, and life-long adaptive capacities. The focus of this review is the use of rats as an animal model of cognitive change during aging, and specifically lessons learned from aging rats in behavioral studies of cognitive processes mediated by specialized neural circuitry. An advantage of this approach is the ability to compare brain aging across species where functional homology exists for specific neural systems; in this article we focus on behavioral assessments that target the functions of the medial temporal lobe and prefrontal cortex. We also take a critical look at studies using calorie restriction (CR) as a well-defined experimental approach to manipulating biological aging. We conclude that the effects of CR on cognitive aging in rats are less well established than commonly assumed, with much less supportive evidence relative to its benefits on longevity and susceptibility to disease, and that more research in this area is necessary. PMID:21411856

  18. Technical Note: Probabilistically constraining proxy age-depth models within a Bayesian hierarchical reconstruction model

    NASA Astrophysics Data System (ADS)

    Werner, J. P.; Tingley, M. P.

    2014-12-01

    Reconstructions of late-Holocene climate rely heavily upon proxies that are assumed to be accurately dated by layer counting, such as measurement on tree rings, ice cores, and varved lake sediments. Considerable advances may be achievable if time uncertain proxies could be included within these multiproxy reconstructions, and if time uncertainties were recognized and correctly modeled for proxies commonly treated as free of age model errors. Current approaches to accounting for time uncertainty are generally limited to repeating the reconstruction using each of an ensemble of age models, thereby inflating the final estimated uncertainty - in effect, each possible age model is given equal weighting. Uncertainties can be reduced by exploiting the inferred space-time covariance structure of the climate to re-weight the possible age models. Here we demonstrate how Bayesian Hierarchical climate reconstruction models can be augmented to account for time uncertain proxies. Critically, while a priori all age models are given equal probability of being correct, the probabilities associated with the age models are formally updated within the Bayesian framework, thereby reducing uncertainties. Numerical experiments show that updating the age-model probabilities decreases uncertainty in the climate reconstruction, as compared with the current de-facto standard of sampling over all age models, provided there is sufficient information from other data sources in the region of the time-uncertain proxy. This approach can readily be generalized to non-layer counted proxies, such as those derived from marine sediments.

  19. Technical Note: Probabilistically constraining proxy age-depth models within a Bayesian hierarchical reconstruction model

    NASA Astrophysics Data System (ADS)

    Werner, J. P.; Tingley, M. P.

    2015-03-01

    Reconstructions of the late-Holocene climate rely heavily upon proxies that are assumed to be accurately dated by layer counting, such as measurements of tree rings, ice cores, and varved lake sediments. Considerable advances could be achieved if time-uncertain proxies were able to be included within these multiproxy reconstructions, and if time uncertainties were recognized and correctly modeled for proxies commonly treated as free of age model errors. Current approaches for accounting for time uncertainty are generally limited to repeating the reconstruction using each one of an ensemble of age models, thereby inflating the final estimated uncertainty - in effect, each possible age model is given equal weighting. Uncertainties can be reduced by exploiting the inferred space-time covariance structure of the climate to re-weight the possible age models. Here, we demonstrate how Bayesian hierarchical climate reconstruction models can be augmented to account for time-uncertain proxies. Critically, although a priori all age models are given equal probability of being correct, the probabilities associated with the age models are formally updated within the Bayesian framework, thereby reducing uncertainties. Numerical experiments show that updating the age model probabilities decreases uncertainty in the resulting reconstructions, as compared with the current de facto standard of sampling over all age models, provided there is sufficient information from other data sources in the spatial region of the time-uncertain proxy. This approach can readily be generalized to non-layer-counted proxies, such as those derived from marine sediments.

  20. Probabilistically constraining proxy age-depth models within a Bayesian hierarchical reconstruction model

    NASA Astrophysics Data System (ADS)

    Werner, Johannes; Tingley, Martin

    2015-04-01

    Reconstructions of late-Holocene climate rely heavily upon proxies that are assumed to be accurately dated by layer counting, such as measurement on tree rings, ice cores, and varved lake sediments. Considerable advances may be achievable if time uncertain proxies could be included within these multiproxy reconstructions, and if time uncertainties were recognized and correctly modeled for proxies commonly treated as free of age model errors. Current approaches to accounting for time uncertainty are generally limited to repeating the reconstruction using each of an ensemble of age models, thereby inflating the final estimated uncertainty - in effect, each possible age model is given equal weighting. Uncertainties can be reduced by exploiting the inferred space-time covariance structure of the climate to re-weight the possible age models. Here we demonstrate how Bayesian Hierarchical climate reconstruction models can be augmented to account for time uncertain proxies. Critically, while a priori all age models are given equal probability of being correct, the probabilities associated with the age models are formally updated within the Bayesian framework, thereby reducing uncertainties. Numerical experiments show that updating the age model probabilities decreases uncertainty in the climate reconstruction, as compared with the current de-facto standard of sampling over all age models, provided there is sufficient information from other data sources in the region of the time-uncertain proxy. This approach can readily be generalized to non-layer counted proxies, such as those derived from marine sediments. Werner and Tingley, Climate of the Past Discussions (2014)

  1. Rotifers as models for the biology of aging

    PubMed Central

    Snell, Terry W.

    2013-01-01

    It has been two decades since 1993 when research on the biology of rotifer aging was last reviewed by Enesco. Much has transpired during this time as rotifer biologists have adapted to the “omics” revolution and incorporated these techniques into the experimental analysis of rotifers. Rotifers are amenable to many of these approaches and getting adequate quantities of DNA, RNA, and protein from rotifers is not difficult. Analysis of rotifer genomes, transcriptomes, and proteomes is rapidly yielding candidate genes that likely regulate a variety of features of rotifer biology. Parallel developments in aging biology have recognized the limitations of standard animal models like worms and flies and that comparative aging research has essentially ignored a large fraction of animal phylogeny in the lophotrochozoans. As experimentally tractable members of this group, rotifers have attracted interest as models of aging. In this paper, I review advances over the past 20 years in the biology of aging in rotifers, with emphasis on the unique contributions of rotifer models for understanding aging. The majority of experimental work has manipulated rotifer diet and followed changes in survival and reproductive dynamics like mean lifespan, maximum lifespan, reproductive lifespan, and mortality rate doubling time. The main dietary manipulation has been some form of caloric restriction, withholding food for some period or feeding continuously at low levels. There have been comparative studies of several rotifer species, with some species responding to caloric restriction with life extension, but others not, at least under the tested food regimens. Other aspects of diet are less explored, like nutritional properties of different algae species and their capacity to extend rotifer lifespan. Several descriptive studies have reported many genes involved in rotifer aging by comparing gene expression in young and old individuals. Classes of genes up or down-regulated during aging

  2. Anomalous scaling in an age-dependent branching model

    NASA Astrophysics Data System (ADS)

    Keller-Schmidt, Stephanie; Tuǧrul, Murat; Eguíluz, Víctor M.; Hernández-García, Emilio; Klemm, Konstantin

    2015-02-01

    We introduce a one-parametric family of tree growth models, in which branching probabilities decrease with branch age τ as τ-α. Depending on the exponent α , the scaling of tree depth with tree size n displays a transition between the logarithmic scaling of random trees and an algebraic growth. At the transition (α =1 ) tree depth grows as (logn) 2. This anomalous scaling is in good agreement with the trend observed in evolution of biological species, thus providing a theoretical support for age-dependent speciation and associating it to the occurrence of a critical point.

  3. Modelling safety of multistate systems with ageing components

    NASA Astrophysics Data System (ADS)

    Kołowrocki, Krzysztof; Soszyńska-Budny, Joanna

    2016-06-01

    An innovative approach to safety analysis of multistate ageing systems is presented. Basic notions of the ageing multistate systems safety analysis are introduced. The system components and the system multistate safety functions are defined. The mean values and variances of the multistate systems lifetimes in the safety state subsets and the mean values of their lifetimes in the particular safety states are defined. The multi-state system risk function and the moment of exceeding by the system the critical safety state are introduced. Applications of the proposed multistate system safety models to the evaluation and prediction of the safty characteristics of the consecutive "m out of n: F" is presented as well.

  4. Scaling in a Continuous Time Model for Biological Aging

    NASA Astrophysics Data System (ADS)

    de Almeida, R. M. C.; Thomas, G. L.

    In this paper, we consider a generalization to the asexual version of Penna model for biological aging, where we take a continuous time limit. The genotype associated to each individual is an interval of real numbers over which Dirac δ-functions are defined, representing genetically programmed diseases to be switched on at defined ages of the individual life. We discuss two different continuous limits for the evolution equation and two different mutation protocols, to be implemented during reproduction. Exact stationary solutions are obtained and scaling properties are discussed.

  5. Anomalous scaling in an age-dependent branching model.

    PubMed

    Keller-Schmidt, Stephanie; Tuğrul, Murat; Eguíluz, Víctor M; Hernández-García, Emilio; Klemm, Konstantin

    2015-02-01

    We introduce a one-parametric family of tree growth models, in which branching probabilities decrease with branch age τ as τ(-α). Depending on the exponent α, the scaling of tree depth with tree size n displays a transition between the logarithmic scaling of random trees and an algebraic growth. At the transition (α=1) tree depth grows as (logn)(2). This anomalous scaling is in good agreement with the trend observed in evolution of biological species, thus providing a theoretical support for age-dependent speciation and associating it to the occurrence of a critical point. PMID:25768548

  6. Computer simulation of Aphis gossypii insects using Penna aging model

    NASA Astrophysics Data System (ADS)

    Giarola, L. T. P.; Martins, S. G. F.; Toledo Costa, M. C. P.

    2006-08-01

    A computer simulation was made for the population dynamics of Aphis gossypii in laboratory and field conditions. The age structure was inserted in the dynamics through bit string model for biological aging, proposed by Penna in 1995. The influence of different host plants and of climatic factors such as temperature and precipitation was considered in the simulation starting from experimental data. The results obtained indicate that the simulation is an appropriate instrument for understanding of the population dynamics of these species and for the establishment of biological control strategies.

  7. Aging, Neurogenesis, and Caloric Restriction in Different Model Organisms

    PubMed Central

    Arslan-Ergul, Ayca; Ozdemir, A Tugrul; Adams, Michelle M

    2013-01-01

    Brain aging is a multifactorial process that is occurring across multiple cognitive domains. A significant complaint that occurs in the elderly is a decrement in learning and memory ability. Both rodents and zebrafish exhibit a similar problem with memory during aging. The neurobiological changes that underlie this cognitive decline are complex and undoubtedly influenced by many factors. Alterations in the birth of new neurons and neuron turnover may contribute to age-related cognitive problems. Caloric restriction is the only non-genetic intervention that reliably increases life span and healthspan across multiple organisms although the molecular mechanisms are not well-understood. Recently the zebrafish has become a popular model organism for understanding the neurobiological consequences but to date very little work has been performed. Similarly, few studies have examined the effects of dietary restriction in zebrafish. Here we review the literature related to memory decline, neurogenesis, and caloric restriction across model organisms and suggest that zebrafish has the potential to be an important animal model for understanding the complex interactions between age, neurobiological changes in the brain, and dietary regimens or their mimetics as interventions. PMID:23936746

  8. Impact of aging mechanism on model simulated carbonaceous aerosols

    PubMed Central

    Huang, Y.; Wu, S.; Dubey, M.K.; French, N. H. F.

    2013-01-01

    Carbonaceous aerosols including organic carbon and black carbon have significant implications for both climate and air quality. In the current global climate or chemical transport models, a fixed hydrophobic-to-hydrophilic conversion lifetime for carbonaceous aerosol (τ) is generally assumed, which is usually around one day. We have implemented a new detailed aging scheme for carbonaceous aerosols in a chemical transport model (GEOS-Chem) to account for both the chemical oxidation and the physical condensation-coagulation effects, where τ is affected by local atmospheric environment including atmospheric concentrations of water vapor, ozone, hydroxyl radical and sulfuric acid. The updated τ exhibits large spatial and temporal variations with the global average (up to 11 km altitude) calculated to be 2.6 days. The chemical aging effects are found to be strongest over the tropical regions driven by the low ozone concentrations and high humidity there. The τ resulted from chemical aging generally decreases with altitude due to increases in ozone concentration and decreases in humidity. The condensation-coagulation effects are found to be most important for the high-latitude areas, in particular the polar regions, where the τ values are calculated to be up to 15 days. When both the chemical aging and condensation-coagulation effects are considered, the total atmospheric burdens and global average lifetimes of BC, black carbon, (OC, organic carbon) are calculated to increase by 9% (3%) compared to the control simulation, with considerable enhancements of BC and OC concentrations in the Southern Hemisphere. Model evaluations against data from multiple datasets show that the updated aging scheme improves model simulations of carbonaceous aerosols for some regions, especially for the remote areas in the Northern Hemisphere. The improvement helps explain the persistent low model bias for carbonaceous aerosols in the Northern Hemisphere reported in literature. Further

  9. Geophysical Age Dating of Seamounts using Dense Core Flexure Model

    NASA Astrophysics Data System (ADS)

    Hwang, Gyuha; Kim, Seung-Sep

    2016-04-01

    Lithospheric flexure of oceanic plate is thermo-mechanical response of an elastic plate to the given volcanic construct (e.g., seamounts and ocean islands). If the shape and mass of such volcanic loads are known, the flexural response is governed by the thickness of elastic plate, Te. As the age of oceanic plate increases, the elastic thickness of oceanic lithosphere becomes thicker. Thus, we can relate Te with the age of plate at the time of loading. To estimate the amount of the driving force due to seamounts on elastic plate, one needs to approximate their density structure. The most common choice is uniform density model, which utilizes constant density value for a seamount. This approach simplifies computational processes for gravity prediction and error estimates. However, the uniform density model tends to overestimate the total mass of the seamount and hence produces more positive gravitational contributions from the load. Minimization of gravity misfits using uniform density, therefore, favors thinner Te in order to increase negative contributions from the lithospheric flexure, which can compensate for the excessive positives from the seamount. An alternative approach is dense core model, which approximate the heterogeneity nature of seamount density as three bodies of infill sediment, edifice, and dense core. In this study, we apply the dense core model to the Louisville Seamount Chain for constraining flexural deformation. We compare Te estimates with the loading time of the examined seamounts to redefine empirical geophysical age dating of seamounts.

  10. Mechanical Regulation of Cardiac Aging in Model Systems.

    PubMed

    Sessions, Ayla O; Engler, Adam J

    2016-05-13

    Unlike diet and exercise, which individuals can modulate according to their lifestyle, aging is unavoidable. With normal or healthy aging, the heart undergoes extensive vascular, cellular, and interstitial molecular changes that result in stiffer less compliant hearts that experience a general decline in organ function. Although these molecular changes deemed cardiac remodeling were once thought to be concomitant with advanced cardiovascular disease, they can be found in patients without manifestation of clinical disease. It is now mostly acknowledged that these age-related mechanical changes confer vulnerability of the heart to cardiovascular stresses associated with disease, such as hypertension and atherosclerosis. However, recent studies have aimed at differentiating the initial compensatory changes that occur within the heart with age to maintain contractile function from the maladaptive responses associated with disease. This work has identified new targets to improve cardiac function during aging. Spanning invertebrate to vertebrate models, we use this review to delineate some hallmarks of physiological versus pathological remodeling that occur in the cardiomyocyte and its microenvironment, focusing especially on the mechanical changes that occur within the sarcomere, intercalated disc, costamere, and extracellular matrix. PMID:27174949

  11. Spectral age modelling of the `Sausage' cluster radio relic

    NASA Astrophysics Data System (ADS)

    Stroe, Andra; Harwood, Jeremy J.; Hardcastle, Martin J.; Röttgering, Huub J. A.

    2014-12-01

    CIZA J2242.8+5301 is a post-core passage, binary merging cluster that hosts a large, thin, arc-like radio relic, nicknamed the `Sausage', tracing a relatively strong shock front. We perform spatially resolved spectral fitting to the available radio data for this radio relic, using a variety of spectral ageing models, with the aim of finding a consistent set of parameters for the shock and radio plasma. We determine an injection index of 0.77^{+0.03}_{-0.02} for the relic plasma, significantly steeper than was found before. Standard particle acceleration at the shock front implies a Mach number M=2.90^{+0.10}_{-0.13}, which now matches X-ray measurements. The shock advance speed is vshock ≈ 2500 km s-1, which places the core passage of the two subclusters 0.6-0.8 Gyr ago. We find a systematic spectral age increase from 0 at the northern side of the relic up to ˜60 Myr at ˜145 kpc into the downstream area, assuming a 0.6 nT magnetic field. Under the assumption of freely ageing electrons after acceleration by the `Sausage' shock, the spectral ages are hard to reconcile with the shock speed derived from X-ray and radio observations. Re-acceleration or unusually efficient transport of particle in the downstream area and line-of-sight mixing could help explain the systematically low spectral ages.

  12. Predicting mortality from burns: the need for age-group specific models.

    PubMed

    Taylor, Sandra L; Lawless, MaryBeth; Curri, Terese; Sen, Soman; Greenhalgh, David G; Palmieri, Tina L

    2014-09-01

    Traditional burn mortality models are derived using all age groups. We hypothesized that age variably impacts mortality after burn and that age-specific models for children, adults, and seniors will more accurately predict mortality than an all-ages model. We audited data from the American Burn Association (ABA) National Burn Repository (NBR) from 2000 to 2009 and used mixed effect logistic regression models to assess the influence of age, total body surface area (TBSA) burn, and inhalation injury on mortality. Mortality models were constructed for all ages and age-specific models: children (<18 years), adults (18-60 years), and seniors (>60 years). Model performance was assessed by area under the receiver operating curve (AUC). Main effect and two-way interactions were used to construct age-group specific mortality models. Each age-specific model was compared to the All Ages model. Of 286,293 records 100,051 had complete data. Overall mortality was 4% but varied by age (17% seniors, <1% children). Age, TBSA, and inhalation injury were significant mortality predictors for all models (p<0.05). Differences in predicted mortality between the All Ages model and the age-specific models occurred in children and seniors. In the age-specific pediatric model, predicted mortality decreased with age; inhalation injury had greater effect on mortality than in the All Ages model. In the senior model mortality increased with age. Seniors had greater increase in mortality per 1% increment in burn size and 1 year increase in age than other ages. The predicted mortality in seniors using the senior-specific model was higher than in the All Ages model. "One size fits all" models for predicting burn outcomes do not accurately reflect the outcomes for seniors and children. Age-specific models for children and seniors may be advisable. PMID:24846014

  13. Zebrafish (Danio rerio) as a model for the study of aging and exercise: physical ability and trainability decrease with age.

    PubMed

    Gilbert, Matthew J H; Zerulla, Tanja C; Tierney, Keith B

    2014-02-01

    A rapidly aging global population has motivated the development and use of models for human aging. Studies on aging have shown parallels between zebrafish and humans at the internal organization level; however, few parallels have been studied at the whole-organism level. Furthermore, the effectiveness of exercise as a method to mitigate the effects of aging has not been studied in zebrafish. We investigated the effects of aging and intermittent exercise on swimming performance, kinematics and behavior. Young, middle-aged and old zebrafish (20-29, 36-48 and 60-71% of average lifespan, respectively) were exercised to exhaustion in endurance and sprint swimming tests once a week for four weeks. Both endurance and sprint performance decreased with increased age. Swimming performance improved with exercise training in young and middle-aged zebrafish, but not in old zebrafish. Tail-beat amplitude, which is akin to stride length in humans, increased for all age groups with training. Zebrafish turning frequency, which is an indicator of routine activity, decreased with age but showed no change with exercise. In sum, our results show that zebrafish exhibit a decline in whole-organism performance and trainability with age. These findings closely resemble the senescence-related declines in physical ability experienced by humans and mammalian aging models and therefore support the use of zebrafish as a model for human exercise and aging. PMID:24316042

  14. Modeling Aging and Mechanical Rejuvenation of Amorphous Solids

    NASA Astrophysics Data System (ADS)

    Semkiv, Mykhailo; Hütter, Markus

    2016-04-01

    The elasto-viscoplasticity of amorphous solids is modeled, with a focus on the effects of physical aging and mechanical rejuvenation. Using nonequilibrium thermodynamics, the concept of kinetic and configurational subsystems has been employed. The Hamiltonian structure of reversible dynamics is exploited to derive a constitutive relation for the stress tensor. Furthermore, it is demonstrated that accounting for mechanical rejuvenation results in a modification of the driving force for viscoplastic flow.

  15. Ageing of polymer bonds: a coupled chemomechanical modelling approach

    NASA Astrophysics Data System (ADS)

    Dippel, Benedikt; Johlitz, Michael; Lion, Alexander

    2014-05-01

    With the increasing number of requirements on joinings, it gets more and more important to understand and predict an assemblies properties. Nowadays, in industrial applications, combinations of different materials get more common. In most of those cases, it is, besides other advantages, useful to connect such parts with adhesives to avoid local cells. Thus, the knowledge about the mechanical behaviour of adhesives over the whole time of utilisation is an essential element of engineering. As it is well known, ageing due to environmental influences such as oxygen, radiation, ozone and others plays a major role in polymers properties. So, for the prediction of applicability over the whole lifetime of a technical component, the change in mechanical properties due to ageing is necessary. In this contribution, we introduce a material model which takes into account the internal structure of an adhesive. Therefore, an interphase zone is introduced. In the interphase, which is developed due to the contact of an adhesive with an adherent, the materials properties change continuously from the surface to the centre of the joint, where the polymer is in a bulky state. Built up on this geometry dependency, the materials ageing as a function of the position is described. To model the change of the polymers state, we use a parameter representing chain scission processes and another one for the reformation of a new network. In a last step, the model is transferred into a finite element code for exemplary calculations.

  16. Aging

    PubMed Central

    Park, Dong Choon

    2013-01-01

    Aging is initiated based on genetic and environmental factors that operate from the time of birth of organisms. Aging induces physiological phenomena such as reduction of cell counts, deterioration of tissue proteins, tissue atrophy, a decrease of the metabolic rate, reduction of body fluids, and calcium metabolism abnormalities, with final progression onto pathological aging. Despite the efforts from many researchers, the progression and the mechanisms of aging are not clearly understood yet. Therefore, the authors would like to introduce several theories which have gained attentions among the published theories up to date; genetic program theory, wear-and-tear theory, telomere theory, endocrine theory, DNA damage hypothesis, error catastrophe theory, the rate of living theory, mitochondrial theory, and free radical theory. Although there have been many studies that have tried to prevent aging and prolong life, here we introduce a couple of theories which have been proven more or less; food, exercise, and diet restriction. PMID:24653904

  17. Aging.

    PubMed

    Park, Dong Choon; Yeo, Seung Geun

    2013-09-01

    Aging is initiated based on genetic and environmental factors that operate from the time of birth of organisms. Aging induces physiological phenomena such as reduction of cell counts, deterioration of tissue proteins, tissue atrophy, a decrease of the metabolic rate, reduction of body fluids, and calcium metabolism abnormalities, with final progression onto pathological aging. Despite the efforts from many researchers, the progression and the mechanisms of aging are not clearly understood yet. Therefore, the authors would like to introduce several theories which have gained attentions among the published theories up to date; genetic program theory, wear-and-tear theory, telomere theory, endocrine theory, DNA damage hypothesis, error catastrophe theory, the rate of living theory, mitochondrial theory, and free radical theory. Although there have been many studies that have tried to prevent aging and prolong life, here we introduce a couple of theories which have been proven more or less; food, exercise, and diet restriction. PMID:24653904

  18. Age structured dynamical model for an endangered lizard Eulamprus leuraensis

    NASA Astrophysics Data System (ADS)

    Supriatna, A. K.; Rachmadani, Q.; Ilahi, F.; Anggriani, N.; Nuraini, N.

    2014-02-01

    The Blue Mountains Water Skink, Eulamprus leuraensis, is listed as an endangered species under the IUCN Red List. This lizard species has a typical characteristic of growth with a low fecundity. It is known that the offspring quality may decline with maternal age of the parents despite they can grow rapidly from neonatal size to adult size within two to three years. It is also believed that low adult survival rates and specialization on rare and fragmented type of habitat are the main cause leading to the endangered status of the lizard. A mathematical model with age structure for Eulamprus leuraensis, taking into account the variation of survival rate in each structure and the declining of offspring quality with respect to maternal age is considered here. Stable coexistence of non-trivial equilibriumis shown. It is also shown that an endangered status is due to combination oflow reproductive output and low rates of adult survival. Further, understanding the age structure within populations can facilitate efective management of the endangered species.

  19. Re-Evaluating Neonatal-Age Models for Ungulates: Does Model Choice Affect Survival Estimates?

    PubMed Central

    Grovenburg, Troy W.; Monteith, Kevin L.; Jacques, Christopher N.; Klaver, Robert W.; DePerno, Christopher S.; Brinkman, Todd J.; Monteith, Kyle B.; Gilbert, Sophie L.; Smith, Joshua B.; Bleich, Vernon C.; Swanson, Christopher C.; Jenks, Jonathan A.

    2014-01-01

    New-hoof growth is regarded as the most reliable metric for predicting age of newborn ungulates, but variation in estimated age among hoof-growth equations that have been developed may affect estimates of survival in staggered-entry models. We used known-age newborns to evaluate variation in age estimates among existing hoof-growth equations and to determine the consequences of that variation on survival estimates. During 2001–2009, we captured and radiocollared 174 newborn (≤24-hrs old) ungulates: 76 white-tailed deer (Odocoileus virginianus) in Minnesota and South Dakota, 61 mule deer (O. hemionus) in California, and 37 pronghorn (Antilocapra americana) in South Dakota. Estimated age of known-age newborns differed among hoof-growth models and varied by >15 days for white-tailed deer, >20 days for mule deer, and >10 days for pronghorn. Accuracy (i.e., the proportion of neonates assigned to the correct age) in aging newborns using published equations ranged from 0.0% to 39.4% in white-tailed deer, 0.0% to 3.3% in mule deer, and was 0.0% for pronghorns. Results of survival modeling indicated that variability in estimates of age-at-capture affected short-term estimates of survival (i.e., 30 days) for white-tailed deer and mule deer, and survival estimates over a longer time frame (i.e., 120 days) for mule deer. Conversely, survival estimates for pronghorn were not affected by estimates of age. Our analyses indicate that modeling survival in daily intervals is too fine a temporal scale when age-at-capture is unknown given the potential inaccuracies among equations used to estimate age of neonates. Instead, weekly survival intervals are more appropriate because most models accurately predicted ages within 1 week of the known age. Variation among results of neonatal-age models on short- and long-term estimates of survival for known-age young emphasizes the importance of selecting an appropriate hoof-growth equation and appropriately defining intervals (i.e., weekly

  20. Re-evaluating neonatal-age models for ungulates: Does model choice affect survival estimates?

    USGS Publications Warehouse

    Grovenburg, Troy W.; Monteith, Kevin L.; Jacques, Christopher N.; Klaver, Robert W.; DePerno, Christopher S.; Brinkman, Todd J.; Monteith, Kyle B.; Gilbert, Sophie L.; Smith, Joshua B.; Bleich, Vernon C.; Swanson, Christopher C.; Jenks, Jonathan A.

    2014-01-01

    New-hoof growth is regarded as the most reliable metric for predicting age of newborn ungulates, but variation in estimated age among hoof-growth equations that have been developed may affect estimates of survival in staggered-entry models. We used known-age newborns to evaluate variation in age estimates among existing hoof-growth equations and to determine the consequences of that variation on survival estimates. During 2001–2009, we captured and radiocollared 174 newborn (≤24-hrs old) ungulates: 76 white-tailed deer (Odocoileus virginianus) in Minnesota and South Dakota, 61 mule deer (O. hemionus) in California, and 37 pronghorn (Antilocapra americana) in South Dakota. Estimated age of known-age newborns differed among hoof-growth models and varied by >15 days for white-tailed deer, >20 days for mule deer, and >10 days for pronghorn. Accuracy (i.e., the proportion of neonates assigned to the correct age) in aging newborns using published equations ranged from 0.0% to 39.4% in white-tailed deer, 0.0% to 3.3% in mule deer, and was 0.0% for pronghorns. Results of survival modeling indicated that variability in estimates of age-at-capture affected short-term estimates of survival (i.e., 30 days) for white-tailed deer and mule deer, and survival estimates over a longer time frame (i.e., 120 days) for mule deer. Conversely, survival estimates for pronghorn were not affected by estimates of age. Our analyses indicate that modeling survival in daily intervals is too fine a temporal scale when age-at-capture is unknown given the potential inaccuracies among equations used to estimate age of neonates. Instead, weekly survival intervals are more appropriate because most models accurately predicted ages within 1 week of the known age. Variation among results of neonatal-age models on short- and long-term estimates of survival for known-age young emphasizes the importance of selecting an appropriate hoof-growth equation and appropriately defining intervals (i.e., weekly

  1. Mixing in age-structured population models of infectious diseases.

    PubMed

    Glasser, John; Feng, Zhilan; Moylan, Andrew; Del Valle, Sara; Castillo-Chavez, Carlos

    2012-01-01

    Infectious diseases are controlled by reducing pathogen replication within or transmission between hosts. Models can reliably evaluate alternative strategies for curtailing transmission, but only if interpersonal mixing is represented realistically. Compartmental modelers commonly use convex combinations of contacts within and among groups of similarly aged individuals, respectively termed preferential and proportionate mixing. Recently published face-to-face conversation and time-use studies suggest that parents and children and co-workers also mix preferentially. As indirect effects arise from the off-diagonal elements of mixing matrices, these observations are exceedingly important. Accordingly, we refined the formula published by Jacquez et al. [19] to account for these newly-observed patterns and estimated age-specific fractions of contacts with each preferred group. As the ages of contemporaries need not be identical nor those of parents and children to differ by exactly the generation time, we also estimated the variances of the Gaussian distributions with which we replaced the Kronecker delta commonly used in theoretical studies. Our formulae reproduce observed patterns and can be used, given contacts, to estimate probabilities of infection on contact, infection rates, and reproduction numbers. As examples, we illustrate these calculations for influenza based on "attack rates" from a prospective household study during the 1957 pandemic and for varicella based on cumulative incidence estimated from a cross-sectional serological survey conducted from 1988-94, together with contact rates from the several face-to-face conversation and time-use studies. Susceptibility to infection on contact generally declines with age, but may be elevated among adolescents and adults with young children. PMID:22037144

  2. AGING PERFORMANCE OF MODEL 9975 PACKAGE FLUOROELASTOMER O-RINGS

    SciTech Connect

    Hoffman, E.; Daugherty, W.; Skidmore, E.; Dunn, K.; Fisher, D.

    2011-05-31

    The influence of temperature and radiation on Viton{reg_sign} GLT and GLT-S fluoroelastomer O-rings is an ongoing research focus at the Savannah River National Laboratory. The O-rings are credited for leaktight containment in the Model 9975 shipping package used for transportation of plutonium-bearing materials. At the Savannah River Site, the Model 9975 packages are being used for interim storage. Primary research efforts have focused on surveillance of O-rings from actual packages, leak testing of seals at bounding aging conditions and the effect of aging temperature on compression stress relaxation behavior, with the goal of service life prediction for long-term storage conditions. Recently, an additional effort to evaluate the effect of aging temperature on the oxidation of the materials has begun. Degradation in the mechanical properties of elastomers is directly related to the oxidation of the polymer. Sensitive measurements of the oxidation rate can be performed in a more timely manner than waiting for a measurable change in mechanical properties, especially at service temperatures. Measuring the oxidation rate therefore provides a means to validate the assumption that the degradation mechanisms(s) do not change from the elevated temperatures used for accelerated aging and the lower service temperatures. Monitoring the amount of oxygen uptake by the material over time at various temperatures can provide increased confidence in lifetime predictions. Preliminary oxygen consumption analysis of a Viton GLT-based fluoroelastomer compound (Parker V0835-75) using an Oxzilla II differential oxygen analyzer in the temperature range of 40-120 C was performed. Early data suggests oxygen consumption rates may level off within the first 100,000 hours (10-12 years) at 40 C and that sharp changes in the degradation mechanism (stress-relaxation) are not expected over the temperature range examined. This is consistent with the known long-term heat aging resistance of

  3. Aging and associative recognition: A view from the DRYAD model of age-related memory deficits.

    PubMed

    Benjamin, Aaron S

    2016-02-01

    How do we best characterize the memory deficits that accompany aging? A popular hypothesis, articulated originally by Naveh-Benjamin (2000) and reviewed in the accompanying article by Smyth and Naveh-Benjamin (2016), suggests that older adults are selectively deficient in establishing associations between to-be-learned memoranda and as a result have deficits in memory for sources or contexts. An alternative proposal, called density of representations yields age-related deficits (DRYAD) and outlined in recent articles by Benjamin (2010) and colleagues (Benjamin, Diaz, Matzen, & Johnson, 2012), attributes disproportionate deficits in memory to a global, rather than a selective, deficit of memory. In an attempt to adjudicate between these competing positions, Smyth and Naveh-Benjamin (2016) discussed 2 sets of experimental data that they claim speak against the global deficit model. Here I review some general principles of how the global-deficit view is applied to experimental paradigms and demonstrate that even a simplified form of DRYAD can comfortably accommodate the critical findings cited by Smyth and Naveh-Benjamin. I also evaluate aspects of their results that may be problematic for DRYAD and describe ways in which DRYAD's account of associative recognition can be falsified. I end with a discussion of the complementary strengths and weaknesses of the 2 approaches and consider ways in which the associative deficit hypothesis and DRYAD might work more profitably together than apart. PMID:26866587

  4. Cognitive aging and hearing acuity: modeling spoken language comprehension

    PubMed Central

    Wingfield, Arthur; Amichetti, Nicole M.; Lash, Amanda

    2015-01-01

    The comprehension of spoken language has been characterized by a number of “local” theories that have focused on specific aspects of the task: models of word recognition, models of selective attention, accounts of thematic role assignment at the sentence level, and so forth. The ease of language understanding (ELU) model (Rönnberg et al., 2013) stands as one of the few attempts to offer a fully encompassing framework for language understanding. In this paper we discuss interactions between perceptual, linguistic, and cognitive factors in spoken language understanding. Central to our presentation is an examination of aspects of the ELU model that apply especially to spoken language comprehension in adult aging, where speed of processing, working memory capacity, and hearing acuity are often compromised. We discuss, in relation to the ELU model, conceptions of working memory and its capacity limitations, the use of linguistic context to aid in speech recognition and the importance of inhibitory control, and language comprehension at the sentence level. Throughout this paper we offer a constructive look at the ELU model; where it is strong and where there are gaps to be filled. PMID:26124724

  5. The OMS3 JGrass-NewAge Environmental Modelling System

    NASA Astrophysics Data System (ADS)

    Formetta, G.; David, O.; Rigon, R.

    2012-12-01

    The need for integrated analysis, and the multiplicity of possible goals in analyses that require hydro-biophysical modelling, necessitates more than ever the capability of composing modelling solutions with parts of known quality, which are transparent to users and consist of reusable model components. Moreover, modern hydrological modelling requires interaction with GIS tools to allow visualizations and the data-processing necessary to synthesise knowledge from high volumes of inputs and outputs data. Last but not least, doing science that is reproducible has requirements that go beyond the computational issues to embrace the possibility to inspection the tools, and easy compare modelling solutions by third party groups. The JGrass-NewAge system was born in order to satisfy these requirements. It is based on the geographic information system uDig-JGrass, and is composed of two parts: (i) the system of visualization of the data and of the results based on uDig; (ii) the modelling components. The latter are implemented as OMS3 components which can be connected or excluded at runtime, according to the needs and works seamlessly inside the uDig Spatial Toolbox. The system is based on a hillslope-link geometrical partition of the landscape, thus the basic unit, where the water budget is evaluated, is the hillslope, and each one of them drains into a single associated link rather than cells or pixels. To this conceptual partition corresponds an implementation of informatics that uses vectorial features for channels, and raster data for hillslopes. The mass budget for each hillslope can be performed in two ways: according to a modification of Duffy dynamical model of hillslope runoff or according to HyMod lumped model. Differently from traditional rainfall-runoff models where the discharge is usually given at the outlet of a catchment, the discharge is evaluated in each link of the river network according to a procedure presented in Cuencas model. The system includes

  6. Overview of Modeling and Simulations of Plutonium Aging

    SciTech Connect

    Schwartz, A J; Wolfer, W G

    2007-04-24

    Computer-aided materials research is now an integral part of science and technology. It becomes particularly valuable when comprehensive experimental investigations and materials testing are too costly, hazardous, or of excessive duration; then, theoretical and computational studies can supplement and enhance the information gained from limited experimental data. Such is the case for improving our fundamental understanding of the properties of aging plutonium in the nuclear weapons stockpile. The question of the effects of plutonium aging on the safety, security, and reliability of the nuclear weapons stockpile emerged after the United States closed its plutonium manufacturing facility in 1989 and decided to suspend any further underground testing of nuclear weapons in 1992. To address this, the Department of Energy's National Nuclear Security Administration (NNSA) initiated a research program to investigate plutonium aging, i.e., the changes with time of properties of Pu-Ga alloys employed in the nuclear weapons and to develop models describing these changes sufficiently reliable to forecast them for several decades. The November 26, 2006 press release by the NNSA summarizes the conclusions of the investigation, '...there appear to be no serious or sudden changes occurring, or expected to occur, in plutonium that would affect performance of pits beyond the well-understood, gradual degradation of plutonium materials'. Furthermore, 'These studies show that the degradation of plutonium in our nuclear weapons will not affect warhead reliability for decades', then NNSA Administrator Linton Brooks said. 'It is now clear that although plutonium aging contributes, other factors control the overall life expectancy of nuclear weapons systems'. The origin of plutonium aging is the natural decay of certain plutonium isotopes. Specifically, it is the process of alpha decay in which a plutonium atom spontaneously splits into a 5 MeV alpha particle and an 85keV uranium recoil

  7. Age-aware solder performance models : level 2 milestone completion.

    SciTech Connect

    Neilsen, Michael K.; Vianco, Paul Thomas; Neidigk, Matthew Aaron; Holm, Elizabeth Ann

    2010-09-01

    Legislated requirements and industry standards are replacing eutectic lead-tin (Pb-Sn) solders with lead-free (Pb-free) solders in future component designs and in replacements and retrofits. Since Pb-free solders have not yet seen service for long periods, their long-term behavior is poorly characterized. Because understanding the reliability of Pb-free solders is critical to supporting the next generation of circuit board designs, it is imperative that we develop, validate and exercise a solder lifetime model that can capture the thermomechanical response of Pb-free solder joints in stockpile components. To this end, an ASC Level 2 milestone was identified for fiscal year 2010: Milestone 3605: Utilize experimentally validated constitutive model for lead-free solder to simulate aging and reliability of solder joints in stockpile components. This report documents the completion of this milestone, including evidence that the milestone completion criteria were met and a summary of the milestone Program Review.

  8. The aging feline kidney: a model mortality antagonist?

    PubMed

    Lawler, Dennis F; Evans, Richard H; Chase, Kevin; Ellersieck, Mark; Li, Qinghong; Larson, Brian T; Satyaraj, Ebenezer; Heininger, Kurt

    2006-12-01

    Traditional thinking views apparently non-programmed disruptions of aging, which medical science calls geriatric diseases, as separate from 'less harmful' morphological and physiological aging phenotypes that are more universally expected with passage of time (loss of skin elasticity, graying of hair coat, weight gain, increased sleep time, behavioral changes, etc). Late-life disease phenotypes, especially those involving chronic processes, frequently are complex and very energy-expensive. A non-programmed process of homeostatic disruption leading into a death trajectory seems inconsistent with energy intensive processes. That is, evolutionary mechanisms do not favor complex and prolonged energy investment in death. Taking a different view, the naturally occurring feline (Felis silvestris catus) renal model suggests that at least some diseases of late life represent only the point of failure in essentially survival-driven adaptive processes. In the feline renal model, individuals that succumbed to failure most frequently displayed progressive tubular deletion and peritubular interstitial fibrosis, but had longer mean life span than cats that died from other causes. Additionally, among cats that died from non-renal causes, those that had degrees of renal tubular deletion and peritubular interstitial fibrosis also had longer mean life span than those cats with no changes, even though causes of death differed minimally between these latter two groups. The data indicate that selective tubular deletion very frequently begins early in adult life, without a clear initiating phase or event. The observations support a hypothesis that this prolonged process may be intrinsic and protective prior to an ultimate point of failure. Moreover, given the genetic complexity and the interplay with associated risk factors, existing data also do not support the ideas that these changes are simple compensatory responses and that breed- or strain-based 'default' diseases are inevitable

  9. Effect of Age of Models in Print Ads on Evaluation of Product and Sponsor.

    ERIC Educational Resources Information Center

    Rotfeld, Herbert J.; And Others

    1982-01-01

    Details a study that investigated how middle-aged housewives responded to different age portrayals for different age-oriented products in advertisements. Concludes that there was a clear interaction between age-orientation of product and age of model in an advertisement, but no pervasive "younger is better" effect. (FL)

  10. Modeling Diverse Pathways to Age Progressive Volcanism in Subduction Zones.

    NASA Astrophysics Data System (ADS)

    Kincaid, C. R.; Szwaja, S.; Sylvia, R. T.; Druken, K. A.

    2015-12-01

    One of the best, and most challenging clues to unraveling mantle circulation patterns in subduction zones comes in the form of age progressive volcanic and geochemical trends. Hard fought geological data from many subduction zones, like Tonga-Lau, the Cascades and Costa-Rica/Nicaragua, reveal striking temporal patterns used in defining mantle flow directions and rates. We summarize results from laboratory subduction models showing a range in circulation and thermal-chemical transport processes. These interaction styles are capable of producing such trends, often reflecting apparent instead of actual mantle velocities. Lab experiments use a glucose working fluid to represent Earth's upper mantle and kinematically driven plates to produce a range in slab sinking and related wedge transport patterns. Kinematic forcing assumes most of the super-adiabatic temperature gradient available to drive major downwellings is in the tabular slabs. Moreover, sinking styles for fully dynamic subduction depend on many complicating factors that are only poorly understood and which can vary widely even for repeated parameter combinations. Kinematic models have the benefit of precise, repeatable control of slab motions and wedge flow responses. Results generated with these techniques show the evolution of near-surface thermal-chemical-rheological heterogeneities leads to age progressive surface expressions in a variety of ways. One set of experiments shows that rollback and back-arc extension combine to produce distinct modes of linear, age progressive melt delivery to the surface through a) erosion of the rheological boundary layer beneath the overriding plate, and deformation and redistribution of both b) mantle residuum produced from decompression melting and c) formerly active, buoyant plumes. Additional experiments consider buoyant diapirs rising in a wedge under the influence of rollback, back-arc spreading and slab-gaps. Strongly deflected diapirs, experiencing variable rise

  11. A micrometeorite erosion model and the age of Saturn's rings

    NASA Technical Reports Server (NTRS)

    Northrop, T. G.; Connerney, J. E. P.

    1987-01-01

    An erosional model of Saturn's rings is proposed based on theoretical studies of the high charge-to-mass ratio particles in Saturn's ring plane, and assuming that the B and C rings were initially formed as one ring with the optical thickness of the present B ring. The erosion rate is calculated using data from observed micrometeorite fluxes, and a ring age of 4.4-76 Myr is determined which is inconsistent with the 4.5-Gyr ring lifetime required by the cosmogonic ring hypothesis. The sharpness of the transition between the B and C rings suggests that the principal mass loss is through particles moving at a few m/sec with respect to the parent bodies from which they were eroded.

  12. Ploidy, sex and crossing over in an evolutionary aging model

    NASA Astrophysics Data System (ADS)

    Lobo, Matheus P.; Onody, Roberto N.

    2006-02-01

    Nowadays, many forms of reproduction coexist in nature: Asexual, sexual, apomictic and meiotic parthenogenesis, hermaphroditism and parasex. The mechanisms of their evolution and what made them successful reproductive alternatives are very challenging and debated questions. Here, using a simple evolutionary aging model, we give a possible scenario. By studying the performance of populations where individuals may have diverse characteristics-different ploidies, sex with or without crossing over, as well as the absence of sex-we find an evolution sequence that may explain why there are actually two major or leading groups: Sexual and asexual. We also investigate the dependence of these characteristics on different conditions of fertility and deleterious mutations. Finally, if the primeval organisms on Earth were, in fact, asexual individuals we conjecture that the sexual form of reproduction could have more easily been set and found its niche during a period of low-intensity mutations.

  13. Cellular models and therapies for age-related macular degeneration

    PubMed Central

    Forest, David L.; Johnson, Lincoln V.; Clegg, Dennis O.

    2015-01-01

    ABSTRACT Age-related macular degeneration (AMD) is a complex neurodegenerative visual disorder that causes profound physical and psychosocial effects. Visual impairment in AMD is caused by the loss of retinal pigmented epithelium (RPE) cells and the light-sensitive photoreceptor cells that they support. There is currently no effective treatment for the most common form of this disease (dry AMD). A new approach to treating AMD involves the transplantation of RPE cells derived from either human embryonic or induced pluripotent stem cells. Multiple clinical trials are being initiated using a variety of cell therapies. Although many animal models are available for AMD research, most do not recapitulate all aspects of the disease, hampering progress. However, the use of cultured RPE cells in AMD research is well established and, indeed, some of the more recently described RPE-based models show promise for investigating the molecular mechanisms of AMD and for screening drug candidates. Here, we discuss innovative cell-culture models of AMD and emerging stem-cell-based therapies for the treatment of this vision-robbing disease. PMID:26035859

  14. Age-Related Effects of Alcohol from Adolescent, Adult, and Aged Populations Using Human and Animal Models

    PubMed Central

    Squeglia, Lindsay M.; Boissoneault, Jeff; Van Skike, Candice E.; Nixon, Sara Jo; Matthews, Douglas B.

    2014-01-01

    Background This review incorporates current research examining alcohol's differential effects on adolescents, adults, and aged populations in both animal and clinical models. Methods The studies presented range from cognitive, behavioral, molecular, and neuroimaging techniques, leading to a more comprehensive understanding of how acute and chronic alcohol use affects the brain throughout the life span. Results Age of life is a significant factor in determining the effect of alcohol on brain functioning. Adolescents and aged populations may be more negatively affected by heavy alcohol use when compared to adults. Conclusions Investigations limiting alcohol effects to a single age group constrains understanding of differential trajectories and outcomes following acute and chronic use. To meaningfully address the sequencing and interaction effects of alcohol and age, the field must incorporate collaborative and integrated research efforts focused on interdisciplinary questions facilitated by engaging basic and applied scientists with expertise in a range of disciplines including alcohol, neurodevelopment, and aging. PMID:25156779

  15. Radiocarbon ages and age models for the past 30,000 years in Bear Lake, Utah and Idaho

    USGS Publications Warehouse

    Colman, Steven M.; Rosenbaum, J.G.; Kaufman, D.S.; Dean, W.E.; McGeehin, J.P.

    2009-01-01

    Radiocarbon analyses of pollen, ostracodes, and total organic carbon (TOC) provide a reliable chronology for the sediments deposited in Bear Lake over the past 30,000 years. The differences in apparent age between TOC, pollen, and carbonate fractions are consistent and in accord with the origins of these fractions. Comparisons among different fractions indicate that pollen sample ages are the most reliable, at least for the past 15,000 years. The post-glacial radiocarbon data also agree with ages independently estimated from aspartic acid racemization in ostracodes. Ages in the red, siliclastic unit, inferred to be of last glacial age, appear to be several thousand years too old, probably because of a high proportion of reworked, refractory organic carbon in the pollen samples. Age-depth models for five piston cores and the Bear Lake drill core (BL00-1) were constructed by using two methods: quadratic equations and smooth cubic-splinefits. The two types of age models differ only in detail for individual cores, and each approach has its own advantages. Specific lithological horizons were dated in several cores and correlated among them, producing robust average ages for these horizons. The age of the correlated horizons in the red, siliclastic unit can be estimated from the age model for BL00-1, which is controlled by ages above and below the red, siliclastic unit. These ages were then transferred to the correlative horizons in the shorter piston cores, providing control for the sections of the age models in those cores in the red, siliclastic unit. These age models are the backbone for reconstructions of past environmental conditions in Bear Lake. In general, sedimentation rates in Bear Lake have been quite uniform, mostly between 0.3 and 0.8 mm yr-1 in the Holocene, and close to 0.5 mm yr-1 for the longer sedimentary record in the drill core from the deepest part of the lake. Copyright ?? 2009 The Geological Society of America.

  16. Oxidative Stress, Aging and CNS disease in the Canine Model of Human Brain Aging

    PubMed Central

    Head, Elizabeth; Rofina, Jaime; Zicker, Steven

    2008-01-01

    SYNOPSIS Decline in cognitive functions that accompany aging in dogs may have a biological basis, and many of the disorders associated with aging in canines may be mitigated through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of both laboratory and clinical studies – antioxidants may be one class of nutraceutical that provides benefits to aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which may lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes may lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs. However, determining all effective compounds and combinations, dosage ranges, as well as when to initiate intervention and long term effects constitute gaps in our current knowledge. PMID:18249248

  17. Modeling dynamic strain aging of aluminum-magnesium alloys

    NASA Astrophysics Data System (ADS)

    Zhang, Dawei

    This thesis presents atomistic studies and continuum modeling of solute clustering and solute diffusion in Al-Mg alloys, which are considered elements of the mechanism of dynamic strain aging (DSA). Solute clustering in Al-Mg binary alloys is first studied by means of Monte-Carlo simulations. In the undistorted lattice, Mg has a tendency to form a coherent phase. The binding energy of this structure is rather low and it dissolves at room temperature when only dynamic associations of doublets or triples of solute atoms are observed. In presence of dislocations and at room temperature, Mg clusters at cores forming the coherent phase observed in the undistorted lattice at lower temperatures. The size, shape and structure of the cluster cannot be predicted by elementary calculations based on the pressure field generated by the unclustered dislocation. Then diffusion for Mg in Al-Mg alloys is investigated by Molecular Statics and the Nudged Elastic Band method. The activation energy for diffusion of Mg in the bulk is evaluated in the dilute solution limit for the nearest neighbor and the ring mechanisms. It is concluded that bulk diffusion at low and moderate temperatures must be assisted by vacancies. Further, diffusion of Mg along the core of edge, 60° and screw dislocations is studied. The vacancy formation energy in the core and the migration energy for vacancy-assisted Mg is evaluated for a large number of diffusion paths in the core region. The analysis shows that pipe diffusion; which is currently considered as the leading mechanism responsible for dynamic strain aging in these alloys, is too slow in absence of excess vacancies. Finally, the time-dependent Mg solute clustering process is studied using a continuum model calibrated based on atomistic information. The solute atmosphere around an edge dislocation is evaluated in terms of a chemical potential gradient, which is obtained from Monte-Carlo simulations. The solute clustering process is modeled by coupled

  18. Sensitivity analysis of the age-structured malaria transmission model

    NASA Astrophysics Data System (ADS)

    Addawe, Joel M.; Lope, Jose Ernie C.

    2012-09-01

    We propose an age-structured malaria transmission model and perform sensitivity analyses to determine the relative importance of model parameters to disease transmission. We subdivide the human population into two: preschool humans (below 5 years) and the rest of the human population (above 5 years). We then consider two sets of baseline parameters, one for areas of high transmission and the other for areas of low transmission. We compute the sensitivity indices of the reproductive number and the endemic equilibrium point with respect to the two sets of baseline parameters. Our simulations reveal that in areas of either high or low transmission, the reproductive number is most sensitive to the number of bites by a female mosquito on the rest of the human population. For areas of low transmission, we find that the equilibrium proportion of infectious pre-school humans is most sensitive to the number of bites by a female mosquito. For the rest of the human population it is most sensitive to the rate of acquiring temporary immunity. In areas of high transmission, the equilibrium proportion of infectious pre-school humans and the rest of the human population are both most sensitive to the birth rate of humans. This suggests that strategies that target the mosquito biting rate on pre-school humans and those that shortens the time in acquiring immunity can be successful in preventing the spread of malaria.

  19. Investigating lower stratospheric model transport: Lagrangian calculations of mean age and age spectra in the GCM ECHAM4

    NASA Astrophysics Data System (ADS)

    Reithmeier, Christian; Sausen, Robert; Grewe, Volker

    2008-02-01

    The Lagrangian scheme ATTILA is used to calculate age spectra and the mean age of air in the general circulation model ECHAM4. The advantage of the Lagrangian method is that temporal variation in transport is taken into account and that beyond transport times the actual transport pathways can be investigated. We found a strong seasonal cycle in mean age and age spectra, especially at high latitudes. When plotting polar age spectra against time, it can clearly be seen that the edge of the polar vortex acts as an efficient transport barrier and that exchange with extra-polar air takes place only for a short period of approximately two months after the polar vortex has broken down. Compared to observations the mean age is reproduced satisfactorily below approximately 20 km. Above that level however, the mean age is underestimated, especially at high latitudes. Furthermore, the observed sharp meridional gradient is located too far polewards in the model, which indicates that the subtropical transport barrier is too weak. There is a distinct variation in the shape of the age spectra with latitude. At low latitudes the age spectra consist of one single peak, whereas at higher latitudes secondary peaks appear, which are one year apart and whose positions in the spectrum are independent of the location. At polar latitudes there are even several peaks of approximately equal size. We explain these peaks with two superposing processes. First, the seasonal cycle of the upward mass flux at the tropical tropopause produces a single peak age distribution. And second, at polar latitudes, the temporal evolution of the polar vortex allows mixing of polar and subtropical air only once a year, which results in a superposition of these single peak age distributions. A final investigation of the transport pathways gave indications for predominant routes from the tropics to high latitudes resulting in altitude dependent meridional transport, however, more detailed studies of 3D

  20. Aging Through Hierarchical Coalescence in the East Model

    NASA Astrophysics Data System (ADS)

    Faggionato, A.; Martinelli, F.; Roberto, C.; Toninelli, C.

    2012-01-01

    We rigorously analyze the low temperature non-equilibrium dynamics of the East model, a special example of a one dimensional oriented kinetically constrained particle model, when the initial distribution is different from the reversible one and for times much smaller than the global relaxation time. This setting has been intensively studied in the physics literature to analyze the slow dynamics which follows a sudden quench from the liquid to the glass phase. In the limit of zero temperature (i.e. a vanishing density of vacancies) and for initial distributions such that the vacancies form a renewal process, we prove that the density of vacancies, the persistence function and the two-time autocorrelation function behave as staircase functions with several plateaux. Furthermore the two-time autocorrelation function displays an aging behavior. We also provide a sharp description of the statistics of the domain length as a function of time, a domain being the interval between two consecutive vacancies. When the initial renewal process has finite mean, our results confirm (and generalize) previous findings of the physicists for the restricted case of a product Bernoulli measure. However we show that a different behavior appears when the initial domain distribution is in the attraction domain of a α-stable law. All the above results actually follow from a more general result which says that the low temperature dynamics of the East model is very well described by that of a certain hierarchical coalescence process, a probabilistic object which can be viewed as a hierarchical sequence of suitably linked coalescence processes and whose asymptotic behavior has been recently studied in Faggionato et al. (Universality in one dimensional hierarchical 1059 coalescence processes. Preprint, 2011).

  1. Constraining age and rate of deformation in the northern Bolivian Andes from cross sections, cooling ages, and thermokinematic modeling

    NASA Astrophysics Data System (ADS)

    McQuarrie, N.; Ehlers, T. A.; Rak, A. J.

    2015-12-01

    A critical component in assessing the viability of proposed plate tectonic or geodynamic processes in regions of convergence is the expected or predicted age and rate of deformation in the overriding plate. Commonly, age of deformation is inferred through geochronology of foreland basin and wedge-top sedimentary rocks and bedrock thermochronometer cooling signals. In Bolivia the original pulse of deformation of the fold-thrust belt is argue to be as young as 38-25 Ma based on the age of synorogenic strata or as old as 65-45 Ma due to proposed foreland basin rocks deposited in the Bolivian Altiplano. The large discrepancies in proposed age, rate and magnitude of deformation through the Bolivian Andes limit our ability to relate age and rate of shortening to internal geodynamic or external plate tectonic processes. We evaluate permissible ranges in age of initiation and rate of deformation through a forward kinematic model of the northern Bolivian fold-thrust belt. Each step of deformation accounts for isostatic loading from thrust faults and subsequent erosional of structural highs. The kinematic model predicts an evolution of flexural basins into which synorogenic sediments are deposited allowing us to fully integrate age of exhumation and deposition to age and magnitude of deformation. By assigning an age to each deformation step, we create a range of velocity vectors that are input into the thermokinematic model Pecube, which predicts thermochronometer cooling histories based on kinematics, topography, thermal parameters and shortening rates. We match the pattern of predicted ages with the across strike pattern of measured zircon fission track, apatite fission track and apatite (U-Th)/ He cooling ages. The sensitivity of modeled thermochronologic data to the age at which deformation initiates indicate that northern Bolivian EC started deforming at 50 Ma and may have begun as early as 55 Ma. The acceptable velocity envelope for the modeled section permits either a

  2. U.S. Telecommunications and Trade Policies: The Need for an Effective Information Age Model.

    ERIC Educational Resources Information Center

    Tirman, W. Robert

    This paper examines the need for telecommunications and international trade policies in the Information Age and presents a model for developing such policies. The first of seven sections discusses the need for an Information Age Model, and the technological changes that are giving rise to increasingly integrated Information Age networks are…

  3. Characterizing cognitive aging in humans with links to animal models

    PubMed Central

    Alexander, Gene E.; Ryan, Lee; Bowers, Dawn; Foster, Thomas C.; Bizon, Jennifer L.; Geldmacher, David S.; Glisky, Elizabeth L.

    2012-01-01

    With the population of older adults expected to grow rapidly over the next two decades, it has become increasingly important to advance research efforts to elucidate the mechanisms associated with cognitive aging, with the ultimate goal of developing effective interventions and prevention therapies. Although there has been a vast research literature on the use of cognitive tests to evaluate the effects of aging and age-related neurodegenerative disease, the need for a set of standardized measures to characterize the cognitive profiles specific to healthy aging has been widely recognized. Here we present a review of selected methods and approaches that have been applied in human research studies to evaluate the effects of aging on cognition, including executive function, memory, processing speed, language, and visuospatial function. The effects of healthy aging on each of these cognitive domains are discussed with examples from cognitive/experimental and clinical/neuropsychological approaches. Further, we consider those measures that have clear conceptual and methodological links to tasks currently in use for non-human animal studies of aging, as well as those that have the potential for translation to animal aging research. Having a complementary set of measures to assess the cognitive profiles of healthy aging across species provides a unique opportunity to enhance research efforts for cross-sectional, longitudinal, and intervention studies of cognitive aging. Taking a cross-species, translational approach will help to advance cognitive aging research, leading to a greater understanding of associated neurobiological mechanisms with the potential for developing effective interventions and prevention therapies for age-related cognitive decline. PMID:22988439

  4. Ages estimated from a diffusion equation model for scarp degradation

    USGS Publications Warehouse

    Colman, Steven M.; Watson, K.E.N.

    1983-01-01

    The diffusion equation derived from the continuity equation for hillslopes is applied to scarp erosion in unconsolidated materials. Solutions to this equation allow direct calculation of the product of the rate coefficient and the age of the scarp from measurements of scarp morphology. Where the rate coefficient can be estimated or can be derived from scarps of known age, this method allows direct calculation of unknown ages of scarps.

  5. Four-vessel occlusion model using aged male Wistar rats: a reliable model to resolve the discrepancy related to age in cerebral ischemia research.

    PubMed

    Ancer-Rodríguez, Jesús; Villarreal-Silva, Eliud Enrique; Salazar-Ybarra, Rodolfo Amador; Quiroga-García, Oscar; Rodríguez-Rocha, Humberto; García-García, Aracely; Morales-Avalos, Rodolfo; Morales-Gómez, Jesús Alberto; Quiroga-Garza, Alejandro; Saucedo-Cárdenas, Odila; Xu, Zao Cheng; Elizondo-Omaña, Rodrigo Enrique; Martínez-Ponce-de-León, Angel Raymundo; Guzmán-López, Santos

    2016-06-01

    Animal models of cerebral ischemia have typically been established and performed using young animals, even though cerebral ischemia (CI) affects primarily elderly patients. This situation represents a discrepancy that complicates the translation of novel therapeutic strategies for CI. Models of transient global CI using aged animals have demonstrated an apparent neuroprotective effect on CA1 hippocampal neurons; however, this effect is not completely understood. Our study used a model in which young (3-6 months) and aged (18-21 months) male Wistar rats were subjected to 15 min of transient global CI using the four-vessel occlusion (4 VO) model. We determined that the 4 VO model can be performed on aged rats with a slight increase in mortality rate. In aged rats, the morphological damage was completely established by the 4th day after reperfusion, displaying no difference from their younger counterparts. These results demonstrated the lack of a neuroprotective effect of aging on CA1 hippocampal neurons in aged male Wistar rats. This study determined and characterized the morphological damage to the CA1 area after 15 min of 4 VO in aged male Wistar rats, validating the use of this model in CI and aging research. PMID:25966656

  6. Continuous Age-Structured Model for Bovine Tuberculosis in African buffalo

    NASA Astrophysics Data System (ADS)

    Anguelov, R.; Kojouharov, H.

    2009-10-01

    The paper deals with a model of the spread of bovine tuberculosis in the buffalo population in the Kruger National Park in South Africa. The model uses continuous age structure and it is formulated in terms of partial differential equations using eight epidemiological classes (compartments). More precisely, the age density for each class at time t satisfies a one way wave equation, where the age is the space variable. The continuous age model discussed here is derived from a 2006 age groups model by P. C. Cross and W. M. Getz.

  7. Towards a unified and interdisciplinary model of ageing.

    PubMed

    Jameson, C W

    2004-01-01

    Researchers currently disagree about the appropriate biomarkers to monitor when measuring the ageing process. The major problem is identifying symptoms that are an end in and of themselves, from symptoms that are tied directly to the root cause, or causes, of ageing. This is most likely the reason that numerous, diverse and plausible theories for ageing co-exist. When young and old nuclei are exchanged between cells, the age of the resulting cell correlated with the nucleus. This suggests a large role of the nucleus as the target of ageing, although the sources of ageing may originate externally. There are three processes that occur when eukaryotes age. They are: (1) a progressive and patterned alteration of the structure of chromosomes after young adulthood has been reached, (2) a progressive and patterned malfunction of the degradation systems, and (3) age-altered post-translational modifications of proteins. A change in any one of these processes often causes a ripple effect that affects the other two processes. This paper begins by stating that the above three processes are the appropriate biomarkers of ageing. These three processes are coordinated with one another under normal physiological conditions. For example, proteasomes and their subunits have been found to regulate excision repair, transcription, and the turnover of nuclear/cytoplasmic receptors. The degradation system is also responsible for the removal of oxidized histones and other factors, which influence chromosome structure. Regulatory post-translational modifications at the histone level include methylation, phosphorylation, and acetylation. In addition, the above three processes undergo age related changes. Some of these modifications represent valid responses by the cell, but many do not. The effect of these age-altered macromolecules is perverse and unpredictable. For example, the cell's age-compromised degradation allows the accumulation of signaling complexes, which no longer match the

  8. The short-lived African turquoise killifish: an emerging experimental model for ageing.

    PubMed

    Kim, Yumi; Nam, Hong Gil; Valenzano, Dario Riccardo

    2016-02-01

    Human ageing is a fundamental biological process that leads to functional decay, increased risk for various diseases and, ultimately, death. Some of the basic biological mechanisms underlying human ageing are shared with other organisms; thus, animal models have been invaluable in providing key mechanistic and molecular insights into the common bases of biological ageing. In this Review, we briefly summarise the major applications of the most commonly used model organisms adopted in ageing research and highlight their relevance in understanding human ageing. We compare the strengths and limitations of different model organisms and discuss in detail an emerging ageing model, the short-lived African turquoise killifish. We review the recent progress made in using the turquoise killifish to study the biology of ageing and discuss potential future applications of this promising animal model. PMID:26839399

  9. The short-lived African turquoise killifish: an emerging experimental model for ageing

    PubMed Central

    Kim, Yumi; Nam, Hong Gil; Valenzano, Dario Riccardo

    2016-01-01

    ABSTRACT Human ageing is a fundamental biological process that leads to functional decay, increased risk for various diseases and, ultimately, death. Some of the basic biological mechanisms underlying human ageing are shared with other organisms; thus, animal models have been invaluable in providing key mechanistic and molecular insights into the common bases of biological ageing. In this Review, we briefly summarise the major applications of the most commonly used model organisms adopted in ageing research and highlight their relevance in understanding human ageing. We compare the strengths and limitations of different model organisms and discuss in detail an emerging ageing model, the short-lived African turquoise killifish. We review the recent progress made in using the turquoise killifish to study the biology of ageing and discuss potential future applications of this promising animal model. PMID:26839399

  10. An agent-based computational model for tuberculosis spreading on age-structured populations

    NASA Astrophysics Data System (ADS)

    Graciani Rodrigues, C. C.; Espíndola, Aquino L.; Penna, T. J. P.

    2015-06-01

    In this work we present an agent-based computational model to study the spreading of the tuberculosis (TB) disease on age-structured populations. The model proposed is a merge of two previous models: an agent-based computational model for the spreading of tuberculosis and a bit-string model for biological aging. The combination of TB with the population aging, reproduces the coexistence of health states, as seen in real populations. In addition, the universal exponential behavior of mortalities curves is still preserved. Finally, the population distribution as function of age shows the prevalence of TB mostly in elders, for high efficacy treatments.

  11. Urban groundwater age modeling under unconfined condition - Impact of underground structures on groundwater age: Evidence of a piston effect

    NASA Astrophysics Data System (ADS)

    Attard, Guillaume; Rossier, Yvan; Eisenlohr, Laurent

    2016-04-01

    In this paper, underground structures are shown to have a major influence on the groundwater mean age distribution described as a dispersive piston effect. Urban underground development does not occur without impacts on subsoil resources. In particular, groundwater resources can be vulnerable and generate disturbances when this space is exploited. Groundwater age spatial distribution data are fundamental for resource management as it can provide operational sustainability indicators. However, the application of groundwater age modeling is neglected regarding the potential effect of underground structures in urban areas. A three dimensional modeling approach was conducted to quantify the impact of two underground structures: (1) an impervious structure and (2) a draining structure. Both structures are shown to cause significant mixing processes occurring between shallow and deeper aquifers. The design technique used for draining structures is shown to have the greatest impact, generating a decrease in mean age of more than 80% under the structure. Groundwater age modeling is shown to be relevant for highlighting the role played by underground structures in advective-dispersive flows in urban areas.

  12. Modelling aging effects on a thermal cycling absorption process column

    SciTech Connect

    Laquerbe, C.; Contreras, S.; Demoment, J.

    2008-07-15

    Palladium coated on alumina is used in hydrogen separation systems operated at CEA/Valduc, and more particularly in Thermal Cycling Absorption Process columns. With such materials, tritium decay is known to induce aging effects which have direct side effects on hydrogen isotopes absorption isotherms. Furthermore in a TCAP column, aging occurs in an heterogeneous way. The possible impacts of these intrinsic material evolutions on the separation performances are investigated here through a numerical approach. (authors)

  13. Reinvestigation of age model for relative paleointensity stack and application to Lake Baikal record

    NASA Astrophysics Data System (ADS)

    Oda, H.

    2014-12-01

    The age model for relative paleointensity stack PISO-1500 (Channell et al., 2009) is based on IODP U1308 from North Atlantic. Channell et al. (2008) developed the age model for U1308 by correlating the benthic oxygen isotope curve with LR04 oxygen isotope stack (Lisiecki&Raymo, 2005). LR04 stack is known as oxygen isotope stack for benthic foraminifarra, whose age model is dependent on ice volume model with a certain time lag. On the other hand, Caballero-Gill et al. (2012) developed an absolute age model based on U-Th dating for stalagmites from China and correlated the oxygen isotope curve with that on planctonic foraminiferra for a deep-sea core from South China Sea. The age model based on absolute dating for stalagmite was then transfered to oxygen isotope curve of benthic forraminiferra for the same core. This enables to provide absolute age model on PISO-1500 for the past 350 kyrs. The resulting modified PISO-1500 was applied on paleomagnetic records from Lake Baikal to provide an age model based on relative paleointensity. Finally, this age model was compared with alternative age model based on correlation of biogenic silica record with insolation at the site (Prokopenko et al., 2006) and the reason for the discrepancy will be discussed.

  14. Aging and Neurodegeneration: A Tangle of Models and Mechanisms.

    PubMed

    Chakrabarti, Sasanka; Mohanakumar, Kochupurackal P

    2016-03-01

    The research on aging and age-related diseases, especially the neurodegenerative diseases, is on the fast track. However, the results have so far not been translated to actual benefit for the patients in terms of treatment or diagnosis of age-related degenerative diseases including those of the CNS. As far as the prevention of the cognitive decline during non-pathological aging is concerned, there is nothing much to offer other than calorie restriction and physical exercise. Needless to say, the benefits are not up to our expectations. However, over the years at the experimental level it has been possible to identify several cellular and molecular mechanisms that are intricately associated with aging in general and neurodegenerative diseases in particular. These include oxidative stress and altered redox-signaling, mitochondrial dysfunction, inflammation, proteotoxicity and altered gene expressions. These inter-dependent pathways mediate cellular senescence and often culminate in programmed cell death like apoptosis and autophagy, and in the context of brain these changes are manifested clinically as cognitive decline and pathologically as neurodegeneration. This special issue provides the readers with glimpses of this complex scenario from different angles primarily in the context of brain and also attempts to identify the potential drug targets against neurodegenerative diseases. PMID:27114843

  15. Aging and Neurodegeneration: A Tangle of Models and Mechanisms

    PubMed Central

    Chakrabarti, Sasanka; Mohanakumar, Kochupurackal P.

    2016-01-01

    The research on aging and age-related diseases, especially the neurodegenerative diseases, is on the fast track. However, the results have so far not been translated to actual benefit for the patients in terms of treatment or diagnosis of age-related degenerative diseases including those of the CNS. As far as the prevention of the cognitive decline during non-pathological aging is concerned, there is nothing much to offer other than calorie restriction and physical exercise. Needless to say, the benefits are not up to our expectations. However, over the years at the experimental level it has been possible to identify several cellular and molecular mechanisms that are intricately associated with aging in general and neurodegenerative diseases in particular. These include oxidative stress and altered redox-signaling, mitochondrial dysfunction, inflammation, proteotoxicity and altered gene expressions. These inter-dependent pathways mediate cellular senescence and often culminate in programmed cell death like apoptosis and autophagy, and in the context of brain these changes are manifested clinically as cognitive decline and pathologically as neurodegeneration. This special issue provides the readers with glimpses of this complex scenario from different angles primarily in the context of brain and also attempts to identify the potential drug targets against neurodegenerative diseases. PMID:27114843

  16. Abnormal glutamate release in aged BTBR mouse model of autism

    PubMed Central

    Wei, Hongen; Ding, Caiyun; Jin, Guorong; Yin, Haizhen; Liu, Jianrong; Hu, Fengyun

    2015-01-01

    Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. Most of the available research on autism is focused on children and young adults and little is known about the pathological alternation of autism in older adults. In order to investigate the neurobiological alternation of autism in old age stage, we compared the morphology and synaptic function of excitatory synapses between the BTBR mice with low level sociability and B6 mice with high level sociability. The results revealed that the number of excitatory synapse colocalized with pre- and post-synaptic marker was not different between aged BTBR and B6 mice. The aged BTBR mice had a normal structure of dendritic spine and the expression of Shank3 protein in the brain as well as that in B6 mice. The baseline and KCl-evoked glutamate release from the cortical synaptoneurosome in aged BTBR mice was lower than that in aged B6 mice. Overall, the data indicate that there is a link between disturbances of the glutamate transmission and autism. These findings provide new evidences for the hypothesis of excitation/inhibition imbalance in autism. Further work is required to determine the cause of this putative abnormality. PMID:26617779

  17. NMR and molecular modeling: application to wine ageing

    NASA Astrophysics Data System (ADS)

    Saucier, C.; Pianet, I.; Laguerre, M.; Glories, Y.

    1998-02-01

    Red wine contains polyphenols called tannins which are very important for its taste and longevity. These polymers consist in repeating units of catechin and its epimer epicatechin. During ageing, slow condensation reactions take place which lead to new chemical structures. Among the possible reactions, we have focused our attention on acetaldehyde cross-linking. Catechin was used as a model for the production of polymers with acetaldehyde. Two reaction product fractions have been isolated by liquid chromatography. Mass measurement indicated that these fractions contain dimers. NMR (1D and 2D) and molecular modelling were then used to study the structure and conformations of these products. The first product consist in a pure dimer with the two catechin moieties connected with an ethyl bridge on the carbon 6 and 8. The second fraction was a mixture of two dimers (50/50). NMR measurements showed that it could be two symmetrical dimers involving the same carbon for each catechin moiety (6 or8). Le vin rouge contient des polyphénols appelés tanins qui sont très importants pour son goût et sa longévité. Il s'agit principalement de polymères de catéchine et d'épicatéchine. Durant le vieillissement du vin, des réactions de condensation interviennent lentement et conduisent à de nouvelles structures. Parmi les réactions possibles, nous avons plus spécialement étudié la polymérisation par pontage avec l'éthanal. La catéchine a été utilisée comme modèle de tannin et mise en présence d'éthanal en milieu acide proche du vin. Deux fractions de produits de réaction ont été isolées par chromatographie liquide. La spectrométrie de masse a révélé la présence de dimères. La RMN (1D et 2D) et la modélisation moléculaire ont ensuite été utilisées pour déterminer la structure et la conformation de ces produits. La première fraction a été identifiée comme étant un dimère de deux unités catéchines reliées par un pont éthyle par leur

  18. Aging and Predicting Inferences: A Diffusion Model Analysis

    ERIC Educational Resources Information Center

    McKoon, Gail; Ratcliff, Roger

    2013-01-01

    In the domain of discourse processing, it has been claimed that older adults (60-0-year-olds) are less likely to encode and remember some kinds of information from texts than young adults. The experiment described here shows that they do make a particular kind of inference to the same extent that college-age adults do. The inferences examined were…

  19. An Age-Graded Model for Career Development Education

    ERIC Educational Resources Information Center

    Tuckman, Bruce W.

    1974-01-01

    This paper attempts to provide a framework by which educators interested in stimulating career development can choose the learning experiences most likely to have payoffs for different age youth. Eight stages of child development are described with career development themes suggested for each stage along with sample activities. (Author)

  20. An Attachment Model of Sibling Helping Behavior in Old Age.

    ERIC Educational Resources Information Center

    Cicirelli, Victor G.

    Sibling relationships are not only maintained throughout life in most cases, but assume considerable importance in old age. Siblings provide psychological support for each other as well as more tangible forms of helping and caregiving. In order to investigate variables leading to sibling help in the area of psychological support, a path model…

  1. Phospholipase A2 – nexus of aging, oxidative stress, neuronal excitability, and functional decline of the aging nervous system? Insights from a snail model system of neuronal aging and age-associated memory impairment

    PubMed Central

    Hermann, Petra M.; Watson, Shawn N.; Wildering, Willem C.

    2014-01-01

    The aging brain undergoes a range of changes varying from subtle structural and physiological changes causing only minor functional decline under healthy normal aging conditions, to severe cognitive or neurological impairment associated with extensive loss of neurons and circuits due to age-associated neurodegenerative disease conditions. Understanding how biological aging processes affect the brain and how they contribute to the onset and progress of age-associated neurodegenerative diseases is a core research goal in contemporary neuroscience. This review focuses on the idea that changes in intrinsic neuronal electrical excitability associated with (per)oxidation of membrane lipids and activation of phospholipase A2 (PLA2) enzymes are an important mechanism of learning and memory failure under normal aging conditions. Specifically, in the context of this special issue on the biology of cognitive aging we portray the opportunities offered by the identifiable neurons and behaviorally characterized neural circuits of the freshwater snail Lymnaea stagnalis in neuronal aging research and recapitulate recent insights indicating a key role of lipid peroxidation-induced PLA2 as instruments of aging, oxidative stress and inflammation in age-associated neuronal and memory impairment in this model system. The findings are discussed in view of accumulating evidence suggesting involvement of analogous mechanisms in the etiology of age-associated dysfunction and disease of the human and mammalian brain. PMID:25538730

  2. All age-depth models are wrong, but are getting better

    NASA Astrophysics Data System (ADS)

    Trachsel, Mathias; Chipperfield, Joseph D.; Telford, Richard J.

    2015-04-01

    Construction of accurate age-depth relationships and realistic assessment of their uncertainties is one of the fundamental prerequisites for comparing and correlating Late Quaternary stratigraphic proxy records. Four widely used age-depth modelling routines: i) clam, ii) OxCal, iii) Bacon, and iv) Bchron were tested using radiocarbon dates simulated from varved sediment stratigraphies. All methods produced average age-depth models that were close to the true varve age, but the uncertainty estimation differed considerably among models. Age uncertainties were underestimated by clam, whereas age uncertainties produced by Bchron were too large. Using OxCal and Bacon, setting of model specific parameters influenced the estimated uncertainties, which varied from too large to too small. Still, compared to the study by Telford et al. (2004), the use of Bayesian age-depth models greatly improved on the assessment of uncertainties of age-depth models. Reference: Telford et al. (2004), All age-depth models are wrong: but how badly? Quaternary Science Reviews, 23,1-5.

  3. Modeling the Information Age Combat Model: An Agent-Based Simulation of Network Centric Operations

    NASA Technical Reports Server (NTRS)

    Deller, Sean; Rabadi, Ghaith A.; Bell, Michael I.; Bowling, Shannon R.; Tolk, Andreas

    2010-01-01

    The Information Age Combat Model (IACM) was introduced by Cares in 2005 to contribute to the development of an understanding of the influence of connectivity on force effectiveness that can eventually lead to quantitative prediction and guidelines for design and employment. The structure of the IACM makes it clear that the Perron-Frobenius Eigenvalue is a quantifiable metric with which to measure the organization of a networked force. The results of recent experiments presented in Deller, et aI., (2009) indicate that the value of the Perron-Frobenius Eigenvalue is a significant measurement of the performance of an Information Age combat force. This was accomplished through the innovative use of an agent-based simulation to model the IACM and represents an initial contribution towards a new generation of combat models that are net-centric instead of using the current platform-centric approach. This paper describes the intent, challenges, design, and initial results of this agent-based simulation model.

  4. Age-Related Changes in Predictive Capacity Versus Internal Model Adaptability: Electrophysiological Evidence that Individual Differences Outweigh Effects of Age.

    PubMed

    Bornkessel-Schlesewsky, Ina; Philipp, Markus; Alday, Phillip M; Kretzschmar, Franziska; Grewe, Tanja; Gumpert, Maike; Schumacher, Petra B; Schlesewsky, Matthias

    2015-01-01

    Hierarchical predictive coding has been identified as a possible unifying principle of brain function, and recent work in cognitive neuroscience has examined how it may be affected by age-related changes. Using language comprehension as a test case, the present study aimed to dissociate age-related changes in prediction generation versus internal model adaptation following a prediction error. Event-related brain potentials (ERPs) were measured in a group of older adults (60-81 years; n = 40) as they read sentences of the form "The opposite of black is white/yellow/nice." Replicating previous work in young adults, results showed a target-related P300 for the expected antonym ("white"; an effect assumed to reflect a prediction match), and a graded N400 effect for the two incongruous conditions (i.e. a larger N400 amplitude for the incongruous continuation not related to the expected antonym, "nice," versus the incongruous associated condition, "yellow"). These effects were followed by a late positivity, again with a larger amplitude in the incongruous non-associated versus incongruous associated condition. Analyses using linear mixed-effects models showed that the target-related P300 effect and the N400 effect for the incongruous non-associated condition were both modulated by age, thus suggesting that age-related changes affect both prediction generation and model adaptation. However, effects of age were outweighed by the interindividual variability of ERP responses, as reflected in the high proportion of variance captured by the inclusion of by-condition random slopes for participants and items. We thus argue that - at both a neurophysiological and a functional level - the notion of general differences between language processing in young and older adults may only be of limited use, and that future research should seek to better understand the causes of interindividual variability in the ERP responses of older adults and its relation to cognitive performance. PMID

  5. The Statewide Training Model for a Continuing Education Certificate in Gerontology in Religion and Aging.

    ERIC Educational Resources Information Center

    Thompson, Barbara, Ed.; Payne, Barbara, Ed.

    This training model is a guide for developing statewide training for a continuing education certificate in gerontology in religion and aging. It is designed for use by gerontology educators, state office of aging executives, and leaders of religious judicatories. Section I begins with a description of the training model and covers where and how to…

  6. Glassy Transition and Aging in a Model Without Disorder

    NASA Astrophysics Data System (ADS)

    Franz, Silvio; Hertz, John

    1995-03-01

    We study the off-equilibrium relaxational dynamics of the Amit-Roginsky φ3 field theory, for which the mode coupling approximation is exact. We show that complex phenomena such as aging and ergodicity breaking are present at low temperature, similar to what is found in long range spin glasses. This is an example of how the mode coupling theory of the structural glass transition can be generalized to off-equilibrium situations.

  7. Muscle wasting in myotonic dystrophies: a model of premature aging

    PubMed Central

    Mateos-Aierdi, Alba Judith; Goicoechea, Maria; Aiastui, Ana; Fernández-Torrón, Roberto; Garcia-Puga, Mikel; Matheu, Ander; López de Munain, Adolfo

    2015-01-01

    Myotonic dystrophy type 1 (DM1 or Steinert’s disease) and type 2 (DM2) are multisystem disorders of genetic origin. Progressive muscular weakness, atrophy and myotonia are the most prominent neuromuscular features of these diseases, while other clinical manifestations such as cardiomyopathy, insulin resistance and cataracts are also common. From a clinical perspective, most DM symptoms are interpreted as a result of an accelerated aging (cataracts, muscular weakness and atrophy, cognitive decline, metabolic dysfunction, etc.), including an increased risk of developing tumors. From this point of view, DM1 could be described as a progeroid syndrome since a notable age-dependent dysfunction of all systems occurs. The underlying molecular disorder in DM1 consists of the existence of a pathological (CTG) triplet expansion in the 3′ untranslated region (UTR) of the Dystrophia Myotonica Protein Kinase (DMPK) gene, whereas (CCTG)n repeats in the first intron of the Cellular Nucleic acid Binding Protein/Zinc Finger Protein 9 (CNBP/ZNF9) gene cause DM2. The expansions are transcribed into (CUG)n and (CCUG)n-containing RNA, respectively, which form secondary structures and sequester RNA-binding proteins, such as the splicing factor muscleblind-like protein (MBNL), forming nuclear aggregates known as foci. Other splicing factors, such as CUGBP, are also disrupted, leading to a spliceopathy of a large number of downstream genes linked to the clinical features of these diseases. Skeletal muscle regeneration relies on muscle progenitor cells, known as satellite cells, which are activated after muscle damage, and which proliferate and differentiate to muscle cells, thus regenerating the damaged tissue. Satellite cell dysfunction seems to be a common feature of both age-dependent muscle degeneration (sarcopenia) and muscle wasting in DM and other muscle degenerative diseases. This review aims to describe the cellular, molecular and macrostructural processes involved in the

  8. Joint Bayesian analysis of birthweight and censored gestational age using finite mixture models

    PubMed Central

    Schwartz, Scott L.; Gelfand, Alan E.; Miranda, Marie L.

    2016-01-01

    Birthweight and gestational age are closely related and represent important indicators of a healthy pregnancy. Customary modeling for birthweight is conditional on gestational age. However, joint modeling directly addresses the relationship between gestational age and birthweight, and provides increased flexibility and interpretation as well as a strategy to avoid using gestational age as an intermediate variable. Previous proposals have utilized finite mixtures of bivariate regression models to incorporate well-established risk factors into analysis (e.g. sex and birth order of the baby, maternal age, race, and tobacco use) while examining the non-Gaussian shape of the joint birthweight and gestational age distribution. We build on this approach by demonstrating the inferential (prognostic) benefits of joint modeling (e.g. investigation of `age inappropriate' outcomes like small for gestational age) and hence re-emphasize the importance of capturing the non-Gaussian distributional shapes. We additionally extend current models through a latent specification which admits interval-censored gestational age. We work within a Bayesian framework which enables inference beyond customary parameter estimation and prediction as well as exact uncertainty assessment. The model is applied to a portion of the 2003–2006 North Carolina Detailed Birth Record data (n=336129) available through the Children's Environmental Health Initiative and is fitted using the Bayesian methodology and Markov chain Monte Carlo approaches. PMID:20575047

  9. Evaluation and clinical significance of the stomach age model for evaluating aging of the stomach-a multicenter study in China

    PubMed Central

    2014-01-01

    Background A higher prevalence of chronic atrophic gastritis (CAG) occurs in younger adults in Asia. We used Stomach Age to examine the different mechanisms of CAG between younger adults and elderly individuals, and established a simple model of cancer risk that can be applied to CAG surveillance. Methods Stomach Age was determined by FISH examination of telomere length in stomach biopsies. Δψm was also determined by flow cytometry. Sixty volunteers were used to confirm the linear relationship between telomere length and age while 120 subjects were used to build a mathematical model by a multivariate analysis. Overall, 146 subjects were used to evaluate the validity of the model, and 1,007 subjects were used to evaluate the relationship between prognosis and Δage (calculated from the mathematical model). ROC curves were used to evaluate the relationship between prognosis and Δage and to determine the cut-off point for Δage. Results We established that a tight linear relationship between the telomere length and the age. The telomere length was obvious different between patients with and without CAG even in the same age. Δψm decreased in individuals whose Stomach Age was greater than real age, especially in younger adults. A mathematical model of Stomach Age (real age + Δage) was successfully constructed which was easy to apply in clinical work. A higher Δage was correlated with a worse outcome. The criterion of Δage >3.11 should be considered as the cut-off to select the subgroup of patients who require endoscopic surveillance. Conclusion Variation in Stomach Age between individuals of the same biological age was confirmed. Attention should be paid to those with a greater Stomach Age, especially in younger adults. The Δage in the Simple Model can be used as a criterion to select CAG patients for gastric cancer surveillance. PMID:25057261

  10. Progressive Age-Related Changes Similar to Age-Related Macular Degeneration in a Transgenic Mouse Model

    PubMed Central

    Rakoczy, Piroska Elizabeth; Zhang, Dan; Robertson, Terry; Barnett, Nigel L.; Papadimitriou, John; Constable, Ian Jeffrey; Lai, Chooi-May

    2002-01-01

    Age-related macular degeneration (AMD) is the major cause of blindness in the developed world. Its pathomechanism is unknown and its late onset, complex genetics and strong environmental components have all hampered investigations. Here we demonstrate the development of an animal model for AMD that reproduces features associated with geographic atrophy; a transgenic mouse line (mcd/mcd) expressing a mutated form of cathepsin D that is enzymatically inactive thus impairing processing of phagocytosed photoreceptor outer segments in the retinal pigment epithelial (RPE) cells. Pigmentary changes indicating RPE cell atrophy and a decreased response to flash electroretinograms were observed in 11- to 12-month-old mcd/mcd mice. Histological studies showed RPE cell proliferation, photoreceptor degeneration, shortening of photoreceptor outer segments, and accumulation of immunoreactive photoreceptor breakdown products in the RPE cells. An accelerated photoreceptor cell death was detected in 12-month-old mcd/mcd mice. Transmission electron microscopy demonstrated presence of basal laminar and linear deposits that are considered to be the hallmarks of AMD. Small hard drusen associated with human age-related maculopathy were absent in the mcd/mcd mouse model at the ages analyzed. In summary, this model presents several features of AMD, thus providing a valuable tool for investigating the underlying biological processes and pathomechanism of AMD. PMID:12368224

  11. A statistical model including age to predict passenger postures in the rear seats of automobiles.

    PubMed

    Park, Jangwoon; Ebert, Sheila M; Reed, Matthew P; Hallman, Jason J

    2016-06-01

    Few statistical models of rear seat passenger posture have been published, and none has taken into account the effects of occupant age. This study developed new statistical models for predicting passenger postures in the rear seats of automobiles. Postures of 89 adults with a wide range of age and body size were measured in a laboratory mock-up in seven seat configurations. Posture-prediction models for female and male passengers were separately developed by stepwise regression using age, body dimensions, seat configurations and two-way interactions as potential predictors. Passenger posture was significantly associated with age and the effects of other two-way interaction variables depended on age. A set of posture-prediction models are presented for women and men, and the prediction results are compared with previously published models. This study is the first study of passenger posture to include a large cohort of older passengers and the first to report a significant effect of age for adults. The presented models can be used to position computational and physical human models for vehicle design and assessment. Practitioner Summary: The significant effects of age, body dimensions and seat configuration on rear seat passenger posture were identified. The models can be used to accurately position computational human models or crash test dummies for older passengers in known rear seat configurations. PMID:26328769

  12. Aging and strain softening model for episodic faulting

    USGS Publications Warehouse

    Stuart, W.D.

    1979-01-01

    Episodic slip on shallow crustal faults can be qualitatively explained by postulating a fault constitutive law that is the superposition of two limiting material responses: (1) strain softening after peak stress during large strain rates, and (2) strength (peak stress) recovery during aging at small strain rates. A single law permits a variety of seismic and aseismic phenomena to occur over a range of space and time scales. Specific cases are determined by the spatial variation of material constants, recent deformation history, crustal rigidity, and remote forcing. ?? 1979.

  13. Oxidative Damage in the Aging Heart: an Experimental Rat Model

    PubMed Central

    Marques, Gustavo Lenci; Neto, Francisco Filipak; Ribeiro, Ciro Alberto de Oliveira; Liebel, Samuel; de Fraga, Rogério; Bueno, Ronaldo da Rocha Loures

    2015-01-01

    Introduction: Several theories have been proposed to explain the cause of ‘aging’; however, the factors that affect this complex process are still poorly understood. Of these theories, the accumulation of oxidative damage over time is among the most accepted. Particularly, the heart is one of the most affected organs by oxidative stress. The current study, therefore, aimed to investigate oxidative stress markers in myocardial tissue of rats at different ages. Methods: Seventy-two rats were distributed into 6 groups of 12 animals each and maintained for 3, 6, 9, 12, 18 and 24 months. After euthanasia, the heart was removed and the levels of non-protein thiols, lipid peroxidation, and protein carbonylation, as well as superoxide dismutase and catalase activities were determined. Results: Superoxide dismutase, catalase activity and lipid peroxidation were reduced in the older groups of animals, when compared with the younger group. However, protein carbonylation showed an increase in the 12-month group followed by a decrease in the older groups. In addition, the levels of non-protein thiols were increased in the 12-month group and not detected in the older groups. Conclusion: Our data showed that oxidative stress is not associated with aging in the heart. However, an increase in non-protein thiols may be an important factor that compensates for the decrease of superoxide dismutase and catalase activity in the oldest rats, to maintain appropriate antioxidant defenses against oxidative insults. PMID:27006709

  14. Stochastic Process Model of Physiological Regeneration, Fertility and Aging

    NASA Astrophysics Data System (ADS)

    Akushevich, Igor; Manton, Kenneth

    2003-03-01

    A state space model of human birth, death processes is presented based upon a generalization of the Fokker-Planck-Kolmogorov (F-P-K) diffusion equation. In the model it is assumed that males and females are linked through the birth process and that birth and fetal growth, itself possibly described by a F-P-K equation, generates new probability mass in the population state space. Specific case of radiation as a risk factor is considered and analyzed. Life time generator is constructed on the basis of the developed model and its results are compared with existent physiological longitudinal data.

  15. Dynamical Masses of Young Stars. I. Discordant Model Ages of Upper Scorpius

    NASA Astrophysics Data System (ADS)

    Rizzuto, Aaron C.; Ireland, Michael J.; Dupuy, Trent J.; Kraus, Adam L.

    2016-02-01

    We present the results of a long-term orbit monitoring program, using sparse aperture masking observations taken with NIRC2 on the Keck-II telescope, of seven G- to M-type members of the Upper Scorpius subgroup of the Sco-Cen OB association. We present astrometry and derived orbital elements of the binary systems we have monitored, and also determine the age, component masses, distance, and reddening for each system using the orbital solutions and multi-band photometry, including Hubble Space Telescope photometry, and a Bayesian fitting procedure. We find that the models can be forced into agreement with any individual system by assuming an age, but that age is not consistent across the mass range of our sample. The G-type binary systems in our sample have model ages of ˜11.5 Myr, which is consistent with the latest age estimates for Upper Scorpius, while the M-type binary systems have significantly younger model ages of ˜7 Myr. Based on our fits, this age discrepancy in the models corresponds to a luminosity underprediction of 0.8-0.15 dex, or equivalently an effective temperature overprediction of 100-300 K for M-type stars at a given pre-main-sequence age. We also find that the M-type binary system RXJ 1550.0-2312 has an age (˜16 Myr) and distance (˜85 pc) consistent with membership in the Upper Centaurus Lupus subgroup.

  16. In vitro 3-D model based on extending time of culture for studying chronological epidermis aging.

    PubMed

    Dos Santos, Morgan; Metral, Elodie; Boher, Aurélie; Rousselle, Patricia; Thepot, Amélie; Damour, Odile

    2015-09-01

    Skin aging is a complex phenomenon in which several mechanisms operate simultaneously. Among them, intrinsic aging is a time-dependent process, which leads to gradual skin changes affecting its structure and function such as thinning down of both epidermal and dermal compartments and a flattening and fragility of the dermo-epidermal junction. Today, several approaches have been proposed for the generation of aged skin in vitro, including skin explants from aged donors and three-dimensional skin equivalent treated by aging-inducing chemical compounds or engineered with human cells isolated from aged donors. The aim of this study was to develop and validate a new in vitro model of aging based on skin equivalent demonstrating the same phenotypic changes that were observed in chronological aging. By using prolonged culture as a proxy for cellular aging, we extended to 120 days the culture time of a skin equivalent model based on collagen-glycosaminoglycan-chitosan porous polymer and engineered with human skin cells from photo-protected sites of young donors. Morphological, immunohistological and ultrastructural analysis at different time points of the culture allowed characterizing the phenotypic changes observed in our model in comparison to samples of non photo-exposed normal human skin from different ages. We firstly confirmed that long-term cultured skin equivalents are still morphologically consistent and functionally active even after 120 days of culture. However, similar to in vivo chronological skin aging a significant decrease of the epidermis thickness as well as the number of keratinocyte expressing proliferation marker Ki67 are observed in extended culture time skin equivalent. Epidermal differentiation markers loricrin, filaggrin, involucrin and transglutaminase, also strongly decreased. Ultrastructural analysis of basement membrane showed typical features of aged skin such as duplication of lamina densa and alterations of hemidesmosomes. Moreover, the

  17. Mathematical Model of Three Age-Structured Transmission Dynamics of Chikungunya Virus

    PubMed Central

    Agusto, Folashade B.; Easley, Shamise; Freeman, Kenneth; Thomas, Madison

    2016-01-01

    We developed a new age-structured deterministic model for the transmission dynamics of chikungunya virus. The model is analyzed to gain insights into the qualitative features of its associated equilibria. Some of the theoretical and epidemiological findings indicate that the stable disease-free equilibrium is globally asymptotically stable when the associated reproduction number is less than unity. Furthermore, the model undergoes, in the presence of disease induced mortality, the phenomenon of backward bifurcation, where the stable disease-free equilibrium of the model coexists with a stable endemic equilibrium when the associated reproduction number is less than unity. Further analysis of the model indicates that the qualitative dynamics of the model are not altered by the inclusion of age structure. This is further emphasized by the sensitivity analysis results, which shows that the dominant parameters of the model are not altered by the inclusion of age structure. However, the numerical simulations show the flaw of the exclusion of age in the transmission dynamics of chikungunya with regard to control implementations. The exclusion of age structure fails to show the age distribution needed for an effective age based control strategy, leading to a one size fits all blanket control for the entire population. PMID:27190548

  18. Molecular mechanisms and in vivo mouse models of skin aging associated with dermal matrix alterations.

    PubMed

    Hwang, Kyung-A; Yi, Bo-Rim; Choi, Kyung-Chul

    2011-03-01

    Skin is the most superficial body organ and plays an important role in protecting the body from environmental damage and in forming social relations. With the increase of the aging population in our society, dermatological and cosmetic concerns of skin aging are rapidly increasing. Skin aging is a complex process combined with intrinsic and extrinsic factors. Intrinsic or chronological skin aging results from the passage of time and is influenced by genetic factors. Extrinsic skin aging is mainly determined by UV irradiation, also called photoaging. These two types of aging processes are superimposed on sun-exposed skin, and have a common feature of causing dermal matrix alterations that mostly contribute to the formation of wrinkles, laxity, and fragility of aged skin. The dermal matrix contains extracellular matrix proteins such as collagen, elastin, and proteoglycans that confer the strength and resiliency of skin. Skin aging associated with dermal matrix alterations and atrophy can be caused by cellular senescence of dermal cells like fibroblasts, and decreased synthesis and accelerated degradation of dermal matrix components, especially collagen fibers. Both intrinsic aging and photoaging exert influence during each step of dermal matrix alteration via different mechanisms. Mouse models of skin aging have been extensively developed to elucidate intrinsic aging and photoaging processes, to validate in vitro biochemical data, and to test the effects of pharmacological tools for retarding skin aging because they have the advantages of being genetically similar to humans and are easily available. PMID:21826153

  19. GPU-Accelerated Molecular Modeling Coming Of Age

    PubMed Central

    Stone, John E.; Hardy, David J.; Ufimtsev, Ivan S.

    2010-01-01

    Graphics processing units (GPUs) have traditionally been used in molecular modeling solely for visualization of molecular structures and animation of trajectories resulting from molecular dynamics simulations. Modern GPUs have evolved into fully programmable, massively parallel co-processors that can now be exploited to accelerate many scientific computations, typically providing about one order of magnitude speedup over CPU code and in special cases providing speedups of two orders of magnitude. This paper surveys the development of molecular modeling algorithms that leverage GPU computing, the advances already made and remaining issues to be resolved, and the continuing evolution of GPU technology that promises to become even more useful to molecular modeling. Hardware acceleration with commodity GPUs is expected to benefit the overall computational biology community by bringing teraflops performance to desktop workstations and in some cases potentially changing what were formerly batch-mode computational jobs into interactive tasks. PMID:20675161

  20. Aging and Interdependence: A Theoretical Model for Close Relationships.

    ERIC Educational Resources Information Center

    Blieszner, Rosemary

    This paper demonstrates the utility of interdependence theory for understanding older persons' social relationships. Using friendship as an exemplary case, a model of expectations for and reactions to social exchanges is described. Exchanges which are perceived to be motivated by obligation are distinguished from those which are perceived to…

  1. A Comparison of the Age-Spectra from Data Assimilation Models

    NASA Technical Reports Server (NTRS)

    Schoeberl, Mark R.; Douglass, Anne R.; Zhu, Zheng-Xin; Pawson, Steven; Einaudi, Franco (Technical Monitor)

    2002-01-01

    We use kinematic and diabatic back trajectory calculations, driven by winds from a general circulation model (GCM) and two different data assimilation systems (DAS), to compute the age spectrum at three latitudes in the lower stratosphere. The age-spectra are compared to chemical transport model (CTM) calculations, and the mean ages from all of these studies are compared to observations. The age spectra computed using the GCM winds show a reasonably well-isolated tropics in good agreement with observations; however, the age spectra determined from the DAS differ from the GCM spectra. For the diabatic trajectory calculations, the age spectrum is too broad as a result of too much exchange between the tropics and mid-latitudes. The age spectrum determined using the kinematic trajectory calculation is less broad and lacks an age offset; both of these features are due to excessive vertical dispersion of parcels. The tropical and mid-latitude mean age difference between the diabatically and kinematically determined age-spectra is about one year, the former being older. The CTM calculation of the age spectrum using the DAS winds shows the same dispersive characteristics of the kinematic trajectory calculation. These results suggest that the current DAS products will not give realistic trace gas distributions for long integrations; they also help explain why the mean ages determined in a number of previous DAS driven CTM's are too young compared with observations. Finally, we note trajectory-generated age spectra show significant age anomalies correlated with the seasonal cycles, and these anomalies can be linked to year-to-year variations in the tropical heating rate. These anomalies are suppressed in the CTM spectra suggesting that the CTM transport is too diffusive.

  2. In vivo animal models of body composition in aging

    SciTech Connect

    Yasumura, S. |; Jones, K.; Spanne, P.; Schidlovsky, G.; Wielopolski, L.; Ren, X.; Glaros, D.; Xatzikonstantinou, Y. |

    1992-12-31

    We developed several techniques that provide data on body elemental composition from in vivo measurements in rats. These methods include total body potassium by whole-body counting of endogenous {sup 40}K; total body calcium (TBCa), sodium and chloride by in vivo neutron activation analysis and total body phosphorus (TBP) and nitrogen (TBN) by photon activation analysis. These elements provide information on total body fat, total body protein and skeletal mass. Measurements were made in 6-, 12- and 24-month-old rats. TBN Increased slightly between 6 and 12 months but was significantly lower by 24 months, indicating a substantial loss in total body protein. Working at the National Synchrotron light Source, we studied rat femurs by computed microtomography (CMT), and the elemental profile of the femur cortex by synchrotron-radiation induced X-ray emission (SRIXE). Although there were no significant changes in TBCA and TBP, indices of skeletal mass, CMT revealed a marked increase in the size and number of cavities in the endosteal region of the femur cortex with increasing age. The SRIXE analysis of this cortical bone revealed a parallel decrease in the endosteal Ca/P ratio. Thus, there are major alterations in bone morphology and regional elemental composition despite only modest changes in total skeletal mass.

  3. Dynamical network model for age-related health deficits and mortality

    NASA Astrophysics Data System (ADS)

    Taneja, Swadhin; Mitnitski, Arnold B.; Rockwood, Kenneth; Rutenberg, Andrew D.

    2016-02-01

    How long people live depends on their health, and how it changes with age. Individual health can be tracked by the accumulation of age-related health deficits. The fraction of age-related deficits is a simple quantitative measure of human aging. This quantitative frailty index (F ) is as good as chronological age in predicting mortality. In this paper, we use a dynamical network model of deficits to explore the effects of interactions between deficits, deficit damage and repair processes, and the connection between the F and mortality. With our model, we qualitatively reproduce Gompertz's law of increasing human mortality with age, the broadening of the F distribution with age, the characteristic nonlinear increase of the F with age, and the increased mortality of high-frailty individuals. No explicit time-dependence in damage or repair rates is needed in our model. Instead, implicit time-dependence arises through deficit interactions—so that the average deficit damage rates increase, and deficit repair rates decrease, with age. We use a simple mortality criterion, where mortality occurs when the most connected node is damaged.

  4. Comparative and alternative approaches and novel animal models for aging research

    PubMed Central

    Kristan, D. M.

    2008-01-01

    This special issue of AGE showcases powerful alternative or unconventional approaches to basic aging research, including the use of exceptionally long-lived animal model species and comparative methods from evolutionary biology. In this opening paper, we introduce several of these alternative aging research themes, including the comparative phylogenetic approach. This approach applies modern inferential methods for dissecting basic physiological and biochemical mechanisms correlated with phenotypic traits including longevity, slow aging, sustained somatic maintenance, and repair of molecular damage. Comparative methods can be used to assess the general relevance of specific aging mechanisms—including oxidative processes—to diverse animal species, as well as to assess their potential clinical relevance to humans and other mammals. We also introduce several other novel, underexploited approaches with particular relevance to biogerontology, including the use of model animal species or strains that retain natural genetic heterogeneity, studies of effects of infectious disease and parasites on aging and responses to caloric restriction, studies of reproductive aging, and naturally occurring sex differences in aging. We emphasize the importance of drawing inferences from aging phenomena in laboratory studies that can be applied to clinically relevant aging syndromes in long-lived, outbred animals, including humans. PMID:19424857

  5. Aging Well and the Environment: Toward an Integrative Model and Research Agenda for the Future

    ERIC Educational Resources Information Center

    Wahl, Hans-Werner; Iwarsson, Susanne; Oswald, Frank

    2012-01-01

    Purpose of the Study: The effects of the physical-spatial-technical environment on aging well have been overlooked both conceptually and empirically. In the spirit of M. Powell Lawton's seminal work on aging and environment, this article attempts to rectify this situation by suggesting a new model of how older people interact with their…

  6. Age Differences within Secular IQ Trends: An Individual Growth Modeling Approach

    ERIC Educational Resources Information Center

    Kanaya, Tomoe; Ceci, Stephen J.; Scullin, Matthew H.

    2005-01-01

    Age differences within the yo-yo trend in IQ, caused when aging norms that produce inflated scores are replaced with new norms, were examined using longitudinal WISC, WISC-R and WISC-III records of students tested for special education services from 10 school districts. Descriptive and individual growth modeling analyses revealed that while the…

  7. A Model for Incorporating Content on Aging into the Curriculum: K-12.

    ERIC Educational Resources Information Center

    Blackwell, David L.; Hunt, Sara Stockard

    Following a statement of the problem of putting aging education in the elementary secondary curriculum, and a review of the relevant literature, a model for developing a curriculum on aging is presented. An overview of the 3-year project, developed in Baton Rouge, Louisiana schools for grades K-12, is offered, including activities and yearly…

  8. Modeling the Phenotypic Architecture of Autism Symptoms from Time of Diagnosis to Age 6

    ERIC Educational Resources Information Center

    Georgiades, Stelios; Boyle, Michael; Szatmari, Peter; Hanna, Steven; Duku, Eric; Zwaigenbaum, Lonnie; Bryson, Susan; Fombonne, Eric; Volden, Joanne; Mirenda, Pat; Smith, Isabel; Roberts, Wendy; Vaillancourt, Tracy; Waddell, Charlotte; Bennett, Teresa; Elsabbagh, Mayada; Thompson, Ann

    2014-01-01

    The latent class structure of autism symptoms from the time of diagnosis to age 6 years was examined in a sample of 280 children with autism spectrum disorder. Factor mixture modeling was performed on 26 algorithm items from the Autism Diagnostic Interview-Revised at diagnosis (Time 1) and again at age 6 (Time 2). At Time 1, a…

  9. Adaptive Behavior and Cognitive Function of Adults with Down Syndrome: Modeling Change with Age.

    ERIC Educational Resources Information Center

    Hawkins, Barbara A.; Eklund, Susan J.; James, David R.; Foose, Alice K.

    2003-01-01

    Fifty-eight adults with Down syndrome were assessed longitudinally over 10 years for the purpose of modeling aging-related change in cognitive function and adaptive behavior. Findings provide further evidence of changes in performance with age and include selected effects for participants who completed the study and those lost to follow-up.…

  10. Conscientiousness, health, and aging: the life course of personality model.

    PubMed

    Shanahan, Michael J; Hill, Patrick L; Roberts, Brent W; Eccles, Jacquelynne; Friedman, Howard S

    2014-05-01

    The Conscientiousness (C) of the self and significant others influences health by way of mediational chains involving socioeconomic attainment, the avoidance and neutralization of stressors, the promotion of health behaviors and the minimization of risk behaviors, and the management of symptoms and diseases. Yet, meta-analyses reveal that these associations are moderated by factors that are not well understood. We propose the Life Course of Personality Model (LCP Model), which comprises a series of hypotheses that suggest how such mediational chains are subject to 2 sources of contingency. First, the mechanisms by which C translates into health and the avoidance of risk change from early childhood to late adulthood, involving processes that are specific to phases of the life course; also, however, C influences health by way of continuous processes extending over many decades of life. Second, C may be more consequential in some social contexts than in others, and when accompanied by some constellations of personality characteristics than by others. That is, the mediational processes by which C translates into health and the avoidance of disease are likely moderated by timing, social context (including the C of others), and other aspects of the individual's personality. We consider methodological implications of the LCP Model. PMID:23244406

  11. Modeling old-age wealth with endogenous early-life outcomes: The case of Mexico

    PubMed Central

    DeGraff, Deborah S.; Wong, Rebeca

    2014-01-01

    This paper contributes to the literature on the life course and aging by examining the association between early-life outcomes and late-life well being, using data from the Mexican Health and Aging Study. Empirical research in this area has been challenged by the potential endogeneity of the early-life outcomes of interest, an issue which most studies ignore or downplay. Our contribution takes two forms: (1) we examine in detail the potential importance of two key life-cycle outcomes, age at marriage (a measure of family formation) and years of educational attainment (a measure of human capital investment) for old-age wealth, and (2) we illustrate the empirical value of past context variables that could help model the association between early-life outcomes and late-life well being. Our illustrative approach, matching macro-level historical policy and census variables to individual records to use as instruments in modeling the endogeneity of early-life behaviors, yields a statistically identified two-stage model of old-age wealth with minimum bias. We use simulations to show that the results for the model of wealth in old age are meaningfully different when comparing the approach that accounts for endogeneity with an approach that assumes exogeneity of early-life outcomes. Furthermore, our results suggest that in the Mexican case, models which ignore the potential endogeneity of early-life outcomes are likely to under-estimate the effects of such variables on old-age wealth. PMID:25170434

  12. Modeling old-age wealth with endogenous early-life outcomes: The case of Mexico.

    PubMed

    DeGraff, Deborah S; Wong, Rebeca

    2014-04-01

    This paper contributes to the literature on the life course and aging by examining the association between early-life outcomes and late-life well being, using data from the Mexican Health and Aging Study. Empirical research in this area has been challenged by the potential endogeneity of the early-life outcomes of interest, an issue which most studies ignore or downplay. Our contribution takes two forms: (1) we examine in detail the potential importance of two key life-cycle outcomes, age at marriage (a measure of family formation) and years of educational attainment (a measure of human capital investment) for old-age wealth, and (2) we illustrate the empirical value of past context variables that could help model the association between early-life outcomes and late-life well being. Our illustrative approach, matching macro-level historical policy and census variables to individual records to use as instruments in modeling the endogeneity of early-life behaviors, yields a statistically identified two-stage model of old-age wealth with minimum bias. We use simulations to show that the results for the model of wealth in old age are meaningfully different when comparing the approach that accounts for endogeneity with an approach that assumes exogeneity of early-life outcomes. Furthermore, our results suggest that in the Mexican case, models which ignore the potential endogeneity of early-life outcomes are likely to under-estimate the effects of such variables on old-age wealth. PMID:25170434

  13. Mathematical modeling of left ventricular dimensional changes in mice during aging

    PubMed Central

    2012-01-01

    Cardiac aging is characterized by diastolic dysfunction of the left ventricle (LV), which is due in part to increased LV wall stiffness. In the diastolic phase, myocytes are relaxed and extracellular matrix (ECM) is a critical determinant to the changes of LV wall stiffness. To evaluate the effects of ECM composition on cardiac aging, we developed a mathematical model to predict LV dimension and wall stiffness changes in aging mice by integrating mechanical laws and our experimental results. We measured LV dimension, wall thickness, LV mass, and collagen content for wild type (WT) C57/BL6J mice of ages ranging from 7.3 months to those of 34.0 months. The model was established using the thick wall theory and stretch-induced tissue growth to an isotropic and homogeneous elastic composite with mixed constituents. The initial conditions of the simulation were set based on the data from the young mice. Matlab simulations of this mathematical model demonstrated that the model captured the major features of LV remodeling with age and closely approximated experimental results. Specifically, the temporal progression of the LV interior and exterior dimensions demonstrated the same trend and order-of-magnitude change as our experimental results. In conclusion, we present here a validated mathematical model of cardiac aging that applies the thick-wall theory and stretch-induced tissue growth to LV remodeling with age. PMID:23281647

  14. Mathematical modeling of left ventricular dimensional changes in mice during aging.

    PubMed

    Yang, Tianyi; Chiao, Ying Ann; Wang, Yunji; Voorhees, Andrew; Han, Hai-Chao; Lindsey, Merry L; Jin, Yu-Fang

    2012-01-01

    Cardiac aging is characterized by diastolic dysfunction of the left ventricle (LV), which is due in part to increased LV wall stiffness. In the diastolic phase, myocytes are relaxed and extracellular matrix (ECM) is a critical determinant to the changes of LV wall stiffness. To evaluate the effects of ECM composition on cardiac aging, we developed a mathematical model to predict LV dimension and wall stiffness changes in aging mice by integrating mechanical laws and our experimental results. We measured LV dimension, wall thickness, LV mass, and collagen content for wild type (WT) C57/BL6J mice of ages ranging from 7.3 months to those of 34.0 months. The model was established using the thick wall theory and stretch-induced tissue growth to an isotropic and homogeneous elastic composite with mixed constituents. The initial conditions of the simulation were set based on the data from the young mice. Matlab simulations of this mathematical model demonstrated that the model captured the major features of LV remodeling with age and closely approximated experimental results. Specifically, the temporal progression of the LV interior and exterior dimensions demonstrated the same trend and order-of-magnitude change as our experimental results. In conclusion, we present here a validated mathematical model of cardiac aging that applies the thick-wall theory and stretch-induced tissue growth to LV remodeling with age. PMID:23281647

  15. A novel strategy for forensic age prediction by DNA methylation and support vector regression model

    PubMed Central

    Xu, Cheng; Qu, Hongzhu; Wang, Guangyu; Xie, Bingbing; Shi, Yi; Yang, Yaran; Zhao, Zhao; Hu, Lan; Fang, Xiangdong; Yan, Jiangwei; Feng, Lei

    2015-01-01

    High deviations resulting from prediction model, gender and population difference have limited age estimation application of DNA methylation markers. Here we identified 2,957 novel age-associated DNA methylation sites (P < 0.01 and R2 > 0.5) in blood of eight pairs of Chinese Han female monozygotic twins. Among them, nine novel sites (false discovery rate < 0.01), along with three other reported sites, were further validated in 49 unrelated female volunteers with ages of 20–80 years by Sequenom Massarray. A total of 95 CpGs were covered in the PCR products and 11 of them were built the age prediction models. After comparing four different models including, multivariate linear regression, multivariate nonlinear regression, back propagation neural network and support vector regression, SVR was identified as the most robust model with the least mean absolute deviation from real chronological age (2.8 years) and an average accuracy of 4.7 years predicted by only six loci from the 11 loci, as well as an less cross-validated error compared with linear regression model. Our novel strategy provides an accurate measurement that is highly useful in estimating the individual age in forensic practice as well as in tracking the aging process in other related applications. PMID:26635134

  16. Dynamical properties of the Penna aging model applied to the population of wolves

    NASA Astrophysics Data System (ADS)

    Makowiec, Danuta

    1997-02-01

    The parameters of th Penna bit-string model of aging of biological systems are systematically tested to better understand the model itself as well as the results arising from applying this model to studies of the development of the stationary population of Alaska wolves.

  17. Age-dependent cognitive impairment in a Drosophila Fragile X model and its pharmacological rescue

    PubMed Central

    Choi, Catherine H.; Schoenfeld, Brian P.; Liebelt, David A.; Ferreiro, David; Ferrick, Neal J.; Hinchey, Paul; Kollaros, Maria; Rudominer, Rebecca L.; Terlizzi, Allison M.; Koenigsberg, Eric; Wang, Yan; Sumida, Ai; Nguyen, Hanh T.; Bell, Aaron J.; McDonald, Thomas V.

    2010-01-01

    Fragile X syndrome afflicts 1 in 2,500 individuals and is the leading heritable cause of mental retardation worldwide. The overriding clinical manifestation of this disease is mild to severe cognitive impairment. Age-dependent cognitive decline has been identified in Fragile X patients, although it has not been fully characterized nor examined in animal models. A Drosophila model of this disease has been shown to display phenotypes bearing similarity to Fragile X symptoms. Most notably, we previously identified naive courtship and memory deficits in young adults with this model that appear to be due to enhanced metabotropic glutamate receptor (mGluR) signaling. Herein we have examined age-related cognitive decline in the Drosophila Fragile X model and found an age-dependent loss of learning during training. We demonstrate that treatment with mGluR antagonists or lithium can prevent this age-dependent cognitive impairment. We also show that treatment with mGluR antagonists or lithium during development alone displays differential efficacy in its ability to rescue naive courtship, learning during training and memory in aged flies. Furthermore, we show that continuous treatment during aging effectively rescues all of these phenotypes. These results indicate that the Drosophila model recapitulates the age-dependent cognitive decline observed in humans. This places Fragile X in a category with several other diseases that result in age-dependent cognitive decline. This demonstrates a role for the Drosophila Fragile X Mental Retardation Protein (dFMR1) in neuronal physiology with regard to cognition during the aging process. Our results indicate that misregulation of mGluR activity may be causative of this age onset decline and strengthens the possibility that mGluR antagonists and lithium may be potential pharmacologic compounds for counteracting several Fragile X symptoms. PMID:20039205

  18. Degeneration of the Y chromosome in evolutionary aging models

    NASA Astrophysics Data System (ADS)

    Lobo, M. P.; Onody, R. N.

    2005-06-01

    The Y chromosomes are genetically degenerated and do not recombine with their matching partners X. Recombination of XX pairs is pointed out as the key factor for the Y chromosome degeneration. However, there is an additional evolutionary force driving sex-chromosomes evolution. Here we show this mechanism by means of two different evolutionary models, in which sex chromosomes with non-recombining XX and XY pairs of chromosomes is considered. Our results show three curious effects. First, we observed that even when both XX and XY pairs of chromosomes do not recombine, the Y chromosomes still degenerate. Second, the accumulation of mutations on Y chromosomes followed a completely different pattern then those accumulated on X chromosomes. And third, the models may differ with respect to sexual proportion. These findings suggest that a more primeval mechanism rules the evolution of Y chromosomes due exclusively to the sex-chromosomes asymmetry itself, i.e., the fact that Y chromosomes never experience female bodies. Over aeons, natural selection favored X chromosomes spontaneously, even if at the very beginning of evolution, both XX and XY pairs of chromosomes did not recombine.

  19. Age-Related Changes in Predictive Capacity Versus Internal Model Adaptability: Electrophysiological Evidence that Individual Differences Outweigh Effects of Age

    PubMed Central

    Bornkessel-Schlesewsky, Ina; Philipp, Markus; Alday, Phillip M.; Kretzschmar, Franziska; Grewe, Tanja; Gumpert, Maike; Schumacher, Petra B.; Schlesewsky, Matthias

    2015-01-01

    Hierarchical predictive coding has been identified as a possible unifying principle of brain function, and recent work in cognitive neuroscience has examined how it may be affected by age–related changes. Using language comprehension as a test case, the present study aimed to dissociate age-related changes in prediction generation versus internal model adaptation following a prediction error. Event-related brain potentials (ERPs) were measured in a group of older adults (60–81 years; n = 40) as they read sentences of the form “The opposite of black is white/yellow/nice.” Replicating previous work in young adults, results showed a target-related P300 for the expected antonym (“white”; an effect assumed to reflect a prediction match), and a graded N400 effect for the two incongruous conditions (i.e. a larger N400 amplitude for the incongruous continuation not related to the expected antonym, “nice,” versus the incongruous associated condition, “yellow”). These effects were followed by a late positivity, again with a larger amplitude in the incongruous non-associated versus incongruous associated condition. Analyses using linear mixed-effects models showed that the target-related P300 effect and the N400 effect for the incongruous non-associated condition were both modulated by age, thus suggesting that age-related changes affect both prediction generation and model adaptation. However, effects of age were outweighed by the interindividual variability of ERP responses, as reflected in the high proportion of variance captured by the inclusion of by-condition random slopes for participants and items. We thus argue that – at both a neurophysiological and a functional level – the notion of general differences between language processing in young and older adults may only be of limited use, and that future research should seek to better understand the causes of interindividual variability in the ERP responses of older adults and its relation to

  20. Oxidative stress and age-related changes in T cells: is thalassemia a model of accelerated immune system aging?

    PubMed Central

    Ghatreh-Samani, Mahdi; Esmaeili, Nafiseh; Soleimani, Masoud; Asadi-Samani, Majid; Ghatreh-Samani, Keihan

    2016-01-01

    Iron overload in β-thalassemia major occurs mainly due to blood transfusion, an essential treatment for β-thalassemia major patients, which results in oxidative stress. It has been thought that oxidative stress causes elevation of immune system senescent cells. Under this condition, cells normally enhance in aging, which is referred to as premature immunosenescence. Because there is no animal model for immunosenescence, most knowledge on the immunosenescence pattern is based on induction of immunosenescence. In this review, we describe iron overload and oxidative stress in β-thalassemia major patients and how they make these patients a suitable human model for immunosenescence. We also consider oxidative stress in some kinds of chronic virus infections, which induce changes in the immune system similar to β-thalassemia major. In conclusion, a therapeutic approach used to improve the immune system in such chronic virus diseases, may change the immunosenescence state and make life conditions better for β-thalassemia major patients. PMID:27095931

  1. The zebrafish as a gerontology model in nervous system aging, disease, and repair.

    PubMed

    Van Houcke, Jessie; De Groef, Lies; Dekeyster, Eline; Moons, Lieve

    2015-11-01

    Considering the increasing number of elderly in the world's population today, developing effective treatments for age-related pathologies is one of the biggest challenges in modern medical research. Age-related neurodegeneration, in particular, significantly impacts important sensory, motor, and cognitive functions, seriously constraining life quality of many patients. Although our understanding of the causal mechanisms of aging has greatly improved in recent years, animal model systems still have much to tell us about this complex process. Zebrafish (Danio rerio) have gained enormous popularity for this research topic over the past decade, since their life span is relatively short but, like humans, they are still subject to gradual aging. In addition, the extensive characterization of its well-conserved molecular and cellular physiology makes the zebrafish an excellent model to unravel the underlying mechanisms of aging, disease, and repair. This review provides a comprehensive overview of the progress made in zebrafish gerontology, with special emphasis on nervous system aging. We review the evidence that classic hallmarks of aging can also be recognized within this small vertebrate, both at the molecular and cellular level. Moreover, we illustrate the high level of similarity with age-associated human pathologies through a survey of the functional deficits that arise as zebrafish age. PMID:26538520

  2. Understanding the link between sexual selection, sexual conflict and aging using crickets as a model.

    PubMed

    Archer, C Ruth; Hunt, John

    2015-11-01

    Aging evolved because the strength of natural selection declines over the lifetime of most organisms. Weak natural selection late in life allows the accumulation of deleterious mutations and may favor alleles that have positive effects on fitness early in life, but costly pleiotropic effects expressed later on. While this decline in natural selection is central to longstanding evolutionary explanations for aging, a role for sexual selection and sexual conflict in the evolution of lifespan and aging has only been identified recently. Testing how sexual selection and sexual conflict affect lifespan and aging is challenging as it requires quantifying male age-dependent reproductive success. This is difficult in the invertebrate model organisms traditionally used in aging research. Research using crickets (Orthoptera: Gryllidae), where reproductive investment can be easily measured in both sexes, has offered exciting and novel insights into how sexual selection and sexual conflict affect the evolution of aging, both in the laboratory and in the wild. Here we discuss how sexual selection and sexual conflict can be integrated alongside evolutionary and mechanistic theories of aging using crickets as a model. We then highlight the potential for research using crickets to further advance our understanding of lifespan and aging. PMID:26150061

  3. Systems integrity in health and aging - an animal model approach

    PubMed Central

    2013-01-01

    Human lifespan is positively correlated with childhood intelligence, as measured by psychometric (IQ) tests. The strength of this correlation is similar to the negative effect that smoking has on the life course. This result suggests that people who perform well on psychometric tests in childhood may remain healthier and live longer. The correlation, however, is debated: is it caused exclusively by social-environmental factors or could it also have a biological component? Biological traits of systems integrity that might result in correlations between brain function and lifespan have been suggested but are not well-established, and it is questioned what useful knowledge can come from understanding such mechanisms. In a recent study, we found a positive correlation between brain function and longevity in honey bees. Honey bees are highly social, but relevant social-environmental factors that contribute to cognition-survival correlations in humans are largely absent from insect colonies. Our results, therefore, suggest a biological explanation for the correlation in the bee. Here, we argue that individual differences in stress handling (coping) mechanisms, which both affect the bees’ performance in tests of brain function and their survival could be a trait of systems integrity. Individual differences in coping are much studied in vertebrates, and several species provide attractive models. Here, we discuss how pigs are an interesting model for studying behavioural, physiological and molecular mechanisms that are recruited during stress and that can drive correlations between health, cognition and longevity traits. By revealing biological factors that make individuals susceptible to stress, it might be possible to alleviate health and longevity disparities in people. PMID:24472488

  4. Dune Morphometry in the Age of Digital Elevation Models

    NASA Astrophysics Data System (ADS)

    Lancaster, N.

    2014-12-01

    Dune patterns can be characterized in many different ways. Relationships between dune height, width and spacing, and the spatial variation in these parameters have been widely employed to provide quantitative information that can be used to describe dune patterns and make comparisons between dunes in widely separated areas, as well as to identify different generations of dunes. Digital elevation models (e.g. ASTER GDEM) provide a rich resource of data for analyses of dune patterns at landscape scales in several ways, including: (1) more extensive analyses using traditional measures, such as relationships between dune height and spacing, and the spatial variation in these parameters; and (2) estimation of sediment thickness on a regional scale. Analyses of data for Arabian and Namibian sand seas and dune fields show that dune height and spacing relationships are much more variable than previously reported and call into question existing models. Regional patterns of sediment thickness reveal areas of erosion, bypass, and accumulation that can be related to transport pathways and wind regimes. The widespread occurrence of complex dune patterns as well as the magnitude of the newly available data sets however requires more sophisticated analyses than simple extraction of dune morphometric parameters using GIS approaches. Geostatistical analyses using spatial autocorrelation, Fourier, and Wavelet methods have been employed in analyses of sub-aqueous bedforms and show promise for dune systems. Automated or semi-automated identification of dune length, width, spacing, and trends using advanced image analysis techniques such as linear segment detection is a potentially transformative approach. The strengths and weaknesses of these methods to provide pertinent geomorphic information are currently being evaluated, but they have the potential to provide new insights into the nature of dune patterns.

  5. Systems integrity in health and aging - an animal model approach.

    PubMed

    Oostindjer, Marije; Amdam, Gro V

    2013-01-01

    Human lifespan is positively correlated with childhood intelligence, as measured by psychometric (IQ) tests. The strength of this correlation is similar to the negative effect that smoking has on the life course. This result suggests that people who perform well on psychometric tests in childhood may remain healthier and live longer. The correlation, however, is debated: is it caused exclusively by social-environmental factors or could it also have a biological component? Biological traits of systems integrity that might result in correlations between brain function and lifespan have been suggested but are not well-established, and it is questioned what useful knowledge can come from understanding such mechanisms. In a recent study, we found a positive correlation between brain function and longevity in honey bees. Honey bees are highly social, but relevant social-environmental factors that contribute to cognition-survival correlations in humans are largely absent from insect colonies. Our results, therefore, suggest a biological explanation for the correlation in the bee. Here, we argue that individual differences in stress handling (coping) mechanisms, which both affect the bees' performance in tests of brain function and their survival could be a trait of systems integrity. Individual differences in coping are much studied in vertebrates, and several species provide attractive models. Here, we discuss how pigs are an interesting model for studying behavioural, physiological and molecular mechanisms that are recruited during stress and that can drive correlations between health, cognition and longevity traits. By revealing biological factors that make individuals susceptible to stress, it might be possible to alleviate health and longevity disparities in people. PMID:24472488

  6. Grape powder treatment prevents anxiety-like behavior in a rat model of aging.

    PubMed

    Patki, Gaurav; Ali, Quaisar; Pokkunuri, Indira; Asghar, Mohammad; Salim, Samina

    2015-06-01

    Earlier, we have reported that grape powder (GP) treatment prevented pharmacologic and psychological stress-induced anxiety-like behavior and memory impairment in rats. Protective effects of GP were attributed to its antioxidant effects. In this study, we tested the hypothesis that age-associated behavioral and cognitive deficits such as anxiety and memory impairment will be ameliorated with GP treatment. Using a National Institute of Aging recommended rodent model of aging, we examined a potentially protective role of antioxidant-rich GP in age-associated anxiety-like behavior and memory impairment. Male Fischer 344 rats were randomly assigned into 4 groups: young rats (3 months old) provided with tap water or with 15 g/L GP dissolved in tap water for 3 weeks, aged rats (21 months old) provided with tap water or with GP-treated tap water for 3 weeks (AG-GP). Anxiety-like behavior was significantly greater in aged rats compared with young rats, GP-treated young rats, or aged control rats (P < .05). Also, GP treatment prevented age-induced anxiety-like behavior in AG-GP rats (P < .05). Neither short-term nor long-term age-associated memory deficits improved with GP treatment in AG-GP rats. Furthermore, aged rats showed increased level of physiological stress (corticosterone) and increased oxidative stress in the plasma (8-isoprostane) as well as in selected brain areas (protein carbonylation). Grape powder treatment prevented age-induced increase in corticosterone levels and plasma 8-isoprostane levels in aged rats (P < .05), whereas protein carbonylation was recovered in the amygdala region only (P < .05). Grape powder by regulating oxidative stress ameliorates age-induced anxiety-like behavior in rats, whereas age-associated memory deficits seem unaffected with GP treatment. PMID:26022140

  7. Human iPSC-based modeling of late-onset disease via progerin-induced aging.

    PubMed

    Miller, Justine D; Ganat, Yosif M; Kishinevsky, Sarah; Bowman, Robert L; Liu, Becky; Tu, Edmund Y; Mandal, Pankaj K; Vera, Elsa; Shim, Jae-won; Kriks, Sonja; Taldone, Tony; Fusaki, Noemi; Tomishima, Mark J; Krainc, Dimitri; Milner, Teresa A; Rossi, Derrick J; Studer, Lorenz

    2013-12-01

    Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) resets their identity back to an embryonic age and, thus, presents a significant hurdle for modeling late-onset disorders. In this study, we describe a strategy for inducing aging-related features in human iPSC-derived lineages and apply it to the modeling of Parkinson's disease (PD). Our approach involves expression of progerin, a truncated form of lamin A associated with premature aging. We found that expression of progerin in iPSC-derived fibroblasts and neurons induces multiple aging-related markers and characteristics, including dopamine-specific phenotypes such as neuromelanin accumulation. Induced aging in PD iPSC-derived dopamine neurons revealed disease phenotypes that require both aging and genetic susceptibility, such as pronounced dendrite degeneration, progressive loss of tyrosine hydroxylase (TH) expression, and enlarged mitochondria or Lewy-body-precursor inclusions. Thus, our study suggests that progerin-induced aging can be used to reveal late-onset age-related disease features in hiPSC-based disease models. PMID:24315443

  8. Human iPSC-based Modeling of Late-Onset Disease via Progerin-induced Aging

    PubMed Central

    Miller, Justine D.; Ganat, Yosif M.; Kishinevsky, Sarah; Bowman, Robert L.; Liu, Becky; Tu, Edmund Y.; Mandal, Pankaj; Vera, Elsa; Shim, Jae-won; Kriks, Sonja; Taldone, Tony; Fusaki, Noemi; Tomishima, Mark J.; Krainc, Dimitri; Milner, Teresa A.; Rossi, Derrick J.; Studer, Lorenz

    2014-01-01

    Summary Reprogramming somatic cells to induced pluripotent stem cells (iPSCs), resets their identity back to an embryonic age, and thus presents a significant hurdle for modeling late-onset disorders. In this study, we describe a strategy for inducing aging-related features in human iPSC-derived lineages and apply it to the modeling of Parkinson’s disease (PD). Our approach involves expression of progerin, a truncated form of lamin A associated with premature aging. We found that expression of progerin in iPSC-derived fibroblasts and neurons induces multiple aging-related markers and characteristics, including dopamine-specific phenotypes such as neuromelanin accumulation. Induced aging in PD-iPSC-derived dopamine neurons revealed disease phenotypes that require both aging and genetic susceptibility, such as pronounced dendrite degeneration, progressive loss of tyrosine-hydroxylase (TH) expression and enlarged mitochondria or Lewy body-precursor inclusions. Thus, our study suggests that progerin-induced aging can be used to reveal late-onset age-related disease features in hiPSC-based disease models. PMID:24315443

  9. Modelling Anopheles gambiae s.s. Population Dynamics with Temperature- and Age-Dependent Survival.

    PubMed

    Christiansen-Jucht, Céline; Erguler, Kamil; Shek, Chee Yan; Basáñez, María-Gloria; Parham, Paul E

    2015-06-01

    Climate change and global warming are emerging as important threats to human health, particularly through the potential increase in vector- and water-borne diseases. Environmental variables are known to affect substantially the population dynamics and abundance of the poikilothermic vectors of disease, but the exact extent of this sensitivity is not well established. Focusing on malaria and its main vector in Africa, Anopheles gambiae sensu stricto, we present a set of novel mathematical models of climate-driven mosquito population dynamics motivated by experimental data suggesting that in An. gambiae, mortality is temperature and age dependent. We compared the performance of these models to that of a "standard" model ignoring age dependence. We used a longitudinal dataset of vector abundance over 36 months in sub-Saharan Africa for comparison between models that incorporate age dependence and one that does not, and observe that age-dependent models consistently fitted the data better than the reference model. This highlights that including age dependence in the vector component of mosquito-borne disease models may be important to predict more reliably disease transmission dynamics. Further data and studies are needed to enable improved fitting, leading to more accurate and informative model predictions for the An. gambiae malaria vector as well as for other disease vectors. PMID:26030468

  10. Modelling Anopheles gambiae s.s. Population Dynamics with Temperature- and Age-Dependent Survival

    PubMed Central

    Christiansen-Jucht, Céline; Erguler, Kamil; Shek, Chee Yan; Basáñez, María-Gloria; Parham, Paul E.

    2015-01-01

    Climate change and global warming are emerging as important threats to human health, particularly through the potential increase in vector- and water-borne diseases. Environmental variables are known to affect substantially the population dynamics and abundance of the poikilothermic vectors of disease, but the exact extent of this sensitivity is not well established. Focusing on malaria and its main vector in Africa, Anopheles gambiae sensu stricto, we present a set of novel mathematical models of climate-driven mosquito population dynamics motivated by experimental data suggesting that in An. gambiae, mortality is temperature and age dependent. We compared the performance of these models to that of a “standard” model ignoring age dependence. We used a longitudinal dataset of vector abundance over 36 months in sub-Saharan Africa for comparison between models that incorporate age dependence and one that does not, and observe that age-dependent models consistently fitted the data better than the reference model. This highlights that including age dependence in the vector component of mosquito-borne disease models may be important to predict more reliably disease transmission dynamics. Further data and studies are needed to enable improved fitting, leading to more accurate and informative model predictions for the An. gambiae malaria vector as well as for other disease vectors. PMID:26030468

  11. Atomistic Model of Physical Ageing in Se-rich As-Se Glasses

    SciTech Connect

    Golovchak,R.; Shpotyuk, O.; Kozdras, A.; Bureau, B.; Vlcek, M.; Ganjoo, A.; Jain, H.

    2007-01-01

    Thermal, optical, X-ray excited and magnetic methods were used to develop a microstructural model of physical ageing in Se-rich glasses. The glass composition As10Se90, possessing a typical cross-linked chain structure, was chosen as a model object for the investigations. The effect of physical ageing in this glass was revealed by differential scanning calorimetry, whereas the corresponding changes in its atomic arrangement were studied by extended X-ray absorption fine structure, Raman and solid-state 77Se nuclear magnetic resonance spectroscopy. Straightening-shrinkage processes are shown to be responsible for the physical ageing in this Se-rich As-Se glass.

  12. A Dimensional Liability Model of Age Differences in Mental Disorder Prevalence: Evidence from a National Sample

    PubMed Central

    Hoertel, Nicolas; McMahon, Kibby; Olfson, Mark; Wall, Melanie M.; Rodríguez-Fernández, Jorge Mario; Lemogne, Cédric; Limosin, Frédéric; Blanco, Carlos

    2015-01-01

    Recent theories have proposed a metastructure that organizes related mental disorders into broad dimensions of psychopathology (i.e., internalizing and externalizing dimensions). Prevalence rates of most mental disorders, when examined independently, are substantially lower in older than in younger adults, which may affect this metastructure. Within a nationally representative sample, the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; N = 43,093), we developed a dimensional liability model of common psychiatric disorders to clarify whether aging affects specific disorders or general dimensions of psychopathology. Significant age differences existed across age groups (18-24, 25-34, 35-44, 45-54, 55-64, 65-75 and 75+), such that older adults showed lower prevalence rates of most disorders compared to younger adults. We next investigated patterns of disorder comorbidity for past-year psychiatric disorders and found that a distress-fear-externalizing liability model fit the data well. This model was age-group invariant and indicated that that the observed lower prevalence of mental disorders with advancing age originates from lower average means on externalizing and internalizing liability dimensions. This unifying dimensional liability model of age and mental disorder comorbidity can help inform the role of aging on mental disorder prevalence for research and intervention efforts, and service planning for the impending crisis in geriatric mental health. PMID:25858414

  13. A dimensional liability model of age differences in mental disorder prevalence: evidence from a national sample.

    PubMed

    Hoertel, Nicolas; McMahon, Kibby; Olfson, Mark; Wall, Melanie M; Rodríguez-Fernández, Jorge Mario; Lemogne, Cédric; Limosin, Frédéric; Blanco, Carlos

    2015-05-01

    Recent theories have proposed a metastructure that organizes related mental disorders into broad dimensions of psychopathology (i.e., internalizing and externalizing dimensions). Prevalence rates of most mental disorders, when examined independently, are substantially lower in older than in younger adults, which may affect this metastructure. Within a nationally representative sample, the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; N = 43,093), we developed a dimensional liability model of common psychiatric disorders to clarify whether aging affects specific disorders or general dimensions of psychopathology. Significant age differences existed across age groups (18-24, 25-34, 35-44, 45-54, 55-64, 65-75 and 75+), such that older adults showed lower prevalence rates of most disorders compared to younger adults. We next investigated patterns of disorder comorbidity for past-year psychiatric disorders and found that a distress-fear-externalizing liability model fit the data well. This model was age-group invariant and indicated that the observed lower prevalence of mental disorders with advancing age originates from lower average means on externalizing and internalizing liability dimensions. This unifying dimensional liability model of age and mental disorder comorbidity can help inform the role of aging on mental disorder prevalence for research and intervention efforts, and service planning for the impending crisis in geriatric mental health. PMID:25858414

  14. A Drosophila model for age-associated changes in sleep:wake cycles.

    PubMed

    Koh, Kyunghee; Evans, Joshua M; Hendricks, Joan C; Sehgal, Amita

    2006-09-12

    One of the most consistent behavioral changes that occurs with age in humans is the loss of sleep consolidation. This can be quite disruptive and yet little is known about its underlying basis. To better understand the effects of aging on sleep:wake cycles, we sought to study this problem in Drosophila melanogaster, a powerful system for research on aging and behavior. By assaying flies of different ages as well as monitoring individual flies constantly over the course of their lifetime, we found that the strength of sleep:wake cycles decreased and that sleep became more fragmented with age in Drosophila. These changes in sleep:wake cycles became faster or slower with manipulations of ambient temperature that decreased or increased lifespan, respectively, demonstrating that they are a function of physiological rather than chronological age. The effect of temperature on lifespan was not mediated by changes in overall activity level or sleep amount. Flies treated with the oxidative stress-producing reagent paraquat showed a breakdown of sleep:wake cycles similar to that seen with aging, leading us to propose that the accumulation of oxidative damage with age contributes to the changes in rhythm and sleep. Together, these findings establish Drosophila as a valuable model for studying age-associated sleep fragmentation and breakdown of rhythm strength, and indicate that these changes in sleep:wake cycles are an integral part of the physiological aging process. PMID:16938867

  15. Compensatory renal hypertrophy and the handling of an acute nephrotoxicant in a model of aging.

    PubMed

    Oliveira, Cláudia S; Joshee, Lucy; Zalups, Rudolfs K; Bridges, Christy C

    2016-03-01

    Aging often results in progressive losses of functioning nephrons, which can lead to a significant reduction in overall renal function. Because of age-related pathological changes, the remaining functional nephrons within aged kidneys may be unable to fully counteract physiological and/or toxicological challenges. We hypothesized that when the total functional renal mass of aged rats is reduced by 50%, the nephrons within the remnant kidney do not fully undergo the functional and physiological changes that are necessary to maintain normal fluid and solute homeostasis. We also tested the hypothesis that the disposition and handling of a nephrotoxicant are altered significantly in aged kidneys following an acute, 50% reduction in functional renal mass. To test these hypotheses, we examined molecular indices of renal cellular hypertrophy and the disposition of inorganic mercury (Hg(2+)), a model nephrotoxicant, in young control, young uninephrectomized (NPX), aged control and aged NPX Wistar rats. We found that the process of aging reduces the ability of the remnant kidney to undergo compensatory renal growth. In addition, we found that an additional reduction in renal mass in aged animals alters the disposition of Hg(2+) and potentially alters the risk of renal intoxication by this nephrotoxicant. To our knowledge, this study represents the first report of the handling of a nephrotoxicant in an aged animal following a 50% reduction in functional renal mass. PMID:26768998

  16. Age equity in different models of primary care practice in Ontario

    PubMed Central

    Dahrouge, Simone; Hogg, William; Tuna, Meltem; Russell, Grant; Devlin, Rose Ann; Tugwell, Peter; Kristjansson, Elizabeth

    2011-01-01

    Abstract Objective To assess whether the model of service delivery affects the equity of the care provided across age groups. Design Cross-sectional study. Setting Ontario. Participants One hundred thirty-seven practices, including traditional fee-for-service practices, salaried community health centres (CHCs), and capitation-based family health networks and health service organizations. Main outcome measures To compare the quality of care across age groups using multilevel linear or logistic regressions. Health service delivery measures and health promotion were assessed through patient surveys (N = 5111), which were based on the Primary Care Assessment Tool, and prevention and chronic disease management were assessed, based on Canadian recommendations for care, through chart abstraction (N = 4 108). Results Older individuals reported better health service delivery in all models. This age effect ranged from 1.9% to 5.7%, and was larger in the 2 capitation-based models. Individuals aged younger than 30 years attending CHCs had more features of disadvantage (ie, living below the poverty line and without high school education) and were more likely than older individuals to report discussing at least 1 health promotion subject at the index visit. These differences were deemed an appropriate response to greater needs in these younger individuals. The prevention score showed an age-sex interaction in all models, with adherence to recommended care dropping with age for women. These results are largely attributable to the fact that maneuvers recommended for younger women are considerably more likely to be performed than other maneuvers. Chronic disease management scores showed an inverted U relationship with age in fee-for-service practices, family health networks, and health service organizations but not in CHCs. Conclusion The salaried model might have an organizational structure that is more conducive to providing appropriate care across age groups. The thrust toward

  17. Verification of relationship model between Korean new elderly class’s recovery resilience and productive aging

    PubMed Central

    Cho, Gun-Sang; Kim, Dae-Sung; Yi, Eun-Surk

    2015-01-01

    The purpose of this study is to verification of relationship model between Korean new elderly class’s recovery resilience and productive aging. As of 2013, this study sampled preliminary elderly people in Gyeonggi-do and other provinces nationwide. Data from a total of effective 484 subjects was analyzed. The collected data was processed using the IBM SPSS 20.0 and AMOS 20.0, and underwent descriptive statistical analysis, confirmatory factor analysis, and structure model verification. The path coefficient associated with model fitness was examined. The standardization path coefficient between recovery resilience and productive aging is β=0.975 (t=14.790), revealing a statistically significant positive effect. Thus, it was found that the proposed basic model on the direct path of recovery resilience and productive aging was fit for the model. PMID:26730383

  18. Specific age-related molecular alterations in the cerebellum of Down syndrome mouse models.

    PubMed

    Créau, Nicole; Cabet, Eva; Daubigney, Fabrice; Souchet, Benoit; Bennaï, Soumia; Delabar, Jean

    2016-09-01

    Down syndrome, or trisomy 21, has been modeled with various trisomic and transgenic mice to help understand the consequences of an altered gene dosage in brain development and function. Though Down syndrome has been associated with premature aging, little is known about the molecular and cellular alterations that target brain function. To help identify alterations at specific ages, we analyzed the cerebellum of Ts1Cje mice, trisomic for 77 HSA21 orthologs, at three ages-young (4 months), middle-age (12 months), and old (17 months)-compared to age-matched controls. Quantification of neuronal and glial markers (n=11) revealed increases in GFAP, with an age effect, and S100B, with age and genotype effects. The genotype effect on S100B with age was unexpected as Ts1Cje has only two copies of the S100b gene. Interestingly, the different increase in GFAP observed between Ts1Cje (trisomic segment includes Pcp4 gene) and controls was magnified in TgPCP4 mice (1 extra copy of the human PCP4 gene) at the same age. S100B increase was not found in the TgPCP4 confirming a difference of regulation with aging for GFAP and S100B and excluding the calcium signaling regulator, Pcp4, as a potential candidate for increase of S100B in the Ts1Cje. To understand these differences, comparison of GFAP and S100B immunostainings at young and middle-age were performed. Immunohistochemical detection of differences in GFAP and S100B localization with aging implicate S100B+ oligodendrocytes as a new phenotypic target in this specific aging process. PMID:27297494

  19. Chronic and progressive Parkinson's disease MPTP model in adult and aged mice.

    PubMed

    Muñoz-Manchado, Ana B; Villadiego, Javier; Romo-Madero, Sonia; Suárez-Luna, Nela; Bermejo-Navas, Alfonso; Rodríguez-Gómez, José A; Garrido-Gil, Pablo; Labandeira-García, José L; Echevarría, Miriam; López-Barneo, José; Toledo-Aral, Juan J

    2016-01-01

    Despite the different animal models of Parkinson's disease developed during the last years, they still present limitations modelling the slow and progressive process of neurodegeneration. Here, we undertook a histological, neurochemical and behavioural analysis of a new chronic parkinsonian mouse model generated by the subcutaneous administration of low doses of MPTP (20 mg/kg, 3 times per week) for 3 months, using both young adult and aged mice. The MPTP-induced nigrostriatal neurodegeneration was progressive and was accompanied by a decrease in striatal dopamine levels and motor impairment. We also demonstrated the characteristic neuroinflammatory changes (microglial activation and astrogliosis) associated with the neurodegenerative process. Aged animals showed both a faster time course of neurodegeneration and an altered neuroinflammatory response. The long-term systemic application of low MPTP doses did not induce any increase in mortality in either young adult or aged mice and better resembles the slow evolution of the neurodegenerative process. This treatment could be useful to model different stages of Parkinson's disease, providing a better understanding of the pathophysiology of the disease and facilitating the testing of both protective and restorative treatments. Here, we show a new chronic and progressive parkinsonian mouse model, in young and aged mice. This model produces a stable degeneration of the dopaminergic nigrostriatal pathway, continuous neuroinflammatory reaction and motor deficits. Aged animals showed a faster neurodegeneration and an altered neuroinflammatory response. This treatment could be useful to model different stages of PD and to test both protective and restorative therapeutic approaches. PMID:26500044

  20. Markov Chain-Like Quantum Biological Modeling of Mutations, Aging, and Evolution

    PubMed Central

    Djordjevic, Ivan B.

    2015-01-01

    Recent evidence suggests that quantum mechanics is relevant in photosynthesis, magnetoreception, enzymatic catalytic reactions, olfactory reception, photoreception, genetics, electron-transfer in proteins, and evolution; to mention few. In our recent paper published in Life, we have derived the operator-sum representation of a biological channel based on codon basekets, and determined the quantum channel model suitable for study of the quantum biological channel capacity. However, this model is essentially memoryless and it is not able to properly model the propagation of mutation errors in time, the process of aging, and evolution of genetic information through generations. To solve for these problems, we propose novel quantum mechanical models to accurately describe the process of creation spontaneous, induced, and adaptive mutations and their propagation in time. Different biological channel models with memory, proposed in this paper, include: (i) Markovian classical model, (ii) Markovian-like quantum model, and (iii) hybrid quantum-classical model. We then apply these models in a study of aging and evolution of quantum biological channel capacity through generations. We also discuss key differences of these models with respect to a multilevel symmetric channel-based Markovian model and a Kimura model-based Markovian process. These models are quite general and applicable to many open problems in biology, not only biological channel capacity, which is the main focus of the paper. We will show that the famous quantum Master equation approach, commonly used to describe different biological processes, is just the first-order approximation of the proposed quantum Markov chain-like model, when the observation interval tends to zero. One of the important implications of this model is that the aging phenotype becomes determined by different underlying transition probabilities in both programmed and random (damage) Markov chain-like models of aging, which are mutually

  1. Down syndrome as a model of DNA polymerase beta haploinsufficiency and accelerated aging.

    PubMed

    Patterson, David; Cabelof, Diane C

    2012-04-01

    Down syndrome is a condition of intellectual disability characterized by accelerated aging. As with other aging syndromes, evidence accumulated over the past several decades points to a DNA repair defect inherent in Down syndrome. This evidence has led us to suggest that Down syndrome results in reduced DNA base excision repair (BER) capacity, and that this contributes to the genomic instability and the aging phenotype of Down syndrome. We propose important roles for microRNA and/or folate metabolism and oxidative stress in the dysregulation of BER in Down syndrome. Further, we suggest these pathways are involved in the leukemogenesis of Down syndrome. We have reviewed the role of BER in the processing of oxidative stress, and the impact of folate depletion on BER capacity. Further, we have reviewed the role that loss of BER, specifically DNA polymerase beta, plays in accelerating the rate of aging. Like that seen in the DNA polymerase beta heterozygous mouse, the aging phenotype of Down syndrome is subtle, unlike the aging phenotypes seen in the classical progeroid syndromes and mouse models of aging. As such, Down syndrome may provide a model for elucidating some of the basic mechanisms of aging. PMID:22019846

  2. Hutchinson-Gilford progeria syndrome as a model for vascular aging.

    PubMed

    Brassard, Jonathan A; Fekete, Natalie; Garnier, Alain; Hoesli, Corinne A

    2016-02-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder caused by a de novo genetic mutation that leads to the accumulation of a splicing isoform of lamin A termed progerin. Progerin expression alters the organization of the nuclear lamina and chromatin. The life expectancy of HGPS patients is severely reduced due to critical cardiovascular defects. Progerin also accumulates in an age-dependent manner in the vascular cells of adults that do not carry genetic mutations associated with HGPS. The molecular mechanisms that lead to vascular dysfunction in HGPS may therefore also play a role in vascular aging. The vascular phenotypic and molecular changes observed in HGPS are strikingly similar to those seen with age, including increased senescence, altered mechanotransduction and stem cell exhaustion. This article discusses the similarities and differences between age-dependent and HGPS-related vascular aging to highlight the relevance of HGPS as a model for vascular aging. Induced pluripotent stem cells derived from HGPS patients are suggested as an attractive model to study vascular aging in order to develop novel approaches to treat cardiovascular disease. PMID:26330290

  3. Using remotely-sensed multispectral imagery to build age models for alluvial fan surfaces

    NASA Astrophysics Data System (ADS)

    D'Arcy, Mitch; Mason, Philippa J.; Roda Boluda, Duna C.; Whittaker, Alexander C.; Lewis, James

    2016-04-01

    Accurate exposure age models are essential for much geomorphological field research, and generally depend on laboratory analyses such as radiocarbon, cosmogenic nuclide, or luminescence techniques. These approaches continue to revolutionise geomorphology, however they cannot be deployed remotely or in situ in the field. Therefore other methods are still needed for producing preliminary age models, performing relative dating of surfaces, or selecting sampling sites for the laboratory analyses above. With the widespread availability of detailed multispectral imagery, a promising approach is to use remotely-sensed data to discriminate surfaces with different ages. Here, we use new Landsat 8 Operational Land Imager (OLI) multispectral imagery to characterise the reflectance of 35 alluvial fan surfaces in the semi-arid Owens Valley, California. Alluvial fans are useful landforms to date, as they are widely used to study the effects of tectonics, climate and sediment transport processes on source-to-sink sedimentation. Our target fan surfaces have all been mapped in detail in the field, and have well-constrained exposure ages ranging from modern to ~ 125 ka measured using a high density of 10Be cosmogenic nuclide samples. Despite all having similar granitic compositions, the spectral properties of these surfaces vary systematically with their exposure ages. Older surfaces demonstrate a predictable shift in reflectance across the visible and short-wave infrared spectrum. Simple calculations, such as the brightness ratios of different wavelengths, generate sensitive power law relationships with exposure age that depend on post-depositional alteration processes affecting these surfaces. We investigate what these processes might be in this dryland location, and evaluate the potential for using remotely-sensed multispectral imagery for developing surface age models. The ability to remotely sense relative exposure ages has useful implications for preliminary mapping, selecting

  4. Depot-Specific Changes in Fat Metabolism with Aging in a Type 2 Diabetic Animal Model

    PubMed Central

    Park, Se Eun; Choi, Jung Mook; Chang, Eugene; Rhee, Eun-Jung; Lee, Won-Young; Oh, Ki Won; Park, Sung Woo; Kang, Eun Seok; Lee, Hyun Chul

    2016-01-01

    Visceral fat accretion is a hallmark of aging and is associated with aging-induced metabolic dysfunction. PPARγ agonist was reported to improve insulin sensitivity by redistributing fat from visceral fat to subcutaneous fat. The purpose of this study was to investigate the underlying mechanisms by which aging affects adipose tissue remodeling in a type 2 diabetic animal model and through which PPARγ activation modulates aging-related fat tissue distribution. At the ages of 21, 31 and 43 weeks, OLETF rats as an animal model of type 2 diabetes were evaluated for aging-related effects on adipose tissue metabolism in subcutaneous and visceral fat depots. During aging, the ratio of visceral fat weight to subcutaneous fat weight (V/S ratio) increased. Aging significantly increased the mRNA expression of genes involved in lipogenesis such as lipoprotein lipase, fatty acid binding protein aP2, lipin 1, and diacylglycerol acyltransferase 1, which were more prominent in visceral fat than subcutaneous fat. The mRNA expression of adipose triglyceride lipase, which is involved in basal lipolysis and fatty acid recycling, was also increased, more in visceral fat compared to subcutaneous fat during aging. The mRNA levels of the genes associated with lipid oxidation were increased, whereas the mRNA levels of genes associated with energy expenditure showed no significant change during aging. PPARγ agonist treatment in OLETF rats resulted in fat redistribution with a decreasing V/S ratio and improved glucose intolerance. The genes involved in lipogenesis decreased in visceral fat of the PPARγ agonist-treated rats. During aging, fat distribution was changed by stimulating lipid uptake and esterification in visceral fat rather than subcutaneous fat, and by altering the lipid oxidation. PMID:26894429

  5. Depot-Specific Changes in Fat Metabolism with Aging in a Type 2 Diabetic Animal Model.

    PubMed

    Park, Se Eun; Park, Cheol-Young; Choi, Jung Mook; Chang, Eugene; Rhee, Eun-Jung; Lee, Won-Young; Oh, Ki Won; Park, Sung Woo; Kang, Eun Seok; Lee, Hyun Chul; Cha, Bong Soo

    2016-01-01

    Visceral fat accretion is a hallmark of aging and is associated with aging-induced metabolic dysfunction. PPARγ agonist was reported to improve insulin sensitivity by redistributing fat from visceral fat to subcutaneous fat. The purpose of this study was to investigate the underlying mechanisms by which aging affects adipose tissue remodeling in a type 2 diabetic animal model and through which PPARγ activation modulates aging-related fat tissue distribution. At the ages of 21, 31 and 43 weeks, OLETF rats as an animal model of type 2 diabetes were evaluated for aging-related effects on adipose tissue metabolism in subcutaneous and visceral fat depots. During aging, the ratio of visceral fat weight to subcutaneous fat weight (V/S ratio) increased. Aging significantly increased the mRNA expression of genes involved in lipogenesis such as lipoprotein lipase, fatty acid binding protein aP2, lipin 1, and diacylglycerol acyltransferase 1, which were more prominent in visceral fat than subcutaneous fat. The mRNA expression of adipose triglyceride lipase, which is involved in basal lipolysis and fatty acid recycling, was also increased, more in visceral fat compared to subcutaneous fat during aging. The mRNA levels of the genes associated with lipid oxidation were increased, whereas the mRNA levels of genes associated with energy expenditure showed no significant change during aging. PPARγ agonist treatment in OLETF rats resulted in fat redistribution with a decreasing V/S ratio and improved glucose intolerance. The genes involved in lipogenesis decreased in visceral fat of the PPARγ agonist-treated rats. During aging, fat distribution was changed by stimulating lipid uptake and esterification in visceral fat rather than subcutaneous fat, and by altering the lipid oxidation. PMID:26894429

  6. Modeling age-specific cancer incidences using logistic growth equations: implications for data collection.

    PubMed

    Shen, Xing-Rong; Feng, Rui; Chai, Jing; Cheng, Jing; Wang, De-Bin

    2014-01-01

    Large scale secular registry or surveillance systems have been accumulating vast data that allow mathematical modeling of cancer incidence and mortality rates. Most contemporary models in this regard use time series and APC (age-period-cohort) methods and focus primarily on predicting or analyzing cancer epidemiology with little attention being paid to implications for designing cancer registry, surveillance or evaluation initiatives. This research models age-specific cancer incidence rates using logistic growth equations and explores their performance under different scenarios of data completeness in the hope of deriving clues for reshaping relevant data collection. The study used China Cancer Registry Report 2012 as the data source. It employed 3-parameter logistic growth equations and modeled the age-specific incidence rates of all and the top 10 cancers presented in the registry report. The study performed 3 types of modeling, namely full age-span by fitting, multiple 5-year- segment fitting and single-segment fitting. Measurement of model performance adopted adjusted goodness of fit that combines sum of squred residuals and relative errors. Both model simulation and performance evalation utilized self-developed algorithms programed using C# languade and MS Visual Studio 2008. For models built upon full age-span data, predicted age-specific cancer incidence rates fitted very well with observed values for most (except cervical and breast) cancers with estimated goodness of fit (Rs) being over 0.96. When a given cancer is concerned, the R valuae of the logistic growth model derived using observed data from urban residents was greater than or at least equal to that of the same model built on data from rural people. For models based on multiple-5-year-segment data, the Rs remained fairly high (over 0.89) until 3-fourths of the data segments were excluded. For models using a fixed length single-segment of observed data, the older the age covered by the corresponding

  7. Antioxidant effect of garlic and aged black garlic in animal model of type 2 diabetes mellitus

    PubMed Central

    Lee, Young-Min; Gweon, Oh-Cheon; Seo, Yeong-Ju; Im, Jieun; Kang, Min-Jung; Kim, Myo-Jeong

    2009-01-01

    Hyperglycemia in the diabetic state increases oxidative stress and antioxidant therapy can be strongly correlated with decreased risks for diabetic complications. The purpose of this study is to determine antioxidant effect of garlic and aged black garlic in animal model of type 2 diabetes. The antioxidant activity of garlic and aged black garlic was measured as the activity in scavenging free radicals by the trolox equivalent antioxidant capacity (TEAC) assay. Three week-old db/db mice were fed AIN-93G diet or diet containing 5% freeze-dried garlic or aged black garlic for 7 weeks after 1 week of adaptation. Hepatic levels of lipid peroxides and activities of antioxidant enzymes were measured. TEAC values of garlic and aged black garlic were 13.3 ± 0.5 and 59.2 ± 0.8 µmol/g wet weight, respectively. Consumption of aged black garlic significantly decreased hepatic thiobarbituric acid reactive substances (TBARS) level compared with the garlic group which showed lower TBARS level than control group (p<0.05). Activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of garlic and aged black garlic group were significantly elevated compared to the control group. Catalase (CAT) activity of aged black garlic group was increased compared with the control group. These results show that aged black garlic exerts stronger antioxidant activity than garlic in vitro and in vivo, suggesting garlic and aged black garlic, to a greater extent, could be useful in preventing diabetic complications. PMID:20016716

  8. Increasing pulse wave velocity in a realistic cardiovascular model does not increase pulse pressure with age

    PubMed Central

    Mohiuddin, Mohammad W.; Rihani, Ryan J.; Laine, Glen A.

    2012-01-01

    The mechanism of the well-documented increase in aortic pulse pressure (PP) with age is disputed. Investigators assuming a classical windkessel model believe that increases in PP arise from decreases in total arterial compliance (Ctot) and increases in total peripheral resistance (Rtot) with age. Investigators assuming a more sophisticated pulse transmission model believe PP rises because increases in pulse wave velocity (cph) make the reflected pressure wave arrive earlier, augmenting systolic pressure. It has recently been shown, however, that increases in cph do not have a commensurate effect on the timing of the reflected wave. We therefore used a validated, large-scale, human arterial system model that includes realistic pulse wave transmission to determine whether increases in cph cause increased PP with age. First, we made the realistic arterial system model age dependent by altering cardiac output (CO), Rtot, Ctot, and cph to mimic the reported changes in these parameters from age 30 to 70. Then, cph was theoretically maintained constant, while Ctot, Rtot, and CO were altered. The predicted increase in PP with age was similar to the observed increase in PP. In a complementary approach, Ctot, Rtot, and CO were theoretically maintained constant, and cph was increased. The predicted increase in PP was negligible. We found that increases in cph have a limited effect on the timing of the reflected wave but cause the system to degenerate into a windkessel. Changes in PP can therefore be attributed to a decrease in Ctot. PMID:22561301

  9. Realistic modeling of environmental tracer migration and composite age distributions in a pine beetle impacted watershed

    NASA Astrophysics Data System (ADS)

    Engdahl, N. B.; Maxwell, R. M.

    2013-12-01

    Descriptions of age in hydrologic systems are often limited to the residence time in the surface water system or the subsurface with little consideration of the interaction between the two, or the different ways geochemical tracers are altered in each domain. Understanding the way tracer concentrations change in each domain is essential to accurate estimation of age, but few models have explicitly modeled the fully coupled system or considered distributions of age. This work presents a numerical laboratory that is specifically designed to investigate composite age distributions (CADs) and their connections to tracer concentrations. The CAD is defined here as the combination of the residence time distributions for surface flows, vadose zone, and groundwater systems, providing an accounting for the total time a discrete fluid parcel has spent within the integrated hydrologic system. CADs are generated by particle tracking through a fully integrated flow model and it is straight forward to realistically simulate the transport of environmental tracers such as 85-Krypton and 39-Argon that can be used for estimating water ages. This framework allows explicit modeling of the different processes in each domain that affect tracer concentrations including the mixing of different source waters, partial equilibrium with the atmosphere through the vadose zone, evaporative enrichment in surface flows, and diffusive fractionation in the subsurface. Transient forcings, such as seasonal or daily variations in precipitation, can also be simulated and the effects of this transience on concentrations and age distributions can easily be investigated. The model domain used to demonstrate these tools is based on a well-defined watershed within Rocky Mountain National Park. The mountain pine beetle has devastated the park's forests and the massive tree-kill has begun to affect the quality and distribution of the water resources. Accurate modeling of the CADs in the park is a crucial step

  10. A Third Note on Ageing in a Library Circulation Model: Applications to Future Use and Relegation.

    ERIC Educational Resources Information Center

    Burrell, Quentin L.

    1987-01-01

    Describes a circulation model for academic research libraries which uses the mixed Poisson model, incorporating ageing of library materials, to predict future use of monographs and to suggest weeding procedures based on frequency of circulation. Longitudinal studies are examined and statistical details are appended. (Author/LRW)