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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. 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

  16. 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

  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. 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

  20. 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

  1. 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

  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. 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

  8. 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)

  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. 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

  5. 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

  6. 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

  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

    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.

  3. 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

  4. 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.

  5. 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.

  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. 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.

  3. 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

  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. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  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. 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

  12. 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

  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. 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

  15. 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.

  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. 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.

  3. 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.

  4. 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.

  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. 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.

  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

    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

  17. 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

  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. 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

  3. 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.

  4. 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…

  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. 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)

  19. 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…

  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. 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

  7. 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.

  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. 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.

  2. 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.

  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. 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…

  6. 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…

  7. 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.…

  8. 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…

  9. 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…

  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. 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

  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. 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

  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. 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.

  18. 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

  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. 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.

  2. 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

  3. 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

  4. 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

  5. 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

  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. 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

  2. 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

  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. METHODS FOR MODELING PARTICLE DEPOSITION AS A FUNCTION OF AGE. (R827352C004)

    EPA Science Inventory

    The purpose of this paper is to review the application of mathematical models of inhaled particle deposition to people of various ages. The basic considerations of aerosol physics, biological characteristics and model structure are presented along with limitations inherent in ...

  11. Multilevel Risk Models for Retrospective Age-of-Onset Data: School Children's First Cigarette.

    ERIC Educational Resources Information Center

    Pickles, Andrew; Pickering, Kevin; Taylor, Colin; Sutton, Stephen; Yang, Shuying

    2001-01-01

    Describes a random effects discrete time survival model that addresses problems of measurement error and sample design complexities. Demonstrates the effectiveness of the model in an analysis of retrospective report data on the age of onset of smoking from two cross-sectional school-based studies. (JPB)

  12. 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)

  13. The Cache la Poudre river basin snow water equivalent modeling with NewAge-JGrass

    NASA Astrophysics Data System (ADS)

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

    2013-08-01

    The paper presents a snow water equivalent model as part of the hydrological modeling system NewAge-JGrass. The model take in account of the main physical processes influencing the snow melting (precipitation form separation, melting and freezing modeling) coupled with the snowpack mass conservation equation. The snow melting depends not only on the air temperature but also on the radiation received by the pixel. The model is perfectly integrated in the NewAge-JGrass modeling system and uses many of its components such as shortwave radiation balance, krigings and automatic calibration algorithms. As all the NewAge-JGrass components, the presented model can be executed both in raster and in vector mode and the simulation time step can be daily, hourly or sub-hourly as the user needs. The model is applied on the Cache la Poudre river basin (CO, USA). Three are the applications presented in the paper. Firstly, the simulation of snow water equivalent in three different measurement stations is performed. Model parameters are calibrated and model performances are quantitatively computed by comparing simulated and measured snow water equivalent time series. Indices of goodness of fit such as Kling-Gupta Efficiency, Index of Agreement and Percentage Bias are computed. Secondly, the representativeness of the model parameters in different locations is discussed. Finally a raster mode application is performed: snow water equilvalent maps on the whole Cache la Poudre river are computed. In all the applications the model performance are satisfactory in term of goodness of fitting measured snow water equivalent time series. The integration of the model in the NewAge-JGrass system allows the used to o enjoy all the component of the system: input data computation, output maps visualizetion in the GIS JGrass, model parameters automatic calibration.

  14. Estimating Black Carbon Aging Time-Scales with a Particle-Resolved Aerosol Model

    SciTech Connect

    Riemer, Nicole; West, Matt; Zaveri, Rahul A.; Easter, Richard C.

    2010-01-13

    Understanding the aging process of aerosol particles is important for assessing their chemical reactivity, cloud condensation nuclei activity, radiative properties and health impacts. In this study we investigate the aging of black carbon containing particles in an idealized urban plume using a new approach, the particleresolved aerosol model PartMC-MOSAIC. We present a method to estimate aging time-scales using an aging criterion based on cloud condensation nuclei activation. The results show a separation into a daytime regime where condensation dominates and a nighttime regime where coagulation dominates. For the chosen urban plume scenario, depending on the supersaturation threshold, the values for the aging timescales vary between 0.06 hours and 10 hours during the day, and between 6 hours and 20 hours during the night.

  15. Behavior problems at ages 6 and 11 and high school academic achievement: longitudinal latent variable modeling.

    PubMed

    Breslau, Naomi; Breslau, Joshua; Miller, Elizabeth; Raykov, Tenko

    2011-02-28

    Previous studies documented long-run effects of behavior problems at the start of school on academic achievement. However, these studies did not examine whether the observed effects of early behavior problems are explained by more proximate behavior problems, given the tendency of children's behavior problems to persist. Latent variable modeling was applied to estimate the effects of behavior problems at ages 6 and 11 on academic achievement at age 17, using data from a longitudinal study (n=823). Behavior problems at ages 6 and 11, each stage independently of the other, predicted lower math and reading test scores at age 17, controlling for intelligence quotient (IQ), birth weight, maternal characteristics, family and community environment, and taking into account behavior problems at age 17. Behavior problems at the start of school, independent of later behavior problems, exert lingering effects on achievement by impeding the acquisition of cognitive skills that are the foundation for later academic progress. PMID:20719395

  16. Lens opacity based modelling of the age-related straylight increase.

    PubMed

    Rozema, Jos J; Sanchez, Victoria; Artal, Natalia; Gramajo, Ana L; Torres, Eduardo; Luna, Jose D; Iribarren, Rafael; Tassignon, Marie-José; Juarez, Claudio P

    2015-12-01

    This work studies ethnic and geographical differences in the age-related straylight increase by means of a stochastic model and unpublished lens opacity data of 559 residents of Villa Maria (Argentina), as well as data of 912 Indonesian subjects published previously by Husain et al. For both cohorts the prevalence of each type and grade of lens opacity was determined as a function of age, from which a stochastic model was derived capable of simulating the lens opacity prevalence for both populations. These simulated lens opacity data were then converted to estimated straylight by means of an equation derived from previously recorded data of 107 eyes with varying degrees of cataract. Based on these opacity templates 2500 random sets of subject age and lens opacity data were generated by the stochastic model for each dataset, from which estimated straylight could be calculated. For the Argentinian data the estimated straylight was found to closely resemble the published models for age-related straylight increase. For younger eyes the straylight variation of the model was the same as what was previously published (in both cases ±0.200logunits), which doubled in size for older eyes. For the Indonesian data, however, this age-related straylight increase was found to be fundamentally different from the published age model. This suggests that current normative curves for age-related straylight increase may not always be appropriate for non-European populations, and that the inter-individual straylight variations in young, healthy eyes may possibly be due to variations in lens opacities. PMID:26459146

  17. Lithium-ion Open Circuit Voltage (OCV) curve modelling and its ageing adjustment

    NASA Astrophysics Data System (ADS)

    Lavigne, L.; Sabatier, J.; Francisco, J. Mbala; Guillemard, F.; Noury, A.

    2016-08-01

    This paper is a contribution to lithium-ion batteries modelling taking into account aging effects. It first analyses the impact of aging on electrode stoichiometry and then on lithium-ion cell Open Circuit Voltage (OCV) curve. Through some hypotheses and an appropriate definition of the cell state of charge, it shows that each electrode equilibrium potential, but also the whole cell equilibrium potential can be modelled by a polynomial that requires only one adjustment parameter during aging. An adjustment algorithm, based on the idea that for two fixed OCVs, the state of charge between these two equilibrium states is unique for a given aging level, is then proposed. Its efficiency is evaluated on a battery pack constituted of four cells.

  18. The effects of aging on the BTBR mouse model of autism spectrum disorder

    PubMed Central

    Jasien, Joan M.; Daimon, Caitlin M.; Wang, Rui; Shapiro, Bruce K.; Martin, Bronwen; Maudsley, Stuart

    2014-01-01

    Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder characterized by alterations in social functioning, communicative abilities, and engagement in repetitive or restrictive behaviors. The process of aging in individuals with autism and related neurodevelopmental disorders is not well understood, despite the fact that the number of individuals with ASD aged 65 and older is projected to increase by over half a million individuals in the next 20 years. To elucidate the effects of aging in the context of a modified central nervous system, we investigated the effects of age on the BTBR T + tf/j mouse, a well characterized and widely used mouse model that displays an ASD-like phenotype. We found that a reduction in social behavior persists into old age in male BTBR T + tf/j mice. We employed quantitative proteomics to discover potential alterations in signaling systems that could regulate aging in the BTBR mice. Unbiased proteomic analysis of hippocampal and cortical tissue of BTBR mice compared to age-matched wild-type controls revealed a significant decrease in brain derived neurotrophic factor and significant increases in multiple synaptic markers (spinophilin, Synapsin I, PSD 95, NeuN), as well as distinct changes in functional pathways related to these proteins, including “Neural synaptic plasticity regulation” and “Neurotransmitter secretion regulation.” Taken together, these results contribute to our understanding of the effects of aging on an ASD-like mouse model in regards to both behavior and protein alterations, though additional studies are needed to fully understand the complex interplay underlying aging in mouse models displaying an ASD-like phenotype. PMID:25225482

  19. The Quadratic Hazard Model for Analyzing Longitudinal Data on Aging, Health, and the Life Span

    PubMed Central

    Yashin, A.I.; Arbeev, K.G.; Akushevich, I.; Kulminski, A.; Ukraintseva, S.V.; Stallard, E.; Land, K.C.

    2012-01-01

    A better understanding of processes and mechanisms linking human aging with changes in health status and survival requires methods capable of analyzing new data that take into account knowledge about these processes accumulated in the field. In this paper, we describe an approach to analyses of longitudinal data based on the use of stochastic process models of human aging, health, and longevity which allows for incorporating state of the art advances in aging research into the model structure. In particular, the model incorporates the notions of resistance to stresses, adaptive capacity, and “optimal” (normal) physiological states. To capture the effects of exposure to persistent external disturbances, the notions of allostatic adaptation and allostatic load are introduced. These notions facilitate the description and explanation of deviations of individuals’ physiological indices from their normal states, which increase the chances of disease development and death. The model provides a convenient conceptual framework for comprehensive systemic analyses of aging-related changes in humans using longitudinal data and linking these changes with genotyping profiles, morbidity, and mortality risks. The model is used for developing new statistical methods for analyzing longitudinal data on aging, health, and longevity. PMID:22633776

  20. Predictors of age-associated decline in maximal aerobic capacity: a comparison of four statistical models.

    PubMed

    Rosen, M J; Sorkin, J D; Goldberg, A P; Hagberg, J M; Katzel, L I

    1998-06-01

    Studies assessing changes in maximal aerobic capacity (VO2 max) associated with aging have traditionally employed the ratio of VO2 max to body weight. Log-linear, ordinary least-squares, and weighted least-squares models may avoid some of the inherent weaknesses associated with the use of ratios. In this study we used four different methods to examine the age-associated decline in VO2 max in a cross-sectional sample of 276 healthy men, aged 45-80 yr. Sixty-one of the men were aerobically trained athletes, and the remainder were sedentary. The model that accounted for the largest proportion of variance was a weighted least-squares model that included age, fat-free mass, and an indicator variable denoting exercise training status. The model accounted for 66% of the variance in VO2 max and satisfied all the important general linear model assumptions. The other approaches failed to satisfy one or more of these assumptions. The results indicated that VO2 max declines at the same rate in athletic and sedentary men (0.24 l/min or 9%/decade) and that 35% of this decline (0.08 l . min-1 . decade-1) is due to the age-associated loss of fat-free mass. PMID:9609813

  1. Government, industry, and university partnerships: A model for the knowledge age

    NASA Astrophysics Data System (ADS)

    Varner, Michael O.

    1996-03-01

    New technologies are transforming the industrial economy into a marketplace driven by information and knowledge. The depth, breadth, and rate of technology development, however, overwhelms our ability to absorb, process, and recall new information. Moreover, the bright future enabled by the knowledge age cannot be realized without the development of new organizational models and philosophies. This paper discusses the necessity for business, government, and universities to create inter-institutional partnerships in order to accommodate change and flourish in the knowledge age.

  2. Age-Dependent Metastatic Spread and Survival: Cancer of Unknown Primary as a Model

    PubMed Central

    Hemminki, Kari; Pavlidis, Nicholas; Tsilidis, Konstantinos K.; Sundquist, Kristina; Ji, Jianguang

    2016-01-01

    In order to describe a novel approach for the clinical study of metastases, we provide here age-specific incidence and survival data for cancer of unknown primary (CUP). Metastases in various organs are found at CUP diagnosis, which have implications for prognosis, and we hypothesize similar prognostic implications for metastases found at diagnosis of primary cancers. We identified 33,224 CUP patients from the Swedish Cancer Registry and calculated incidence rates (IRs) for CUP development. Cox proportional hazards regression models were performed to estimate hazard ratios (HRs) for relative survival in CUP patients compared to the general population. In age-group specific analyses, a maximal IR was reached at age 85–89 years, followed by a marked decline to age 90+ (7-fold in men and 3-fold in women). The overall HR for relative survival declined systematically by age. CUP may be applied as an epidemiological age-incidence model for cancer metastases providing evidence in line with autopsy data that the metastatic potential, as shown by the incidence of CUP, appears to weaken markedly at age 85 years, depending on metastatic locations. The relative death rates were highest among young patients, which was probably entirely due to the low death rates in young background population. PMID:27009354

  3. Simulations of a mortality plateau in the sexual Penna model for biological aging

    NASA Astrophysics Data System (ADS)

    Schwämmle, V.; de Oliveira, S. Moss

    2005-09-01

    The Penna model is a strategy to simulate the genetic dynamics of age-structured populations, in which the individual genomes are represented by bit strings. It provides a simple metaphor for the evolutionary process in terms of the mutation accumulation theory. In its original version, an individual dies due to inherited diseases when its current number of accumulated mutations, n , reaches a threshold value T . Since the mean number of diseases increases with age, the probability to die is zero for very young ages (nage, we test several other functions that may or may not slightly increase the death probability at young ages (nages. By imposing certain conditions, it has been possible to obtain a clear plateau using the Penna model. However, a more realistic one appears when a modified version, that keeps the population size fixed without fluctuations, is used. We also find a relation between the birth rate, the age structure of the population, and the death probability.

  4. Understanding the physiology of the ageing individual: computational modelling of changes in metabolism and endurance.

    PubMed

    van Beek, Johannes H G M; Kirkwood, Thomas B L; Bassingthwaighte, James B

    2016-04-01

    Ageing and lifespan are strongly affected by metabolism. The maximal possible uptake of oxygen is not only a good predictor of performance in endurance sports, but also of life expectancy. Figuratively speaking, healthy ageing is a competitive sport. Although the root cause of ageing is damage to macromolecules, it is the balance with repair processes that is decisive. Reduced or intermittent nutrition, hormones and intracellular signalling pathways that regulate metabolism have strong effects on ageing. Homeostatic regulatory processes tend to keep the environment of the cells within relatively narrow bounds. On the other hand, the body is constantly adapting to physical activity and food consumption. Spontaneous fluctuations in heart rate and other processes indicate youth and health. A (homeo)dynamic aspect of homeostasis deteriorates with age. We are now in a position to develop computational models of human metabolism and the dynamics of heart rhythm and oxygen transport that will advance our understanding of ageing. Computational modelling of the connections between dietary restriction, metabolism and protein turnover may increase insight into homeostasis of the proteins in our body. In this way, the computational reconstruction of human physiological processes, the Physiome, can help prevent frailty and age-related disease. PMID:27051508

  5. Voluntary Medical Male Circumcision for HIV Prevention in Swaziland: Modeling the Impact of Age Targeting

    PubMed Central

    Kripke, Katharine; Okello, Velephi; Maziya, Vusi; Benzerga, Wendy; Mirira, Munamato; Gold, Elizabeth; Schnure, Melissa; Sgaier, Sema; Castor, Delivette; Reed, Jason

    2016-01-01

    Background Voluntary medical male circumcision (VMMC) for HIV prevention has been a priority for Swaziland since 2009. Initially focusing on men ages 15–49, the Ministry of Health reduced the minimum age for VMMC from 15 to 10 years in 2012, given the existing demand among 10- to 15-year-olds. To understand the implications of focusing VMMC service delivery on specific age groups, the MOH undertook a modeling exercise to inform policy and implementation in 2013–2014. Methods and Findings The impact and cost of circumcising specific age groups were assessed using the Decision Makers’ Program Planning Tool, Version 2.0 (DMPPT 2.0), a simple compartmental model. We used age-specific HIV incidence from the Swaziland HIV Incidence Measurement Survey (SHIMS). Population, mortality, births, and HIV prevalence were imported from a national Spectrum/Goals model recently updated in consultation with country stakeholders. Baseline male circumcision prevalence was derived from the most recent Swaziland Demographic and Health Survey. The lowest numbers of VMMCs per HIV infection averted are achieved when males ages 15–19, 20–24, 25–29, and 30–34 are circumcised, although the uncertainty bounds for the estimates overlap. Circumcising males ages 25–29 and 20–24 provides the most immediate reduction in HIV incidence. Circumcising males ages 15–19, 20–24, and 25–29 provides the greatest magnitude incidence reduction within 15 years. The lowest cost per HIV infection averted is achieved by circumcising males ages 15–34: $870 U.S. dollars (USD). Conclusions The potential impact, cost, and cost-effectiveness of VMMC scale-up in Swaziland are not uniform. They vary by the age group of males circumcised. Based on the results of this modeling exercise, the Ministry of Health’s Swaziland Male Circumcision Strategic and Operational Plan 2014–2018 adopted an implementation strategy that calls for circumcision to be scaled up to 50% coverage for neonates, 80

  6. Trajectories of Sleep Complaints From Early Midlife to Old Age: Longitudinal Modeling Study

    PubMed Central

    Salo, Paula; Vahtera, Jussi; Ferrie, Jane E.; Akbaraly, Tasnime; Goldberg, Marcel; Zins, Marie; Pentti, Jaana; Virtanen, Marianna; Shipley, Martin J.; Singh-Manoux, Archana; Dauvilliers, Yves; Kivimaki, Mika

    2012-01-01

    Study Objectives: To estimate trajectories of sleep lost over worry as a function of age, using longitudinal modeling, and compare these trajectories with those for insomnia symptoms. Design and Setting: Data from two prospective, occupational cohorts (the Whitehall II and Finnish Public Sector studies) comprising 84,384 observations from four to eight repeat measurements in 1985-2010. Participants: There were 16,408 men and women age 34-79 yr. Measurements and Results: Age-related trajectories of sleep lost over worry and insomnia symptoms (sleep initiation or maintenance problems, nonrefreshing sleep) were estimated using repeated-measures log-binomial regression analysis and generalized estimating equations. These analyses were adjusted for year of birth and time of measurement to minimize confounding by cohort or period effects. The prevalence ratio for insomnia symptoms was higher in older age groups compared with participants age 34-45 yr. In contrast, the age-related trajectory of sleep lost over worry included two phases: a period of high prevalence of sleep complaints at age 34-60 yr followed by a declining trajectory at older ages. Compared with participants age 34-45 yr, prevalence ratios for sleep lost over worry were 0.63 (0.49-0.80) and 0.59 (0.41-0.84) in the Whitehall II study participants ages 61-65 and 71-79 years. Corresponding figures were 0.62 (0.52-0.75) and 0.46 (0.32-0.66) in the Finnish Public Sector study. Conclusion: This study shows a general age-related decrease in sleep lost over worry between late midlife and old age, a pattern strikingly different from the age-related increase in insomnia symptoms. Citation: Salo P; Vahtera J; Ferrie JE; Akbaraly T; Goldberg M; Zins M; Pentti J; Virtanen M; Shipley MJ; Singh-Manoux A; Dauvilliers Y; Kivimaki M. Trajectories of sleep complaints from early midlife to old age: longitudinal modeling study. SLEEP 2012;35(11):1559-1568. PMID:23115405

  7. Evaluation of Aged Garlic Extract Neuroprotective Effect in a Focal Model of Cerebral Ischemia

    NASA Astrophysics Data System (ADS)

    Aguilera, Penélope; Maldonado, Perla D.; Ortiz-Plata, Alma; Barrera, Diana; Chánez-Cárdenas, María Elena

    2008-02-01

    The oxidant species generated in cerebral ischemia have been implicated as important mediators of neuronal injury through damage to lipids, DNA, and proteins. Since ischemia as well as reperfusion insults generate oxidative stress, the administration of antioxidants may limit oxidative damage and ameliorate disease progression. The present work shows the transitory neuroprotective effect of the aged garlic extract (AGE) administration (a proposed antioxidant compound) in a middle cerebral artery occlusion (MCAO) model in rats and established its therapeutic window. To determine the optimal time of administration, animal received AGE (1.2 mL/kg) intraperitoneally 30 min before onset of reperfusion (-0.5 R), at the beginning of reperfusion (0R), or 1 h after onset of reperfusion (1R). Additional doses were administrated after 1, 2, or 3 h after onset of reperfusion. To establish the therapeutic window of AGE, the infarct area was determined for each treatment after different times of reperfusion. Results show that the administration of AGE at the onset of reperfusion reduced the infarct area by 70% (evaluated after 2 h reperfusion). The therapeutic window of AGE was determined. Repeated doses did not extend the temporal window of protection. A significant reduction in the nitrotyrosine level was observed in the brain tissue subjected to MCAO after AGE treatment at the onset of reperfusion. Data in the present work show that AGE exerts a transitory neuroprotective effect in response to ischemia/reperfusion-induced neuronal injury.

  8. The African Turquoise Killifish: A Model for Exploring Vertebrate Aging and Diseases in the Fast Lane.

    PubMed

    Harel, Itamar; Brunet, Anne

    2015-01-01

    Why and how organisms age remains a mystery, and it defines one of the biggest challenges in biology. Aging is also the primary risk factor for many human pathologies, such as cancer, diabetes, cardiovascular diseases, and neurodegenerative diseases. Thus, manipulating the aging rate and potentially postponing the onset of these devastating diseases could have a tremendous impact on human health. Recent studies, relying primarily on nonvertebrate short-lived model systems, have shown the importance of both genetic and environmental factors in modulating the aging rate. However, relatively little is known about aging in vertebrates or what processes may be unique and specific to these complex organisms. Here we discuss how advances in genomics and genome editing have significantly expanded our ability to probe the aging process in a vertebrate system. We highlight recent findings from a naturally short-lived vertebrate, the African turquoise killifish, which provides an attractive platform for exploring mechanisms underlying vertebrate aging and age-related diseases. PMID:26642856

  9. Accounting for Age Uncertainty in Growth Modeling, the Case Study of Yellowfin Tuna (Thunnus albacares) of the Indian Ocean

    PubMed Central

    Dortel, Emmanuelle; Massiot-Granier, Félix; Rivot, Etienne; Million, Julien; Hallier, Jean-Pierre; Morize, Eric; Munaron, Jean-Marie; Bousquet, Nicolas; Chassot, Emmanuel

    2013-01-01

    Age estimates, typically determined by counting periodic growth increments in calcified structures of vertebrates, are the basis of population dynamics models used for managing exploited or threatened species. In fisheries research, the use of otolith growth rings as an indicator of fish age has increased considerably in recent decades. However, otolith readings include various sources of uncertainty. Current ageing methods, which converts an average count of rings into age, only provide periodic age estimates in which the range of uncertainty is fully ignored. In this study, we describe a hierarchical model for estimating individual ages from repeated otolith readings. The model was developed within a Bayesian framework to explicitly represent the sources of uncertainty associated with age estimation, to allow for individual variations and to include knowledge on parameters from expertise. The performance of the proposed model was examined through simulations, and then it was coupled to a two-stanza somatic growth model to evaluate the impact of the age estimation method on the age composition of commercial fisheries catches. We illustrate our approach using the saggital otoliths of yellowfin tuna of the Indian Ocean collected through large-scale mark-recapture experiments. The simulation performance suggested that the ageing error model was able to estimate the ageing biases and provide accurate age estimates, regardless of the age of the fish. Coupled with the growth model, this approach appeared suitable for modeling the growth of Indian Ocean yellowfin and is consistent with findings of previous studies. The simulations showed that the choice of the ageing method can strongly affect growth estimates with subsequent implications for age-structured data used as inputs for population models. Finally, our modeling approach revealed particularly useful to reflect uncertainty around age estimates into the process of growth estimation and it can be applied to any

  10. Accounting for age uncertainty in growth modeling, the case study of yellowfin tuna (Thunnus albacares) of the Indian Ocean.

    PubMed

    Dortel, Emmanuelle; Massiot-Granier, Félix; Rivot, Etienne; Million, Julien; Hallier, Jean-Pierre; Morize, Eric; Munaron, Jean-Marie; Bousquet, Nicolas; Chassot, Emmanuel

    2013-01-01

    Age estimates, typically determined by counting periodic growth increments in calcified structures of vertebrates, are the basis of population dynamics models used for managing exploited or threatened species. In fisheries research, the use of otolith growth rings as an indicator of fish age has increased considerably in recent decades. However, otolith readings include various sources of uncertainty. Current ageing methods, which converts an average count of rings into age, only provide periodic age estimates in which the range of uncertainty is fully ignored. In this study, we describe a hierarchical model for estimating individual ages from repeated otolith readings. The model was developed within a Bayesian framework to explicitly represent the sources of uncertainty associated with age estimation, to allow for individual variations and to include knowledge on parameters from expertise. The performance of the proposed model was examined through simulations, and then it was coupled to a two-stanza somatic growth model to evaluate the impact of the age estimation method on the age composition of commercial fisheries catches. We illustrate our approach using the sagittal otoliths of yellowfin tuna of the Indian Ocean collected through large-scale mark-recapture experiments. The simulation performance suggested that the ageing error model was able to estimate the ageing biases and provide accurate age estimates, regardless of the age of the fish. Coupled with the growth model, this approach appeared suitable for modeling the growth of Indian Ocean yellowfin and is consistent with findings of previous studies. The simulations showed that the choice of the ageing method can strongly affect growth estimates with subsequent implications for age-structured data used as inputs for population models. Finally, our modeling approach revealed particularly useful to reflect uncertainty around age estimates into the process of growth estimation and it can be applied to any

  11. Modeling transient groundwater age in the Middle Wairarapa Valley, New Zealand

    NASA Astrophysics Data System (ADS)

    Evison, R.; Daughney, C.; Jackson, B. M.; Toews, M. W.; Cornaton, F. J.; Gyopari, M.; McAllister, D.

    2013-12-01

    Age information provides insights into groundwater flow and transport processes and thus enables better groundwater management. It is accepted that groundwater is composed of a mixture of water with different ages. For example, a groundwater sample with an old mean age may still contain a fraction of young water; recent contamination is therefore a potential risk that may not be conveyed by consideration of the mean age alone. This project focuses on catchment-scale evaluation of the full distribution of groundwater age as a function of space and time in the 270 km2 Middle Wairarapa Valley, New Zealand. The Wairarapa Valley exhibits complex interactions between its rivers and shallow aquifers. Agriculture is an integral part of the region with widespread irrigation and nutrient application. This requires effective regional management due to the risk of contamination and depletion of groundwater reservoirs. The starting point was a transient finite-element groundwater flow model originally developed by Greater Wellington Regional Council (GWRC). The GWRC flow model was converted to simulate transport of the age tracer tritium using Ground Water (GW) software. There are several techniques to calibrate groundwater models and assess appropriate parameter values, all of which have the problem of non-uniqueness. In this study the Gauss-Marquardt-Levenberg method was utilized to calibrate the model (through PEST), but in order to increase robustness, a classic Monte Carlo method with uniform random sampling was also used to sample the domain's global range of flow and transport parameters. This provided an increased measure of confidence in model output, as the global range of parameter values could be explored, which is not achieved via the localized Gauss-Marquardt-Levenberg parameter estimation scheme. The calibration objective with both methods used least squares minimization between the simulated and observed hydraulic head levels and tritium concentrations. GW

  12. Dynamic analysis of a hepatitis B model with three-age-classes

    NASA Astrophysics Data System (ADS)

    Zhang, Suxia; Zhou, Yicang

    2014-07-01

    Based on the fact that the likelihood of becoming chronically infected is dependent on age at primary infection Kane (1995) [2], Edmunds et al. (1993) [3], Medley et al. (2001) [4], and Ganem and Prince (2004) [6], we formulate a hepatitis B transmission model with three age classes. The reproduction number, R0 is defined and the dynamical behavior of the model is analyzed. It is proved that the disease-free equilibrium is globally stable if R0<1, and there exists at least one endemic equilibrium and that the disease is uniformly persistent if R0>1. The unique endemic equilibrium and its global stability is obtained in a special case. Simulations are also conducted to compare the dynamical behavior of the model with and without age classes.

  13. The use of mature zebrafish (Danio rerio) as a model for human aging and disease.

    PubMed

    Keller, Evan T; Murtha, Jill M

    2004-07-01

    Zebrafish (Danio rerio) have been extensively utilized for understanding mechanisms of development. These studies have led to a wealth of resources including genetic tools, informational databases, and husbandry methods. In spite of all these resources, zebrafish have been underutilized for exploring pathophysiology of disease and the aging process. Zebrafish offer several advantages over mammalian models for these studies, including the ability to perform saturation mutagenesis and the capability to contain thousands of animals in a small space. In this review, we will discuss the use of mature zebrafish as an animal model and provide specific examples to support this novel use of zebrafish. Examples include demonstrating that clinical pathology can be performed in mature zebrafish and that age-associated changes in heat shock response can be observed in zebrafish. These highlights demonstrate the utility of zebrafish as a model for disease and aging. PMID:15533791

  14. A validated age-related normative model for male total testosterone shows increasing variance but no decline after age 40 years.

    PubMed

    Kelsey, Thomas W; Li, Lucy Q; Mitchell, Rod T; Whelan, Ashley; Anderson, Richard A; Wallace, W Hamish B

    2014-01-01

    The diagnosis of hypogonadism in human males includes identification of low serum testosterone levels, and hence there is an underlying assumption that normal ranges of testosterone for the healthy population are known for all ages. However, to our knowledge, no such reference model exists in the literature, and hence the availability of an applicable biochemical reference range would be helpful for the clinical assessment of hypogonadal men. In this study, using model selection and validation analysis of data identified and extracted from thirteen studies, we derive and validate a normative model of total testosterone across the lifespan in healthy men. We show that total testosterone peaks [mean (2.5-97.5 percentile)] at 15.4 (7.2-31.1) nmol/L at an average age of 19 years, and falls in the average case [mean (2.5-97.5 percentile)] to 13.0 (6.6-25.3) nmol/L by age 40 years, but we find no evidence for a further fall in mean total testosterone with increasing age through to old age. However we do show that there is an increased variation in total testosterone levels with advancing age after age 40 years. This model provides the age related reference ranges needed to support research and clinical decision making in males who have symptoms that may be due to hypogonadism. PMID:25295520

  15. Modeling computer interest in older adults: the role of age, education, computer knowledge, and computer anxiety.

    PubMed

    Ellis, D; Allaire, J C

    1999-09-01

    We proposed a mediation model to examine the effects of age, education, computer knowledge, and computer anxiety on computer interest in older adults. We hypothesized that computer knowledge and computer anxiety would fully mediate the effects of age and education on computer interest. A sample of 330 older adults from local senior-citizen apartment buildings completed a survey that included an assessment of the constructs included in the model. Using structural equation modeling, we found that the results supported the hypothesized mediation model. In particular, the effect of computer knowledge operated on computer interest through computer anxiety. The effect of age was not fully mitigated by the other model variables, indicating the need for future research that identifies and models other correlates of age and computer interest. The most immediate application of this research is the finding that a simple 3-item instrument can be used to assess computer interest in older populations. This will help professionals plan and implement computer services in public-access settings for older adults. An additional application of this research is the information it provides for training program designers. PMID:10665203

  16. A New, Discontinuous 2 Phases of Aging Model: Lessons from Drosophila melanogaster

    PubMed Central

    Tricoire, Hervé; Rera, Michael

    2015-01-01

    Aging is commonly described as being a continuous process affecting progressively organisms as time passes. This process results in a progressive decrease in individuals fitness through a wide range of both organismal–decreased motor activity, fertility, resistance to stress–and molecular phenotypes–decreased protein and energy homeostasis, impairment of insulin signaling. In the past 20 years, numerous genes have been identified as playing a major role in the aging process, yet little is known about the events leading to that loss of fitness. We recently described an event characterized by a dramatic increase of intestinal permeability to a blue food dye in aging flies committed to die within a few days. Importantly, flies showing this so called ‘Smurf’ phenotype are the only ones, among a population, to show various age-related changes and exhibit a high-risk of impending death whatever their chronological age. Thus, these observations suggest that instead of being one continuous phenomenon, aging may be a discontinuous process well described by at least two distinguishable phases. In this paper we addressed this hypothesis by implementing a new 2 Phases of Aging mathematiCal model (2PAC model) to simulate longevity curves based on the simple hypothesis of two consecutive phases of lifetime presenting different properties. We first present a unique equation for each phase and discuss the biological significance of the 3 associated parameters. Then we evaluate the influence of each parameter on the shape of survival curves. Overall, this new mathematical model, based on simple biological observations, is able to reproduce many experimental longevity curves, supporting the existence of 2 phases of aging exhibiting specific properties and separated by a dramatic transition that remains to be characterized. Moreover, it indicates that Smurf survival can be approximated by one single constant parameter for a broad range of genotypes that we have tested under

  17. Quantification the Effect of Ageing on Characteristics of the Photoplethysmogram Using an Optimized Windkessel Model

    PubMed Central

    Doostdar, H; Khalilzadeh, MA

    2014-01-01

    Background: With increasing age, some changes appeared in specifications of vessels which including dimensions and elasticity in theirs. The changes in parameters such as resistance, inertance and compliance vessels appear and eventually changes in the environmental pulse releases are in circulation. These changes clearly appear in specification of photoplethysmogram particularly in the size and position signals second peak is observed. Aim and scope: The aim of study was to Circulatory system modeling using windkessel electrical model  for evalution blood flow  and Its matching with the photoplethysmogram’s signal for investigate the reasons for changes of Characteristics of the Photoplethysmogram. The first purpose of this paper is to examine the age-related parameters in the Photoplethysmogram’s signal and finally the diagnosis of cardiovascular disease using the model and photoplethysmogram’s signal. Methods: In this study we followed some of these effects to the circulatory system by using the windkessel electrical model. The algorithm in this project appeared by optimization with the matrix coefficients of state space windkessel electrical model. Optimize of the coefficients matching with the output of the model and the photoplethysmogram’s signal. Photoplethysmogram’s signals from 50 healthy subjects with the age range of 20 to 50 years, shows that outputs the model and photoplethysmogram’s signal in terms of error rate and cross-correlation algorithm in a fully automate, was consistent. Wavelength of the Photoplethysmogram’s signals were 950 nm and The sampling rate was set at 50 Hz. Results: Simulation results show that aging reduces the signal amplitude and delay of the second peak occurs. These changes were seen as reduce the rate of compliance and increase the rate of resistance and inertance windkessel electrical model of circulation. Conclusion: The high accuracy of the results led to being able to identify the age range and some

  18. Modeling the formation and aging of secondary organic aerosols during CalNex 2010

    NASA Astrophysics Data System (ADS)

    Hayes, P. L.; Ortega, A. M.; Ahmadov, R.; McKeen, S. A.; Washenfelder, R. A.; Alvarez, S.; Rappenglueck, B.; Holloway, J. S.; Gilman, J. B.; Kuster, W. C.; De Gouw, J. A.; Zotter, P.; Prevot, A. S.; Kleindienst, T. E.; Offenberg, J. H.; Jimenez, J. L.

    2012-12-01

    Several traditional and recently proposed models are applied to predict the concentrations and properties of secondary organic aerosols (SOA) and organic gases at the Pasadena ground site during the CalNex campaign. The models are constrained with and compared against results from available observations. The CalNex campaign and specifically the Pasadena ground site featured a large and sophisticated suite of aerosol and gas phase instrumentation, and thus, it provides a unique opportunity to test SOA models under conditions of strong urban emissions at a range of low photochemical ages. The oxidation of volatile organic compounds (VOCs) using an updated traditional model cannot explain the observed ambient SOA, and under-predicts the measurements by a factor of ~40. Similarly, after accounting for the multi-generation oxidation of VOCs using a volatility basis set (VBS) approach as described by Tsimpidi et al. (2010), SOA is still under-predicted by a factor of ~8. For SOA formed from VOCs (V-SOA) the dominant precursors are aromatics (xylenes, toluene, and trimethylbenzenes). The model SOA formed from the oxidation of primary semivolatile and intermediate volatility organic compounds (P-S/IVOCs, producing SI-SOA) is also predicted using the parameterizations of Robinson et al. (2007) and Grieshop et al. (2009), and the properties of V-SOA + SI-SOA are compared against the measured O:C and volatility. We also compare the results of the different models against fossil/non-fossil carbon measurements as well as tracers of different SOA precursors. Potential Aerosol Mass (PAM) measurements of the SOA forming potential of the Pasadena air masses are also compared against that predicted by the models. The PAM analysis allows for model/measurement comparisons of SOA properties over a range of photochemical ages spanning almost two weeks. Using the V-SOA model, at low photochemical ages (< 1 day) the modeled PAM V-SOA is less than the measured PAM SOA, similar to the

  19. A model for antagonistic pleiotropic gene action for mortality and advanced age.

    PubMed

    Toupance, B; Godelle, B; Gouyon, P H; Schächter, F

    1998-06-01

    Association or linkage studies involving control and long-lived populations provide information on genes that influence longevity. However, the relationship between allele-specific differences in survival and the genetic structure of aging cohorts remains unclear. We model a heterogeneous cohort comprising several genotypes differing in age-specific mortality. In its most general form, without any specific assumption regarding the shape of mortality curves, the model permits derivation of a fundamental property underlying abrupt age-related changes in the composition of a cohort. The model is applied to sex-specific survival curves taken from period life tables, and Gompertz-Makeham mortality coefficients are calculated for the French population. Then, adjustments are performed under Gompertz-Makeham mortality functions for three genotypes composing a heterogeneous cohort, under the constraint of fitting the resultant mortality to the real French population mortality obtained from life tables. Multimodal curves and divergence after the 8th decade appear as recurrent features of the frequency trajectories. Finally, a fit to data previously obtained at the angiotensin-converting-enzyme locus is realized, explaining what had seemed to be paradoxical results-namely, that the frequency of a genotype known as a cardiovascular risk factor was increased in centenarians. Our results help explain the well-documented departure from Gompertz-Makeham mortality kinetics at older ages. The implications of our model are discussed in the context of known genetic effects on human longevity and age-related pathologies. Since antagonistic pleiotropy between early and late survival emerges as a general rule, extrapolating the effects measured for a gene in a particular age class to other ages could be misleading. PMID:9585593

  20. Aging and serum MCP-1 are associated with gut microbiome composition in a murine model

    PubMed Central

    Conley, Melissa N.; Wong, Carmen P.; Duyck, Kyle M.; Hord, Norman; Ho, Emily

    2016-01-01

    Introduction. Age is the primary risk factor for major human chronic diseases, including cardiovascular disorders, cancer, type 2 diabetes, and neurodegenerative diseases. Chronic, low-grade, systemic inflammation is associated with aging and the progression of immunosenescence. Immunosenescence may play an important role in the development of age-related chronic disease and the widely observed phenomenon of increased production of inflammatory mediators that accompany this process, referred to as “inflammaging.” While it has been demonstrated that the gut microbiome and immune system interact, the relationship between the gut microbiome and age remains to be clearly defined, particularly in the context of inflammation. The aim of our study was to clarify the associations between age, the gut microbiome, and pro-inflammatory marker serum MCP-1 in a C57BL/6 murine model. Results. We used 16S rRNA gene sequencing to profile the composition of fecal microbiota associated with young and aged mice. Our analysis identified an association between microbiome structure and mouse age and revealed specific groups of taxa whose abundances stratify young and aged mice. This includes the Ruminococcaceae, Clostridiaceae, and Enterobacteriaceae. We also profiled pro-inflammatory serum MCP-1 levels of each mouse and found that aged mice exhibited elevated serum MCP-1, a phenotype consistent with inflammaging. Robust correlation tests identified several taxa whose abundance in the microbiome associates with serum MCP-1 status, indicating that they may interact with the mouse immune system. We find that taxonomically similar organisms can exhibit differing, even opposite, patterns of association with the host immune system. We also find that many of the OTUs that associate with serum MCP-1 stratify individuals by age. Discussion. Our results demonstrate that gut microbiome composition is associated with age and the pro-inflammatory marker, serum MCP-1. The correlation between age

  1. Aging and serum MCP-1 are associated with gut microbiome composition in a murine model.

    PubMed

    Conley, Melissa N; Wong, Carmen P; Duyck, Kyle M; Hord, Norman; Ho, Emily; Sharpton, Thomas J

    2016-01-01

    Introduction. Age is the primary risk factor for major human chronic diseases, including cardiovascular disorders, cancer, type 2 diabetes, and neurodegenerative diseases. Chronic, low-grade, systemic inflammation is associated with aging and the progression of immunosenescence. Immunosenescence may play an important role in the development of age-related chronic disease and the widely observed phenomenon of increased production of inflammatory mediators that accompany this process, referred to as "inflammaging." While it has been demonstrated that the gut microbiome and immune system interact, the relationship between the gut microbiome and age remains to be clearly defined, particularly in the context of inflammation. The aim of our study was to clarify the associations between age, the gut microbiome, and pro-inflammatory marker serum MCP-1 in a C57BL/6 murine model. Results. We used 16S rRNA gene sequencing to profile the composition of fecal microbiota associated with young and aged mice. Our analysis identified an association between microbiome structure and mouse age and revealed specific groups of taxa whose abundances stratify young and aged mice. This includes the Ruminococcaceae, Clostridiaceae, and Enterobacteriaceae. We also profiled pro-inflammatory serum MCP-1 levels of each mouse and found that aged mice exhibited elevated serum MCP-1, a phenotype consistent with inflammaging. Robust correlation tests identified several taxa whose abundance in the microbiome associates with serum MCP-1 status, indicating that they may interact with the mouse immune system. We find that taxonomically similar organisms can exhibit differing, even opposite, patterns of association with the host immune system. We also find that many of the OTUs that associate with serum MCP-1 stratify individuals by age. Discussion. Our results demonstrate that gut microbiome composition is associated with age and the pro-inflammatory marker, serum MCP-1. The correlation between age

  2. Advanced age negatively impacts survival in an experimental brain tumor model.

    PubMed

    Ladomersky, Erik; Zhai, Lijie; Gritsina, Galina; Genet, Matthew; Lauing, Kristen L; Wu, Meijing; James, C David; Wainwright, Derek A

    2016-09-01

    Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, with an average age of 64 years at the time of diagnosis. To study GBM, a number of mouse brain tumor models have been utilized. In these animal models, subjects tend to range from 6 to 12 weeks of age, which is analogous to that of a human teenager. Here, we examined the impact of age on host immunity and the gene expression associated with immune evasion in immunocompetent mice engrafted with syngeneic intracranial GL261. The data indicate that, in mice with brain tumors, youth conveys an advantage to survival. While age did not affect the tumor-infiltrating T cell phenotype or quantity, we discovered that old mice express higher levels of the immunoevasion enzyme, IDO1, which was decreased by the presence of brain tumor. Interestingly, other genes associated with promoting immunosuppression including CTLA-4, PD-L1 and FoxP3, were unaffected by age. These data highlight the possibility that IDO1 contributes to faster GBM outgrowth with advanced age, providing rationale for future investigation into immunotherapeutic targeting in the future. PMID:27493076

  3. 230Th-234U Model-Ages of Some Uranium Standard Reference Materials

    SciTech Connect

    Williams, R W; Gaffney, A M; Kristo, M J; Hutcheon, I D

    2009-05-28

    The 'age' of a sample of uranium is an important aspect of a nuclear forensic investigation and of the attribution of the material to its source. To the extent that the sample obeys the standard rules of radiochronometry, then the production ages of even very recent material can be determined using the {sup 230}Th-{sup 234}U chronometer. These standard rules may be summarized as (a) the daughter/parent ratio at time=zero must be known, and (b) there has been no daughter/parent fractionation since production. For most samples of uranium, the 'ages' determined using this chronometer are semantically 'model-ages' because (a) some assumption of the initial {sup 230}Th content in the sample is required and (b) closed-system behavior is assumed. The uranium standard reference materials originally prepared and distributed by the former US National Bureau of Standards and now distributed by New Brunswick Laboratory as certified reference materials (NBS SRM = NBL CRM) are good candidates for samples where both rules are met. The U isotopic standards have known purification and production dates, and closed-system behavior in the solid form (U{sub 3}O{sub 8}) may be assumed with confidence. We present here {sup 230}Th-{sup 234}U model-ages for several of these standards, determined by isotope dilution mass spectrometry using a multicollector ICP-MS, and compare these ages with their known production history.

  4. Modeling early-onset post-ischemic seizures in aging mice

    PubMed Central

    Wu, Chiping; Wang, Justin; Peng, Jessie; Patel, Nisarg; Huang, Yayi; Gao, Xiaoxing; Aljarallah, Salman; Eubanks, James H; McDonald, Robert; Zhang, Liang

    2016-01-01

    Stroke is the leading cause of seizures and epilepsy in the aged population, with post-stroke seizures being a poor prognostic factor. The pathological processes underlying post-stroke seizures are not well understood and studies of these seizures in aging/aged animals remain scarce. Therefore, our primary objective was to model post-stroke seizures in aging mice (C57 black strain, 16–20 month-old), with a focus on early-onset, convulsive seizures that occur within 24-hours of brain ischemia. We utilized a middle cerebral artery occlusion model and examined seizure activity and brain injury using combined behavioral and electroencephalographic monitoring and histological assessments. Aging mice exhibited vigorous convulsive seizures within hours of the middle cerebral artery occlusion. These seizures manifested with jumping, rapid running, barrel-rolling and/or falling all in the absence of hippocampal-cortical electrographic discharges. Seizure development was closely associated with severe brain injury and acute mortality. Anticonvulsive treatments after seizure occurrence offered temporary seizure control but failed to improve animal survival. A separate cohort of adult mice (6–8 months-old) exhibited analogous early-onset convulsive seizures following the middle cerebral artery occlusion but had better survival outcomes following anticonvulsive treatment. Collectively, our data suggest that early-onset convulsive seizures are a result of severe brain ischemia in aging animals. PMID:25943585

  5. Ovarian Aging-Like Phenotype in the Hyperandrogenism-Induced Murine Model of Polycystic Ovary

    PubMed Central

    Rezvanfar, Mohammad Amin; Shojaei Saadi, Habib A.; Gooshe, Maziar; Abdolghaffari, Amir Hosein; Baeeri, Maryam; Abdollahi, Mohammad

    2014-01-01

    There are prominently similar symptoms, effectors, and commonalities in the majority of characteristics between ovarian aging and polycystic ovarian syndrome (PCOS). Despite the approved role of oxidative stress in the pathogenesis of PCOS and aging, to our knowledge, the link between the PCO(S) and aging has not been investigated yet. In this study we investigated the possible exhibition of ovarian aging phenotype in murine model of PCO induced by daily oral administration of letrozole (1 mg/kg body weight) for 21 consecutive days in the female Wistar rats. Hyperandrogenization showed irregular cycles and histopathological characteristics of PCO which was associated with a significant increase in lipid peroxidation (LPO) and reactive oxygen species (ROS) and decrease in total antioxidant capacity (TAC) in serum and ovary. Moreover, serum testosterone, insulin and tumor necrosis factor-alpha (TNF-α) levels, and ovarian matrix metalloproteinase-2 (MMP-2) were increased in PCO rats compared with healthy controls, while estradiol and progesterone diminished. Almost all of these findings are interestingly found to be common with the characteristics identified with (ovarian) aging showing that hyperandrogenism-induced PCO in rat is associated with ovarian aging-like phenotypes. To our knowledge, this is the first report that provides evidence regarding the phenomenon of aging in PCO. PMID:24693338

  6. Age-associated changes in DNA methylation across multiple tissues in an inbred mouse model

    PubMed Central

    Spiers, Helen; Hannon, Eilis; Wells, Sara; Williams, Brenda; Fernandes, Cathy; Mill, Jonathan

    2016-01-01

    Epigenetic disruption has been implicated in many diseases of aging, and age-associated DNA methylation changes at specific genomic loci in humans are strongly correlated with chronological age. The aim of this study was to explore the specificity of selected age-associated differentially methylated positions (aDMPs) identified in human epidemiological studies by quantifying DNA methylation across multiple tissues in homologous regions of the murine genome. We selected four high-confidence aDMPs (located in the vicinity of the ELOVL2, GLRA1, MYOD1 and PDE4C genes) and quantified DNA methylation across these regions in four tissues (blood, lung, cerebellum and hippocampus) from male and female C57BL/6J mice, ranging in age from fetal (embryonic day 17) to 630 days. We observed tissue-specific age-associated changes in DNA methylation that was directionally consistent with those observed in humans. These findings lend further support to the notion that changes in DNA methylation are associated with chronological age and suggest that these processes are often conserved across tissues and between mammalian species. Our data highlight the relevance of utilizing model systems, in which environmental and genetic influences can be carefully controlled, for the further study of these phenomena. PMID:26861500

  7. Ovarian aging-like phenotype in the hyperandrogenism-induced murine model of polycystic ovary.

    PubMed

    Rezvanfar, Mohammad Amin; Shojaei Saadi, Habib A; Gooshe, Maziar; Abdolghaffari, Amir Hosein; Baeeri, Maryam; Abdollahi, Mohammad

    2014-01-01

    There are prominently similar symptoms, effectors, and commonalities in the majority of characteristics between ovarian aging and polycystic ovarian syndrome (PCOS). Despite the approved role of oxidative stress in the pathogenesis of PCOS and aging, to our knowledge, the link between the PCO(S) and aging has not been investigated yet. In this study we investigated the possible exhibition of ovarian aging phenotype in murine model of PCO induced by daily oral administration of letrozole (1 mg/kg body weight) for 21 consecutive days in the female Wistar rats. Hyperandrogenization showed irregular cycles and histopathological characteristics of PCO which was associated with a significant increase in lipid peroxidation (LPO) and reactive oxygen species (ROS) and decrease in total antioxidant capacity (TAC) in serum and ovary. Moreover, serum testosterone, insulin and tumor necrosis factor-alpha (TNF-α) levels, and ovarian matrix metalloproteinase-2 (MMP-2) were increased in PCO rats compared with healthy controls, while estradiol and progesterone diminished. Almost all of these findings are interestingly found to be common with the characteristics identified with (ovarian) aging showing that hyperandrogenism-induced PCO in rat is associated with ovarian aging-like phenotypes. To our knowledge, this is the first report that provides evidence regarding the phenomenon of aging in PCO. PMID:24693338

  8. Age-associated changes in DNA methylation across multiple tissues in an inbred mouse model.

    PubMed

    Spiers, Helen; Hannon, Eilis; Wells, Sara; Williams, Brenda; Fernandes, Cathy; Mill, Jonathan

    2016-03-01

    Epigenetic disruption has been implicated in many diseases of aging, and age-associated DNA methylation changes at specific genomic loci in humans are strongly correlated with chronological age. The aim of this study was to explore the specificity of selected age-associated differentially methylated positions (aDMPs) identified in human epidemiological studies by quantifying DNA methylation across multiple tissues in homologous regions of the murine genome. We selected four high-confidence aDMPs (located in the vicinity of the ELOVL2, GLRA1, MYOD1 and PDE4C genes) and quantified DNA methylation across these regions in four tissues (blood, lung, cerebellum and hippocampus) from male and female C57BL/6J mice, ranging in age from fetal (embryonic day 17) to 630 days. We observed tissue-specific age-associated changes in DNA methylation that was directionally consistent with those observed in humans. These findings lend further support to the notion that changes in DNA methylation are associated with chronological age and suggest that these processes are often conserved across tissues and between mammalian species. Our data highlight the relevance of utilizing model systems, in which environmental and genetic influences can be carefully controlled, for the further study of these phenomena. PMID:26861500

  9. Structural modeling of age specific fertility curves in Peninsular Malaysia: An approach of Lee Carter method

    NASA Astrophysics Data System (ADS)

    Hanafiah, Hazlenah; Jemain, Abdul Aziz

    2013-11-01

    In recent years, the study of fertility has been getting a lot of attention among research abroad following fear of deterioration of fertility led by the rapid economy development. Hence, this study examines the feasibility of developing fertility forecasts based on age structure. Lee Carter model (1992) is applied in this study as it is an established and widely used model in analysing demographic aspects. A singular value decomposition approach is incorporated with an ARIMA model to estimate age specific fertility rates in Peninsular Malaysia over the period 1958-2007. Residual plots is used to measure the goodness of fit of the model. Fertility index forecast using random walk drift is then utilised to predict the future age specific fertility. Results indicate that the proposed model provides a relatively good and reasonable data fitting. In addition, there is an apparent and continuous decline in age specific fertility curves in the next 10 years, particularly among mothers' in their early 20's and 40's. The study on the fertility is vital in order to maintain a balance between the population growth and the provision of facilities related resources.

  10. A four-component model of age-related memory change.

    PubMed

    Healey, M Karl; Kahana, Michael J

    2016-01-01

    We develop a novel, computationally explicit, theory of age-related memory change within the framework of the context maintenance and retrieval (CMR2) model of memory search. We introduce a set of benchmark findings from the free recall and recognition tasks that include aspects of memory performance that show both age-related stability and decline. We test aging theories by lesioning the corresponding mechanisms in a model fit to younger adult free recall data. When effects are considered in isolation, many theories provide an adequate account, but when all effects are considered simultaneously, the existing theories fail. We develop a novel theory by fitting the full model (i.e., allowing all parameters to vary) to individual participants and comparing the distributions of parameter values for older and younger adults. This theory implicates 4 components: (a) the ability to sustain attention across an encoding episode, (b) the ability to retrieve contextual representations for use as retrieval cues, (c) the ability to monitor retrievals and reject intrusions, and (d) the level of noise in retrieval competitions. We extend CMR2 to simulate a recognition memory task using the same mechanisms the free recall model uses to reject intrusions. Without fitting any additional parameters, the 4-component theory that accounts for age differences in free recall predicts the magnitude of age differences in recognition memory accuracy. Confirming a prediction of the model, free recall intrusion rates correlate positively with recognition false alarm rates. Thus, we provide a 4-component theory of a complex pattern of age differences across 2 key laboratory tasks. PMID:26501233

  11. Constitutive Modeling and Testing of Polymer Matrix Composites Incorporating Physical Aging at Elevated Temperatures

    NASA Technical Reports Server (NTRS)

    Veazie, David R.

    1998-01-01

    Advanced polymer matrix composites (PMC's) are desirable for structural materials in diverse applications such as aircraft, civil infrastructure and biomedical implants because of their improved strength-to-weight and stiffness-to-weight ratios. For example, the next generation military and commercial aircraft requires applications for high strength, low weight structural components subjected to elevated temperatures. A possible disadvantage of polymer-based composites is that the physical and mechanical properties of the matrix often change significantly over time due to the exposure of elevated temperatures and environmental factors. For design, long term exposure (i.e. aging) of PMC's must be accounted for through constitutive models in order to accurately assess the effects of aging on performance, crack initiation and remaining life. One particular aspect of this aging process, physical aging, is considered in this research.

  12. Mechanisms of Muscle Denervation in Aging: Insights from a Mouse Model of Amyotrophic Lateral Sclerosis

    PubMed Central

    Park, Kevin H.J

    2015-01-01

    Muscle denervation at the neuromuscular junction (NMJ) is thought to be a contributing factor in age-related muscle weakness. Therefore, understanding the mechanisms that modulate NMJ innervation is a key to developing therapies to combat age-related muscle weakness affecting the elderly. Two mouse models, one lacking the Cu/Zn superoxide dismutase (SOD1) gene and another harboring the transgenic mutant human SOD1 gene, display progressive changes at the NMJ, including muscle endplate fragmentation, nerve terminal sprouting, and denervation. These changes at the NMJ share many of the common features observed in the NMJs of aged mice. In this review, research findings demonstrating the effects of PGC-1α, IGF-1, GDNF, MyoD, myogenin, and miR-206 on NMJ innervation patterns in the G93A SOD1 mice will be highlighted in the context of age-related muscle denervation. PMID:26425392

  13. Decreased plasma cholesterol levels during aging in transgenic mouse models of Alzheimer's disease.

    PubMed

    Wirths, Oliver; Thelen, Karin; Breyhan, Henning; Luzón-Toro, Berta; Hoffmann, Karl-Heinz; Falkai, Peter; Lütjohann, Dieter; Bayer, Thomas A

    2006-02-01

    A large number of studies deals with the association of cholesterol and Abeta levels, however, the results are so far controversial. Whereas some studies report on increased cholesterol levels, other authors refer to an association of decreased peripheral cholesterol and the incidence of Alzheimer's disease. It is also questionable whether plasma cholesterol levels could be used as a predictive biomarker for the incidence of Alzheimer's disease. In the present report, we studied the relationship between these two parameters during aging in different transgenic mouse models of Alzheimer's disease, expressing both mutant human amyloid precursor protein and mutant human presenilin-1. Measurements of plasma cholesterol levels revealed a significant reduction in aged APP/PS1 and APP/PS1ki mice, whereas plasma levels in young and aged control mice remained almost unchanged. Furthermore, statistical analysis revealed a significant negative correlation between plasma cholesterol and brain Abeta42 levels during aging in the mice expressing both APP and PS1. PMID:16307858

  14. Evolution of collective motion in a model glass-forming liquid during physical aging

    NASA Astrophysics Data System (ADS)

    Shavit, Amit; Douglas, Jack F.; Riggleman, Robert A.

    2013-03-01

    At temperatures moderately below their glass transition temperature, the properties of many glass-forming materials can evolve slowly with time in a process known as physical aging whereby the thermodynamic, mechanical, and dynamic properties all drift towards their equilibrium values. In this work, we study the evolution of the thermodynamic and dynamic properties during physical aging for a model polymer glass. Specifically, we test the relationship between an estimate of the size of the cooperative rearrangements taking the form of strings and the effective structural relaxation time predicted by the Adam-Gibbs relationship for both an equilibrium supercooled liquid and the same fluid undergoing physical aging towards equilibrium after a series of temperature jumps. We find that there is apparently a close correlation between a structural feature of the fluid, the size of the string-like rearrangements, and the structural relaxation time, although the relationship for the aging fluid appears to be distinct from that of the fluid at equilibrium.

  15. Age-Dependent Changes in FasL (CD95L) Modulate Macrophage Function in a Model of Age-Related Macular Degeneration

    PubMed Central

    Zhao, Hui; Roychoudhury, Jayeeta; Doggett, Teresa A.; Apte, Rajendra S.; Ferguson, Thomas A.

    2013-01-01

    Purpose. We examined the effect of aging on Fas ligand (FasL) function in a mouse model of choroidal neovascularization (CNV). Methods. Young and aged mice were laser treated to induce CNV. Bone marrow chimeras were performed between young and aged mice. FasL protein expression was examined in the eye and soluble FasL (sFasL) was measured in the blood. Young and aged mice were treated with a matrix metalloprotease (MMP) inhibitor and systemic sFasL was neutralized by antibody treatment. Macrophages from young and aged mice were tested for sFasL-mediated cytokine production and migration. Results. The elevated CNV response observed with aging was dependent on bone marrow–derived cells. FasL expression in the eye was increased with age, but decreased following laser treatment. Aged mice had higher levels of sFasL in the blood compared to young mice. Systemic treatment with an MMP inhibitor decreased bloodborne sFasL, and reduced CNV in young and aged mice. Systemic neutralization of sFasL reduced CNV only in aged mice. sFasL increased cytokine production in aged macrophages and proangiogenic M2 macrophages. Aged M2 macrophages had elevated Fas (CD95) expression and displayed increased migration in response to sFasL compared to M1 macrophages derived from young animals. Conclusions. Age modulates FasL function where increased MMP cleavage leads to a loss of function in the eye. The released form of FasL (sFasL) preferentially induces the migration of proangiogenic M2 macrophages into the laser lesions and increases proangiogenic cytokines promoting CNV. FasL may be a viable target for therapeutic intervention in aged-related neovascular disease. PMID:23821188

  16. Age estimation based on pelvic ossification using regression models from conventional radiography.

    PubMed

    Zhang, Kui; Dong, Xiao-Ai; Fan, Fei; Deng, Zhen-Hua

    2016-07-01

    To establish regression models for age estimation from the combination of the ossification of iliac crest and ischial tuberosity. One thousand three hundred and seventy-nine conventional pelvic radiographs at the West China Hospital of Sichuan University between January 2010 and June 2012 were evaluated retrospectively. The receiver operating characteristic analysis was performed to measure the value of estimation of 18 years of age with the classification scheme for the iliac crest and ischial tuberosity. Regression analysis was performed, and formulas for calculating approximate chronological age according to the combination developmental status of the ossification for the iliac crest and ischial tuberosity were developed. The areas under the receiver operating characteristic (ROC) curves were above 0.9 (p < 0.001), indicating a good prediction of the grading systems, and the cubic regression model was found to have the highest R-square value (R (2) = 0.744 for female and R (2) = 0.753 for male). The present classification scheme for apophyseal iliac crest ossification and the ischial tuberosity may be used for age estimation. And the present established cubic regression model according to the combination developmental status of the ossification for the iliac crest and ischial tuberosity can be used for age estimation. PMID:27169673

  17. Active Aging for Individuals with Parkinson's Disease: Definitions, Literature Review, and Models

    PubMed Central

    Lökk, Johan

    2014-01-01

    Active aging has been emerged to optimize different aspects of health opportunities during the aging process in order to enhance quality of life. Yet, most of the efforts are on normal aging and less attention has been paid for the elderly suffering from a chronic illness such as Parkinson's disease (PD). The aim of this review was to investigate how the concept of “active aging” fit for the elderly with PD and to propose a new model for them using the recent improvements in caring models and management approaches. For this purpose, biomedical databases have been assessed using relevant keywords to find out appropriate articles. Movement problems of PD affect physical activity, psychiatric symptoms lessen social communication, and cognitive impairment could worsen mental well-being in elderly with PD, all of which could lead to earlier retirement and poorer quality of life compared with healthy elderly. Based on the multisystematic nature of PD, a new “Active Aging Model for Parkinson's Disease” is proposed consisting of self-care, multidisciplinary and interdisciplinary care, palliative care, patient-centered care, and personalized care. These strategies could potentially help the individuals with PD to have a better management approach for their condition towards the concept of active aging. PMID:25225618

  18. A Validated Normative Model for Human Uterine Volume from Birth to Age 40 Years

    PubMed Central

    Ginbey, Eleanor; Chowdhury, Moti M.; Bath, Louise E.; Anderson, Richard A.; Wallace, W. Hamish B.

    2016-01-01

    Transabdominal pelvic ultrasound and/or pelvic Magnetic Resonance Imaging are safe, accurate and non-invasive means of determining the size and configuration of the internal female genitalia. The assessment of uterine size and volume is helpful in the assessment of many conditions including disorders of sex development, precocious or delayed puberty, infertility and menstrual disorders. Using our own data from the assessment of MRI scans in healthy young females and data extracted from four studies that assessed uterine volume using transabdominal ultrasound in healthy females we have derived and validated a normative model of uterine volume from birth to age 40 years. This shows that uterine volume increases across childhood, with a faster increase in adolescence reflecting the influence of puberty, followed by a slow but progressive rise during adult life. The model suggests that around 84% of the variation in uterine volumes in the healthy population up to age 40 is due to age alone. The derivation of a validated normative model for uterine volume from birth to age 40 years has important clinical applications by providing age-related reference values for uterine volume. PMID:27295032

  19. Experimental characterization and modeling of isothermal and nonisothermal physical aging in glassy polymer films

    NASA Astrophysics Data System (ADS)

    Guo, Yunlong

    This dissertation focuses on nonisothermal physical aging of polymers from both experimental and theoretical aspects. The study concentrates on pure polymers rather than fiber-reinforced composites; this step removes several complicating factors to simplify the study. It is anticipated that the findings of this work can then be applied to composite materials applications. The physical aging tests in this work are performed using a dynamic mechanical analyzer (DMA). The viscoelastic response of glassy polymers under various loading and thermal histories are observed as stress-strain data at a series of time points. The first stage of the experimental work involves the characterization of the isothermal physical aging behavior of two advanced thermoplastics. The second stage conducts tests on the same materials with varying thermal histories and with long-term test duration. This forms the basis to assess and modify a nonisothermal physical aging model (KAHR-ate model). Based on the experimental findings, the KAHR-ate model has been revised by new correlations between aging shift factors and volume response; this revised model performed well in predicting the nonisothermal physical aging behavior of glassy polymers. In the work on isothermal physical aging, short-term creep and stress relaxation tests were performed at several temperatures within 15-35°C below the glass transition temperature (Tg) at various aging times, using the short-term test method established by Struik. Stress and strain levels were such that the materials remained in the linear viscoelastic regime. These curves were then shifted together to determine momentary master curves and shift rates. In order to validate the obtained isothermal physical aging behavior, the results of creep and stress relaxation testing were compared and shown to be consistent with one another using appropriate interconversion of the viscoelastic material functions. Time-temperature superposition of the master curves

  20. Structured additive regression modeling of age of menarche and menopause in a breast cancer screening program.

    PubMed

    Duarte, Elisa; de Sousa, Bruno; Cadarso-Suarez, Carmen; Rodrigues, Vitor; Kneib, Thomas

    2014-05-01

    Breast cancer risk is believed to be associated with several reproductive factors, such as early menarche and late menopause. This study is based on the registries of the first time a woman enters the screening program, and presents a spatio-temporal analysis of the variables age of menarche and age of menopause along with other reproductive and socioeconomic factors. The database was provided by the Portuguese Cancer League (LPCC), a private nonprofit organization dealing with multiple issues related to oncology of which the Breast Cancer Screening Program is one of its main activities. The registry consists of 259,652 records of women who entered the screening program for the first time between 1990 and 2007 (45-69-year age group). Structured Additive Regression (STAR) models were used to explore spatial and temporal correlations with a wide range of covariates. These models are flexible enough to deal with a variety of complex datasets, allowing us to reveal possible relationships among the variables considered in this study. The analysis shows that early menarche occurs in younger women and in municipalities located in the interior of central Portugal. Women living in inland municipalities register later ages for menopause, and those born in central Portugal after 1933 show a decreasing trend in the age of menopause. Younger ages of menarche and late menopause are observed in municipalities with a higher purchasing power index. The analysis performed in this study portrays the time evolution of the age of menarche and age of menopause and their spatial characterization, adding to the identification of factors that could be of the utmost importance in future breast cancer incidence research. PMID:24615881

  1. The Penna model for biological ageing on a lattice: spatial consequences of child-care

    NASA Astrophysics Data System (ADS)

    Sousa, A. O.; Moss de Oliveira, S.

    We introduce a square lattice into the Penna bit-string model for biological ageing and study the evolution of the spatial distribution of the population considering different strategies of child-care. Two of the strategies are related to the movements of a whole family on the lattice: in one case the mother cannot move if she has any child younger than a given age, and in the other case if she moves, she brings these young children with her. A stronger condition has also been added to the second case, considering that young children die with a higher probability if their mothers die, this probability decreasing with age. We show that a highly non uniform occupation can be obtained when child-care is considered, even for an uniform initial occupation per site. We also compare the standard survival rate of the model with that obtained when the spacial lattice is considered (without any kind of child-care).

  2. The age-metallicity-velocity dispersion relation in the solar neighborhood and a simple evolution model

    NASA Astrophysics Data System (ADS)

    Meusinger, H.; Stecklum, B.; Reimann, H.-G.

    1991-05-01

    An analysis of the age-metallicity relation (AMR) based on previous data is conducted again and the age-velocity relation (AVR) is estimated for some nearby stars to examine connections between the relations. In the period of evolution of the galactic disk, an important relationship with age is determined for both AMR and AVR. The observed metallicity-velocity relation is compared to the predicted relation to verify the AVR and AMR derivations. A model is presented in which the star formation rate, the infall rate of gas, and the initial mass function are constant. The model is found to agree with observed constraints on star counts in the solar neighborhood and constraints on the chemical and kinematical evolution of the local disk. A theory regarding the primary heating mechanism of the galactic disk is developed in terms of the AVR, and possible explanations - massive gas clouds and transient spiral waves - are discussed.

  3. Arterial pulse pressure amplification described by means of a nonlinear wave model: characterization of human aging

    NASA Astrophysics Data System (ADS)

    Alfonso, M.; Cymberknop, L.; Armentano, R.; Pessana, F.; Wray, S.; Legnani, W.

    2016-04-01

    The representation of blood pressure pulse as a combination of solitons captures many of the phenomena observed during its propagation along the systemic circulation. The aim of this work is to analyze the applicability of a compartmental model for propagation regarding the pressure pulse amplification associated with arterial aging. The model was applied to blood pressure waveforms that were synthesized using solitons, and then validated by waveforms obtained from individuals from differentiated age groups. Morphological changes were verified in the blood pressure waveform as a consequence of the aging process (i.e. due to the increase in arterial stiffness). These changes are the result of both a nonlinear interaction and the phenomena present in the propagation of nonlinear mechanic waves.

  4. Age at First Birth and Fathers' Subsequent Health: Evidence From Sibling and Twin Models

    PubMed Central

    Pudrovska, Tetyana; Carr, Deborah

    2010-01-01

    Using a sample of 540 siblings and twins from the National Survey of Midlife Development in the United States, this study examines the relationship between the age at which men become biological fathers and their subsequent health. The analysis includes both between-family models that treat brothers as independent observations and within-family models that account for unobserved genetic and early-life environmental endowments shared by brothers within families. Findings indicate that age at first birth has a positive, linear effect on men's health, and this relationship is not explained by the confounding influences of unobserved early-life characteristics. However, the effect of age at first birth on fathers' health is explained by men's socioeconomic and family statuses. Whereas most research linking birth timing to specific diseases focuses narrowly on biological mechanisms among mothers, this study demonstrates the importance of reproductive decisions for men's health and well-being. PMID:19477723

  5. Neuroscientists as Cartographers: Mapping the Crossroads of Gonadal Hormones, Memory and Age Using Animal Models

    PubMed Central

    Bimonte-Nelson, Heather A.; Acosta, Jazmin I.; Talboom, Joshua S.

    2010-01-01

    Cognitive function is multidimensional and complex, and research in multiple species indicates it is considerably impacted by age and gonadal hormone milieu. One domain of cognitive function particularly susceptible to age-related decrements is spatial memory. Gonadal hormones can alter spatial memory, and they are potent modulators of brain microstructure and function in many of the same brain areas affected by aging. In this paper, we review decades of animal and human literature to support a tertiary model representing interactions between gonadal hormones, spatial cognition and age given that: 1) gonadal hormones change with age, 2) age impacts spatial learning and memory, and 3) gonadal hormones impact spatial learning and memory. While much has been discovered regarding these individual tenets, the compass for future aging research points toward clarifying the interactions that exist between these three points, and understanding mediating variables. Indeed, identifying and aligning the various components of the complex interactions between these tenets, including evaluations using basic science, systems, and clinical perspectives, is the optimal approach to attempt to converge the many findings that may currently appear contradictory. In fact, as discoveries are being made it is becoming clear that the findings across studies that appear contradictory are not contradictory at all. Rather, there are mediating variables that are influencing outcome and affecting the extent, and even the direction, of the effects that gonadal hormones have on cognition during aging. These mediating variables are just starting to be understood. By aligning basic scientific discoveries with clinical interpretations, we can maximize the opportunities for discoveries and subsequent interventions to allow individuals to “optimize their aging” and find their own map to cognitive health as aging ensues. PMID:20877209

  6. The hierarchical factor model of ADHD: Invariant across age and national groupings?

    PubMed Central

    Toplak, Maggie E.; Sorge, Geoff B.; Flora, David B.; Chen, Wai; Banaschewski, Tobias; Buitelaar, Jan; Ebstein, Richard; Eisenberg, Jacques; Franke, Barbara; Gill, Michael; Miranda, Ana; Oades, Robert D.; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph; Sonuga-Barke, Edmund; Steinhausen, Hans-Christoph; Thompson, Margaret; Tannock, Rosemary; Asherson, Philip; Faraone, Stephen V.

    2011-01-01

    Objective To examine the factor structure of Attention-Deficit/Hyperactivity Disorder (ADHD) in a clinical sample of 1373 children and adolescents with ADHD and their 1772 unselected siblings recruited from different countries across a large age range. Hierarchical and correlated factor analytic models were compared separately in the ADHD and sibling samples, across three different instruments and across parent and teacher informants. Specific consideration was given to factorial invariance analyses across different ages and different countries in the ADHD sample. Method A sample of children and adolescents between 5 and 17 years of age with ADHD and their unselected siblings was assessed. Participants were recruited from seven European countries and Israel. ADHD symptom data came from a clinical interview with parents (PACS) and questionnaires from parents and teachers (Conners Parent and Teacher). Results A hierarchical general factor model with two specific factors best represented the structure of ADHD in both the ADHD and unselected sibling groups, and across informants and instruments. The model was robust and invariant with regard to age differences in the ADHD sample. The model was not strongly invariant across different national groups in the ADHD sample, likely reflecting severity differences across the different centers and not any substantial difference in the clinical presentation of ADHD. Conclusions The results replicate previous studies of a model with a unitary ADHD component and separable specific traits of inattention and hyperactivity/impulsivity. The unique contribution of this study was finding support for this model across a large developmental and multinational/multicultural sample and its invariance across ages. PMID:22084976

  7. Compact modeling of total ionizing dose and aging effects in MOS technologies

    DOE PAGESBeta

    Esqueda, Ivan S.; Barnaby, Hugh J.; King, Michael Patrick

    2015-06-18

    This paper presents a physics-based compact modeling approach that incorporates the impact of total ionizing dose (TID) and stress-induced defects into simulations of metal-oxide-semiconductor (MOS) devices and integrated circuits (ICs). This approach utilizes calculations of surface potential (ψs) to capture the charge contribution from oxide trapped charge and interface traps and to describe their impact on MOS electrostatics and device operating characteristics as a function of ionizing radiation exposure and aging effects. The modeling approach is demonstrated for bulk and silicon-on-insulator (SOI) MOS device. The formulation is verified using TCAD simulations and through the comparison of model calculations and experimentalmore » I-V characteristics from irradiated devices. The presented approach is suitable for modeling TID and aging effects in advanced MOS devices and ICs.« less

  8. Compact modeling of total ionizing dose and aging effects in MOS technologies

    SciTech Connect

    Esqueda, Ivan S.; Barnaby, Hugh J.; King, Michael Patrick

    2015-06-18

    This paper presents a physics-based compact modeling approach that incorporates the impact of total ionizing dose (TID) and stress-induced defects into simulations of metal-oxide-semiconductor (MOS) devices and integrated circuits (ICs). This approach utilizes calculations of surface potential (ψs) to capture the charge contribution from oxide trapped charge and interface traps and to describe their impact on MOS electrostatics and device operating characteristics as a function of ionizing radiation exposure and aging effects. The modeling approach is demonstrated for bulk and silicon-on-insulator (SOI) MOS device. The formulation is verified using TCAD simulations and through the comparison of model calculations and experimental I-V characteristics from irradiated devices. The presented approach is suitable for modeling TID and aging effects in advanced MOS devices and ICs.

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

    PubMed

    Mohiuddin, Mohammad W; Rihani, Ryan J; Laine, Glen A; Quick, Christopher M

    2012-07-01

    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 (C(tot)) and increases in total peripheral resistance (R(tot)) with age. Investigators assuming a more sophisticated pulse transmission model believe PP rises because increases in pulse wave velocity (c(ph)) make the reflected pressure wave arrive earlier, augmenting systolic pressure. It has recently been shown, however, that increases in c(ph) 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 c(ph) cause increased PP with age. First, we made the realistic arterial system model age dependent by altering cardiac output (CO), R(tot), C(tot), and c(ph) to mimic the reported changes in these parameters from age 30 to 70. Then, c(ph) was theoretically maintained constant, while C(tot), R(tot), and CO were altered. The predicted increase in PP with age was similar to the observed increase in PP. In a complementary approach, C(tot), R(tot), and CO were theoretically maintained constant, and c(ph) was increased. The predicted increase in PP was negligible. We found that increases in c(ph) 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 C(tot). PMID:22561301

  10. Cyclostratigraphy for Chinese red clay sequences: Implications to changing previous age models and paleoclimate interpretations

    NASA Astrophysics Data System (ADS)

    Anwar, T.; Kravchinsky, V. A.; Zhang, R.

    2015-12-01

    The Chinese Loess Plateau contains red clay sequence which has continuous alternation of sedimentary cycles with recurrent paleoclimatic fluctuations. Absence of abundant fossils and inability of radiometric dating method made magnetostratigraphy a leading method to build age model for the red clay. Here magnetostratigraphic age model in red clay sequence is tested using cyclostratigraphy as orbital parameters of Earth are known. Milankovitch periodicities recorded in magnetic susceptibility and grain size in the Shilou red clay section are investigated and previously found age of 11 Ma for this section is re-evaluated. Magnetostratigraphy dating based on only visual correlation could potentially lead to erroneous age model. In this study the correlation is executed through the iteration procedure until it is supported by cyclostratigraphy; i.e. Milankovitch cycles are resolved in the best possible manner. Our new approach provides an age of 5.2 Ma for the Shilou profile. Wavelet analysis reveals that a 400 kyr eccentricity cycle is well preserved and the existence of a 100 kyr eccentricity in the red clay sequence on the eastern Chinese Loess Plateau suggests that eccentricity plays a vital role in Pliocene climate evolution. Paleomonsoon evolution is reconstructed and divided into three intervals (5.2-4.5 Ma, 4.5-3.6 Ma and 3.6-2.58 Ma). The earliest stage indicates that summer and winter monsoon cycles may rapidly alter, whereas the middle stage reflects an intensification of winter monsoon and aridification in Asia, and the youngest stage is characterized by relatively intensified summer monsoon. This study demonstrates that cyclostratigraphy can greatly assist magnetostratigraphy in dating the red clay sequences, and implies that many published age models for the red clay sequences should likely be re-assessed where possible. An evaluation of the monsoon system and climate change in eastern Asia might prominently benefit from this approach.

  11. Effects of Exendin-4 on Male Reproductive Parameters of D-Galactose Induced Aging Mouse Model

    PubMed Central

    Ahangarpour, Akram; Heidari, Hamid

    2014-01-01

    Purpose The purpose of this study was to evaluate the role of exendin-4 on reproductive alteration in a D-galactose-induced aging mouse model. Materials and Methods In this experimental study, 72 male Naval Medical Research Institute mice (20~25 g) were randomly divided into six groups: control, exendin-4 (1 nmol/kg), exendin-4 (10 nmol/kg), D-galactose (500 mg/kg), D-galactose+exendin-4 (1 nmol/kg), and D-galactose+exendin-4 (10 nmol/kg). The aging model animals were gavaged with D-galactose for six weeks, and exendin-4 was injected intraperitoneally in the last 10 days. At the end of treatment serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone levels were evaluated and the cauda epididymis and testis were removed to analyze the sperm count and testis morphology. Results The testis weight and volume decreased in the D-galactose group (p<0.01 and p<0.05) respectively. Exendin-4 (1, 10 nmol/kg) increased these parameters in the normal and aging mouse models. Serum LH and FSH levels increased and the sperm count decreased in the D-galactose group (p<0.05). Further, exendin-4 (1 nmol/kg) decreased LH and FSH levels and increased the serum testosterone level and sperm count in both normal and aging animals. Conclusions D-galactose can induce aging alternations in the male reproductive system such as decreased sperm count and increased serum LH and FSH levels through reactive oxygen species over production and reduced antioxidant enzyme activity. Further, co-administration of exendin-4 reduced reproductive complications of D-galactose in an aging mouse model. PMID:25606567

  12. Model Fitting Versus Curve Fitting: A Model of Renormalization Provides a Better Account of Age Aftereffects Than a Model of Local Repulsion

    PubMed Central

    Mac, Amy; Rhodes, Gillian; Webster, Michael A.

    2015-01-01

    Recently, we proposed that the aftereffects of adapting to facial age are consistent with a renormalization of the perceived age (e.g., so that after adapting to a younger or older age, all ages appear slightly older or younger, respectively). This conclusion has been challenged by arguing that the aftereffects can also be accounted for by an alternative model based on repulsion (in which facial ages above or below the adapting age are biased away from the adaptor). However, we show here that this challenge was based on allowing the fitted functions to take on values which are implausible and incompatible across the different adapting conditions. When the fits are constrained or interpreted in terms of standard assumptions about normalization and repulsion, then the two analyses both agree in pointing to a pattern of renormalization in age aftereffects. PMID:27551353

  13. Improvement, Supervision, and Dissemination of a Model Cross-Age Tutoring Program.

    ERIC Educational Resources Information Center

    Breedlove, Donnie L.

    This practicum was developed (1) to improve, supervise, and disseminate a model cross-age tutoring program, and (2) to determine if a tutorial program would increase the sight vocabulary of 100 second grade students in the Dallas Independent School District. A secondary purpose was to determine if such a program would improve the reading grades,…

  14. The Hierarchical Factor Model of ADHD: Invariant across Age and National Groupings?

    ERIC Educational Resources Information Center

    Toplak, Maggie E.; Sorge, Geoff B.; Flora, David B.; Chen, Wai; Banaschewski, Tobias; Buitelaar, Jan; Ebstein, Richard; Eisenberg, Jacques; Franke, Barbara; Gill, Michael; Miranda, Ana; Oades, Robert D.; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph; Sonuga-Barke, Edmund; Steinhausen, Hans-Christoph; Thompson, Margaret; Tannock, Rosemary; Asherson, Philip; Faraone, Stephen V.

    2012-01-01

    Objective: To examine the factor structure of attention-deficit/hyperactivity disorder (ADHD) in a clinical sample of 1,373 children and adolescents with ADHD and their 1,772 unselected siblings recruited from different countries across a large age range. Hierarchical and correlated factor analytic models were compared separately in the ADHD and…

  15. The reemergence of long-term potentiation in aged Alzheimer’s disease mouse model

    PubMed Central

    Huh, Seonghoo; Baek, Soo-Ji; Lee, Kyung-Hwa; Whitcomb, Daniel J.; Jo, Jihoon; Choi, Seong-Min; Kim, Dong Hyun; Park, Man-Seok; Lee, Kun Ho; Kim, Byeong C.

    2016-01-01

    Mouse models of Alzheimer’s disease (AD) have been developed to study the pathophysiology of amyloid β protein (Aβ) toxicity, which is thought to cause severe clinical symptoms such as memory impairment in AD patients. However, inconsistencies exist between studies using these animal models, specifically in terms of the effects on synaptic plasticity, a major cellular model of learning and memory. Whereas some studies find impairments in plasticity in these models, others do not. We show that long-term potentiation (LTP), in the CA1 region of hippocampal slices from this mouse, is impared at Tg2576 adult 6–7 months old. However, LTP is inducible again in slices taken from Tg2576 aged 14–19 months old. In the aged Tg2576, we found that the percentage of parvalbumin (PV)-expressing interneurons in hippocampal CA1-3 region is significantly decreased, and LTP inhibition or reversal mediated by NRG1/ErbB signaling, which requires ErbB4 receptors in PV interneurons, is impaired. Inhibition of ErbB receptor kinase in adult Tg2576 restores LTP but impairs depotentiation as shown in aged Tg2576. Our study suggests that hippocampal LTP reemerges in aged Tg2576. However, this reemerged LTP is an insuppressible form due to impaired NRG1/ErbB signaling, possibly through the loss of PV interneurons. PMID:27377368

  16. The reemergence of long-term potentiation in aged Alzheimer's disease mouse model.

    PubMed

    Huh, Seonghoo; Baek, Soo-Ji; Lee, Kyung-Hwa; Whitcomb, Daniel J; Jo, Jihoon; Choi, Seong-Min; Kim, Dong Hyun; Park, Man-Seok; Lee, Kun Ho; Kim, Byeong C

    2016-01-01

    Mouse models of Alzheimer's disease (AD) have been developed to study the pathophysiology of amyloid β protein (Aβ) toxicity, which is thought to cause severe clinical symptoms such as memory impairment in AD patients. However, inconsistencies exist between studies using these animal models, specifically in terms of the effects on synaptic plasticity, a major cellular model of learning and memory. Whereas some studies find impairments in plasticity in these models, others do not. We show that long-term potentiation (LTP), in the CA1 region of hippocampal slices from this mouse, is impared at Tg2576 adult 6-7 months old. However, LTP is inducible again in slices taken from Tg2576 aged 14-19 months old. In the aged Tg2576, we found that the percentage of parvalbumin (PV)-expressing interneurons in hippocampal CA1-3 region is significantly decreased, and LTP inhibition or reversal mediated by NRG1/ErbB signaling, which requires ErbB4 receptors in PV interneurons, is impaired. Inhibition of ErbB receptor kinase in adult Tg2576 restores LTP but impairs depotentiation as shown in aged Tg2576. Our study suggests that hippocampal LTP reemerges in aged Tg2576. However, this reemerged LTP is an insuppressible form due to impaired NRG1/ErbB signaling, possibly through the loss of PV interneurons. PMID:27377368

  17. The "Village" Model: A Consumer-Driven Approach for Aging in Place

    ERIC Educational Resources Information Center

    Scharlach, Andrew; Graham, Carrie; Lehning, Amanda

    2012-01-01

    Purpose of the Study: This study examines the characteristics of the "Village" model, an innovative consumer-driven approach that aims to promote aging in place through a combination of member supports, service referrals, and consumer engagement. Design and Methods: Thirty of 42 fully operational Villages completed 2 surveys. One survey examined…

  18. HUMAN SUBJECT AGE AND ACTIVITY LEVEL: FACTORS ADDRESSED IN A BIOMATHEMATICAL DEPOSITION PROGRAM FOR EXTRAPOLATION MODELING

    EPA Science Inventory

    A deterministic aerosol deposition model, previously validated by data from adult inhalation exposure experiments, is used to study factors affecting particle behavior within the developing human lung. ere, an age dependent lung morphology is presented in which the number of trac...

  19. AGE DEPENDENT MODEL OF PCB IN A LAKE MICHIGAN FOOD CHAIN

    EPA Science Inventory

    An age-dependent food chain model that considers species bioenergetics and toxicant exposure through water and food was developed. It was successfully applied to PCB contamination in the Lake Michigan lake trout food chain represented by phytoplankton, Mysis, alewife, and lake tr...

  20. The Source of Adult Age Differences in Event-Based Prospective Memory: A Multinomial Modeling Approach

    ERIC Educational Resources Information Center

    Smith, Rebekah E.; Bayen, Ute J.

    2006-01-01

    Event-based prospective memory involves remembering to perform an action in response to a particular future event. Normal younger and older adults performed event-based prospective memory tasks in 2 experiments. The authors applied a formal multinomial processing tree model of prospective memory (Smith & Bayen, 2004) to disentangle age differences…

  1. All-Ages Lead Model (Aalm) Version 1.05 (External Draft Report)

    EPA Science Inventory

    The All-Ages Lead Model (AALM) Version 1.05, is an external review draft software and guidance manual. EPA released this software and associated documentation for public review and comment beginning September 27, 2005, until October 27, 2005. The public comments will be accepte...

  2. Aging in Place vs. Relocation for Older Adults with Neurocognitive Disorder: Applications of Wiseman's Behavioral Model.

    PubMed

    Kaplan, Daniel B; Andersen, Troy Christian; Lehning, Amanda J; Perry, Tam E

    2015-01-01

    Some older adults are more vulnerable to housing concerns due to physical and cognitive challenges, including those with a neurocognitive disorder who need extensive support. Environmental gerontology frameworks, including Wiseman's 1980 Behavioral Model of Elderly Migration, have informed scholarship on aging in place and relocation. Understanding Wiseman's model, including considerations for working with families confronting a neurocognitive disorder, can help practitioners ensure that older clients live in settings that best meet their wants and needs. PMID:26016530

  3. Aging Well Socially through Engagement with Life: Adapting Rowe and Kahn's Model of Successful Aging to Chinese Cultural Context

    ERIC Educational Resources Information Center

    Ng, Sik Hung; Cheung, Chau-Kiu; Chong, Alice M. L.; Woo, Jean; Kwan, Alex Y. H.; Lai, Stephanie

    2011-01-01

    Although aging well socially (Engagement with Life) is as important as aging well personally (Illness Avoidance and Functioning) (Rowe & Kahn, 1998), it has received less research attention. A Caring (CE) and a Productive (PE) form of Engagement were derived from an analysis of Chinese cultural meanings of engagement, and combined with Illness…

  4. Multi-State Physics Models of Aging Passive Components in Probabilistic Risk Assessment

    SciTech Connect

    Unwin, Stephen D.; Lowry, Peter P.; Layton, Robert F.; Heasler, Patrick G.; Toloczko, Mychailo B.

    2011-03-13

    Multi-state Markov modeling has proved to be a promising approach to estimating the reliability of passive components - particularly metallic pipe components - in the context of probabilistic risk assessment (PRA). These models consider the progressive degradation of a component through a series of observable discrete states, such as detectable flaw, leak and rupture. Service data then generally provides the basis for estimating the state transition rates. Research in materials science is producing a growing understanding of the physical phenomena that govern the aging degradation of passive pipe components. As a result, there is an emerging opportunity to incorporate these insights into PRA. This paper describes research conducted under the Risk-Informed Safety Margin Characterization Pathway of the Department of Energy’s Light Water Reactor Sustainability Program. A state transition model is described that addresses aging behavior associated with stress corrosion cracking in ASME Class 1 dissimilar metal welds – a component type relevant to LOCA analysis. The state transition rate estimates are based on physics models of weld degradation rather than service data. The resultant model is found to be non-Markov in that the transition rates are time-inhomogeneous and stochastic. Numerical solutions to the model provide insight into the effect of aging on component reliability.

  5. A statistical model for the study of U-Nb aging (u)

    SciTech Connect

    Hemphill, Geralyn M; Hackenberg, Robert E

    2009-01-01

    This study was undertaken to model the aging response of U-Nb alloys in order to quantify property and lifetime predictions and uncertainties, in response to concerns that aging during long-term stockpile storage may change the microstructure and properties of U-6 wt%Nb alloy components in ways adversely affecting performance. U-6Nb has many desirable properties, but is a complex material because of its gross compositional inhomogeneity (its chemical banding spans 4-8 wt%), its metastable starting microstructure, and the fact that a variety of external factors such as temperature, stress, and gaseous species can cause aging through multiple mechanisms. The most significant aging mechanism identified in earlier studies [2007hac2] is age hardening, phenomenologically defined as increasing hardness and strength and decreasing ductility observed as a function of increasing aging time-at-temperature. The scientific fundamentals of age hardening at temperatures relevant to U-6Nb material processing ({le}200 C) and stockpile storage ({le}60 C) remain unresolved in spite of significant experimental efforts [2007hac2, 2009cla]. Equally problematic is the lack of a well-established U-6Nb component failure criterion. These limitations make the most desirable approach of property response and lifetime prediction - that based on fundamental physics - unattainable at the present time. Therefore, a semi-empirical approach was taken to model the phenomenological property evolution during aging. This enabled lifetime estimates to be made from an assumed failure criterion (derived from a manufacturing acceptance criterion) couched in terms of an age-sensitive property, namely quasi-static tensile elongation to failure. The predictions of this and other age-sensitive properties are also useful for U-6Nb component surveillance studies. Drawing upon a large body of artificial aging data obtained from nonbanded (chemically homogeneous) U-5.6Nb and U-7.7Nb material [2007hacJ ] over 100

  6. Social Models of Aging [and] Modeles Sociaux du Vieillissement: Le Parcours de Vie, un Passage oblige? [and] Rejoinder to Haldemann.

    ERIC Educational Resources Information Center

    Marshall, Victor W.; Haldemann, Verena

    1995-01-01

    Marshall reviews four types of social models of aging: allocation, construction of life course, personality and socialization, and negotiation, concluding that the life course perspective dominates. Haldemann comments (in French) that broader research is needed to question this dominance; Marshall responds that his goal was to describe, not to…

  7. Quality Saving Mechanisms of Mitochondria during Aging in a Fully Time-Dependent Computational Biophysical Model.

    PubMed

    Mellem, Daniel; Fischer, Frank; Jaspers, Sören; Wenck, Horst; Rübhausen, Michael

    2016-01-01

    Mitochondria are essential for the energy production of eukaryotic cells. During aging mitochondria run through various processes which change their quality in terms of activity, health and metabolic supply. In recent years, many of these processes such as fission and fusion of mitochondria, mitophagy, mitochondrial biogenesis and energy consumption have been subject of research. Based on numerous experimental insights, it was possible to qualify mitochondrial behaviour in computational simulations. Here, we present a new biophysical model based on the approach of Figge et al. in 2012. We introduce exponential decay and growth laws for each mitochondrial process to derive its time-dependent probability during the aging of cells. All mitochondrial processes of the original model are mathematically and biophysically redefined and additional processes are implemented: Mitochondrial fission and fusion is separated into a metabolic outer-membrane part and a protein-related inner-membrane part, a quality-dependent threshold for mitophagy and mitochondrial biogenesis is introduced and processes for activity-dependent internal oxidative stress as well as mitochondrial repair mechanisms are newly included. Our findings reveal a decrease of mitochondrial quality and a fragmentation of the mitochondrial network during aging. Additionally, the model discloses a quality increasing mechanism due to the interplay of the mitophagy and biogenesis cycle and the fission and fusion cycle of mitochondria. It is revealed that decreased mitochondrial repair can be a quality saving process in aged cells. Furthermore, the model finds strategies to sustain the quality of the mitochondrial network in cells with high production rates of reactive oxygen species due to large energy demands. Hence, the model adds new insights to biophysical mechanisms of mitochondrial aging and provides novel understandings of the interdependency of mitochondrial processes. PMID:26771181

  8. Quality Saving Mechanisms of Mitochondria during Aging in a Fully Time-Dependent Computational Biophysical Model

    PubMed Central

    Mellem, Daniel; Fischer, Frank; Jaspers, Sören; Wenck, Horst; Rübhausen, Michael

    2016-01-01

    Mitochondria are essential for the energy production of eukaryotic cells. During aging mitochondria run through various processes which change their quality in terms of activity, health and metabolic supply. In recent years, many of these processes such as fission and fusion of mitochondria, mitophagy, mitochondrial biogenesis and energy consumption have been subject of research. Based on numerous experimental insights, it was possible to qualify mitochondrial behaviour in computational simulations. Here, we present a new biophysical model based on the approach of Figge et al. in 2012. We introduce exponential decay and growth laws for each mitochondrial process to derive its time-dependent probability during the aging of cells. All mitochondrial processes of the original model are mathematically and biophysically redefined and additional processes are implemented: Mitochondrial fission and fusion is separated into a metabolic outer-membrane part and a protein-related inner-membrane part, a quality-dependent threshold for mitophagy and mitochondrial biogenesis is introduced and processes for activity-dependent internal oxidative stress as well as mitochondrial repair mechanisms are newly included. Our findings reveal a decrease of mitochondrial quality and a fragmentation of the mitochondrial network during aging. Additionally, the model discloses a quality increasing mechanism due to the interplay of the mitophagy and biogenesis cycle and the fission and fusion cycle of mitochondria. It is revealed that decreased mitochondrial repair can be a quality saving process in aged cells. Furthermore, the model finds strategies to sustain the quality of the mitochondrial network in cells with high production rates of reactive oxygen species due to large energy demands. Hence, the model adds new insights to biophysical mechanisms of mitochondrial aging and provides novel understandings of the interdependency of mitochondrial processes. PMID:26771181

  9. Novel gene function revealed by mouse mutagenesis screens for models of age-related disease

    PubMed Central

    Potter, Paul K.; Bowl, Michael R.; Jeyarajan, Prashanthini; Wisby, Laura; Blease, Andrew; Goldsworthy, Michelle E.; Simon, Michelle M.; Greenaway, Simon; Michel, Vincent; Barnard, Alun; Aguilar, Carlos; Agnew, Thomas; Banks, Gareth; Blake, Andrew; Chessum, Lauren; Dorning, Joanne; Falcone, Sara; Goosey, Laurence; Harris, Shelley; Haynes, Andy; Heise, Ines; Hillier, Rosie; Hough, Tertius; Hoslin, Angela; Hutchison, Marie; King, Ruairidh; Kumar, Saumya; Lad, Heena V.; Law, Gemma; MacLaren, Robert E.; Morse, Susan; Nicol, Thomas; Parker, Andrew; Pickford, Karen; Sethi, Siddharth; Starbuck, Becky; Stelma, Femke; Cheeseman, Michael; Cross, Sally H.; Foster, Russell G.; Jackson, Ian J.; Peirson, Stuart N.; Thakker, Rajesh V.; Vincent, Tonia; Scudamore, Cheryl; Wells, Sara; El-Amraoui, Aziz; Petit, Christine; Acevedo-Arozena, Abraham; Nolan, Patrick M.; Cox, Roger; Mallon, Anne-Marie; Brown, Steve D. M.

    2016-01-01

    Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss. PMID:27534441

  10. Modeled tephra ages from lake sediments, base of Redoubt Volcano, Alaska

    USGS Publications Warehouse

    Schiff, C.J.; Kaufman, D.S.; Wallace, K.L.; Werner, A.; Ku, T.-L.; Brown, T.A.

    2008-01-01

    A 5.6-m-long lake sediment core from Bear Lake, Alaska, located 22 km southeast of Redoubt Volcano, contains 67 tephra layers deposited over the last 8750 cal yr, comprising 15% of the total thickness of recovered sediment. Using 12 AMS 14C ages, along with the 137Cs and 210Pb activities of recent sediment, we evaluated different models to determine the age-depth relation of the core, and to determine the age of each tephra deposit. The selected age model is based on a mixed-effect regression that was passed through the adjusted tephra-free depth of each dated layer. The estimated age uncertainty of the 67 tephras averages ??105 yr (95% confidence intervals). Tephra-fall frequency at Bear Lake was among the highest during the past 500 yr, with eight tephras deposited compared to an average of 3.7/500 yr over the last 8500 yr. Other periods of increased tephra fall occurred 2500-3500, 4500-5000, and 7000-7500 cal yr. Our record suggests that Bear Lake experienced extended periods (1000-2000 yr) of increased tephra fall separated by shorter periods (500-1000 yr) of apparent quiescence. The Bear Lake sediment core affords the most comprehensive tephrochronology from the base of the Redoubt Volcano to date, with an average tephra-fall frequency of one every 130 yr. ?? 2007 Elsevier Ltd. All rights reserved.

  11. Modeled tephra ages from lake sediments, base of Redoubt Volcano, Alaska

    SciTech Connect

    Schiff, C J; Kaufman, D S; Wallace, K L; Werner, A; Ku, T L; Brown, T A

    2007-02-25

    A 5.6-m-long lake sediment core from Bear Lake, Alaska, located 22 km southeast of Redoubt Volcano, contains 67 tephra layers deposited over the last 8750 cal yr, comprising 15% of the total thickness of recovered sediment. Using 12 AMS {sup 14}C ages, along with the {sup 137}Cs and {sup 210}Pb activities of recent sediment, we evaluated different models to determine the age-depth relation of sediment, and to determine the age of each tephra deposit. The age model is based on a cubic smooth spline function that was passed through the adjusted tephra-free depth of each dated layer. The estimated age uncertainty of the 67 tephras averages {+-} 105 yr (1{sigma}). Tephra-fall frequency at Bear Lake was among the highest during the past 500 yr, with eight tephras deposited compared to an average of 3.7 per 500 yr over the last 8500 yr. Other periods of increased tephra fall occurred 2500-3500, 4500-5000, and 7000-7500 cal yr. Our record suggests that Bear Lake experienced extended periods (1000-2000 yr) of increased tephra fall separated by shorter periods (500-1000 yr) of apparent quiescence. The Bear Lake sediment core affords the most comprehensive tephrochronology from the base of the Redoubt Volcano to date, with an average tephra-fall frequency of once every 130 yr.

  12. Novel gene function revealed by mouse mutagenesis screens for models of age-related disease.

    PubMed

    Potter, Paul K; Bowl, Michael R; Jeyarajan, Prashanthini; Wisby, Laura; Blease, Andrew; Goldsworthy, Michelle E; Simon, Michelle M; Greenaway, Simon; Michel, Vincent; Barnard, Alun; Aguilar, Carlos; Agnew, Thomas; Banks, Gareth; Blake, Andrew; Chessum, Lauren; Dorning, Joanne; Falcone, Sara; Goosey, Laurence; Harris, Shelley; Haynes, Andy; Heise, Ines; Hillier, Rosie; Hough, Tertius; Hoslin, Angela; Hutchison, Marie; King, Ruairidh; Kumar, Saumya; Lad, Heena V; Law, Gemma; MacLaren, Robert E; Morse, Susan; Nicol, Thomas; Parker, Andrew; Pickford, Karen; Sethi, Siddharth; Starbuck, Becky; Stelma, Femke; Cheeseman, Michael; Cross, Sally H; Foster, Russell G; Jackson, Ian J; Peirson, Stuart N; Thakker, Rajesh V; Vincent, Tonia; Scudamore, Cheryl; Wells, Sara; El-Amraoui, Aziz; Petit, Christine; Acevedo-Arozena, Abraham; Nolan, Patrick M; Cox, Roger; Mallon, Anne-Marie; Brown, Steve D M

    2016-01-01

    Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss. PMID:27534441

  13. Stability analysis of a model gene network links aging, stress resistance, and negligible senescence.

    PubMed

    Kogan, Valeria; Molodtsov, Ivan; Menshikov, Leonid I; Shmookler Reis, Robert J; Fedichev, Peter

    2015-01-01

    Several animal species are considered to exhibit what is called negligible senescence, i.e. they do not show signs of functional decline or any increase of mortality with age. Recent studies in naked mole rat and long-lived sea urchins showed that these species do not alter their gene-expression profiles with age as much as other organisms do. This is consistent with exceptional endurance of naked mole rat tissues to various genotoxic stresses. We conjectured, therefore, that the lifelong transcriptional stability of an organism may be a key determinant of longevity. We analyzed the stability of a simple genetic-network model and found that under most common circumstances, such a gene network is inherently unstable. Over a time it undergoes an exponential accumulation of gene-regulation deviations leading to death. However, should the repair systems be sufficiently effective, the gene network can stabilize so that gene damage remains constrained along with mortality of the organism. We investigate the relationship between stress-resistance and aging and suggest that the unstable regime may provide a mathematical basis for the Gompertz "law" of aging in many species. At the same time, this model accounts for the apparently age-independent mortality observed in some exceptionally long-lived animals. PMID:26316217

  14. Stability analysis of a model gene network links aging, stress resistance, and negligible senescence

    PubMed Central

    Kogan, Valeria; Molodtsov, Ivan; Menshikov, Leonid I.; Reis, Robert J. Shmookler; Fedichev, Peter

    2015-01-01

    Several animal species are considered to exhibit what is called negligible senescence, i.e. they do not show signs of functional decline or any increase of mortality with age. Recent studies in naked mole rat and long-lived sea urchins showed that these species do not alter their gene-expression profiles with age as much as other organisms do. This is consistent with exceptional endurance of naked mole rat tissues to various genotoxic stresses. We conjectured, therefore, that the lifelong transcriptional stability of an organism may be a key determinant of longevity. We analyzed the stability of a simple genetic-network model and found that under most common circumstances, such a gene network is inherently unstable. Over a time it undergoes an exponential accumulation of gene-regulation deviations leading to death. However, should the repair systems be sufficiently effective, the gene network can stabilize so that gene damage remains constrained along with mortality of the organism. We investigate the relationship between stress-resistance and aging and suggest that the unstable regime may provide a mathematical basis for the Gompertz “law” of aging in many species. At the same time, this model accounts for the apparently age-independent mortality observed in some exceptionally long-lived animals. PMID:26316217

  15. Does the Village model help to foster age-friendly communities?

    PubMed

    Scharlach, Andrew E; Davitt, Joan K; Lehning, Amanda J; Greenfield, Emily A; Graham, Carrie L

    2014-01-01

    This article explores the potential role of the Village model, a social initiative that emphasizes member involvement and service access, in helping communities to become more age-friendly. A survey of 86.3% of operational Villages examined activities designed to help members access a variety of supports and services consistent with the World Health Organization's (WHO) Global Network of Age-Friendly Cities and Communities program model, as well as other potential contributions to community age friendliness. Analysis revealed that 85.5% of Villages provided assistance with at least six of the eight WHO domains, but only 10.1% implemented features of all eight; more than one-third were engaged in direct or indirect efforts to improve community physical or social infrastructures or improve community attitudes toward older persons. These findings suggest that Villages and other social organizations may have untapped potential for enhancing their members' ability to age in place consistent with the goals of age-friendly initiatives while also promoting constructive changes in the overall community. PMID:24224776

  16. Racial disparities in age at time of homicide victimization: a test of the multiple disadvantage model.

    PubMed

    Lo, Celia C; Howell, Rebecca J; Cheng, Tyrone C

    2015-01-01

    This study sought the factors associated with race/ethnicity disparities in the age at which homicide deaths tend to occur. We used the multiple disadvantage model to take race into account as we evaluated associations between age at time of homicide victimization and several social structural, mental health-related, and lifestyle factors. Data were derived from the 1993 National Mortality Followback Survey, a cross-sectional interview study of spouses, next of kin, other relatives, and close friends of individuals 15 years and older who died in the United States in 1993. Our results showed age at time of homicide mortality to be related to the three types of factors; race moderated some of these relationships. In general, being employed, married, and a homeowner appeared associated with reduced victimization while young. The relationship of victimization age and employment was not uniform across racial groups, nor was the relationship of victimization age and marital status uniform across groups. Among Blacks, using mental health services was associated with longer life. Homicide by firearm proved important for our Black and Hispanic subsamples, while among Whites, alcohol's involvement in homicide exerted significant effects. Our results suggest that programs and policies serving the various racial/ethnic groups can alleviate multiple disadvantages relevant in homicide victimization at an early age. PMID:24811288

  17. Gene delivery of Homer1c rescues spatial learning in a rodent model of cognitive aging.

    PubMed

    Gerstein, Hilary; Lindstrom, Mary J; Burger, Corinna

    2013-08-01

    Homer1c has been shown to play a role in learning and memory. Overexpression of Homer1c in the hippocampus can improve memory in normal rats and can also rescue spatial learning deficits in Homer1 knockout mice. In a previous study, we found that Homer1c mRNA is upregulated after a spatial learning paradigm in aged rats that successfully learn the task, when compared to aged rats that are learning-impaired (AI). This study was designed to validate the role of Homer1c in successful cognitive aging. In this article, we report that gene delivery of Homer1c into the hippocampus of aged learning-impaired rats significantly improves individual performance on an object location memory task. The learning ability of these rats on the Morris Water Maze was also superior to that of AI control rats. In summary, using 2 independent spatial memory tasks, we demonstrate that Homer1c is sufficient to improve the spatial learning deficits in a rodent model of cognitive aging. These results point to Homer1c as a potential therapeutic target for improving age-related cognitive impairment. PMID:23523268

  18. Modelling of the aging behavior of polyamide 12 powder during laser melting process

    NASA Astrophysics Data System (ADS)

    Drummer, Dietmar; Wudy, Katrin; Drexler, Maximilian

    2015-05-01

    Concerning individualization, the requirements to products have increased. Additive manufacturing technologies, such as selective laser melting allow manufacturing of complex parts without tools and forms. Due to this additive manufacturing processes comply, in opposite to conventional techniques, with these increased demands on processing technology. Due to the high temperature during processing, a degradation of the used plastic powder occurs. The non-molten material in the building chamber, the so-called partcake, can be removed after building from the finished component and reused for another process. To realize reproducible part properties refreshing of partcake powder with 30 up to 50 % virgin powder is necessary. However, these refreshing strategies lead to varying component properties due to an undefined aging state. Previous investigations on oven aged powder for selective laser melting showed for short periods of storage near the melting point thermally induced post condensation is the predominate aging effect. Due to post condensation the molecular weight and thus the viscosity increases. This paper focuses on the modeling of the post condensation process to define the aging state of polyamide 12 powder in laser melting process. Therefore the rheological behavior of PA 12 powder in dependency of time and temperature is investigated. Isothermal viscosity measurements are conducted in order to describe the post condensation reaction with a model. With knowledge of the kinetics of the post condensation reaction the state of aging can be predicted in a second step. Thus expected useful life of the powder can be calculated in dependency of the building chamber temperature. These results are then compared with viscosity values of defined aged PA 12 powder to validate the determined model.

  19. Testing seismic hazard models with Be-10 exposure ages for precariously balanced rocks

    NASA Astrophysics Data System (ADS)

    Rood, D. H.; Anooshehpoor, R.; Balco, G.; Brune, J.; Brune, R.; Ludwig, L. Grant; Kendrick, K.; Purvance, M.; Saleeby, I.

    2012-04-01

    Currently, the only empirical tool available to test maximum earthquake ground motions spanning timescales of 10 ky-1 My is the use of fragile geologic features, including precariously balanced rocks (PBRs). The ages of PBRs together with their areal distribution and mechanical stability ("fragility") constrain probabilistic seismic hazard analysis (PSHA) over long timescales; pertinent applications include the USGS National Seismic Hazard Maps (NSHM) and tests for ground motion models (e.g., Cybershake). Until recently, age constraints for PBRs were limited to varnish microlamination (VML) dating techniques and sparse cosmogenic nuclide data; however, VML methods yield minimum limiting ages for individual rock surfaces, and the interpretations of cosmogenic nuclide data were ambiguous because they did not account for the exhumation history of the PBRs or the complex shielding of cosmic rays. We have recently published a robust method for the exposure dating of PBRs combining Be-10 profiles, a numerical model, and a three-dimensional model for each PBR constructed using photogrammetry (Balco et al., 2011, Quaternary Geochronology). Here, we use this method to calculate new exposure ages and fragilities for 6 PBRs in southern California (USA) near the San Andreas, San Jacinto, and Elsinore faults at the Lovejoy Buttes, Round Top, Pacifico, Beaumont South, Perris, and Benton Road sites (in addition to the recently published age of 18.7 +/- 2.8 ka for a PBR at the Grass Valley site). We combine our ages and fragilities for each PBR, and use these data to test the USGS 2008 NSHM PGA with 2% in 50 year probability, USGS 2008 PSHA deaggregations, and basic hazard curves from USGS 2002 NSHM data.

  20. Testing seismic hazard models with Be-10 exposure ages for precariously balanced rocks

    NASA Astrophysics Data System (ADS)

    Rood, D. H.; Anooshehpoor, R.; Balco, G.; Biasi, G. P.; Brune, J. N.; Brune, R.; Grant Ludwig, L.; Kendrick, K. J.; Purvance, M.; Saleeby, I.

    2012-12-01

    Currently, the only empirical tool available to test maximum earthquake ground motions spanning timescales of 10 ky-1 My is the use of fragile geologic features, including precariously balanced rocks (PBRs). The ages of PBRs together with their areal distribution and mechanical stability ("fragility") constrain probabilistic seismic hazard analysis (PSHA) over long timescales; pertinent applications include the USGS National Seismic Hazard Maps (NSHM) and tests for ground motion models (e.g., Cybershake). Until recently, age constraints for PBRs were limited to varnish microlamination (VML) dating techniques and sparse cosmogenic nuclide data; however, VML methods yield minimum limiting ages for individual rock surfaces, and the interpretations of cosmogenic nuclide data were ambiguous because they did not account for the exhumation history of the PBRs or the complex shielding of cosmic rays. We have recently published a robust method for the exposure dating of PBRs combining Be-10 profiles, a numerical model, and a three-dimensional shape model for each PBR constructed using photogrammetry (Balco et al., 2011, Quaternary Geochronology). Here, we use our published method to calculate new exposure ages for PBRs at 6 sites in southern California near the San Andreas, San Jacinto, and Elsinore faults, including: Lovejoy Buttes (9 +/- 1 ka), Round Top (35 +/- 1 ka), Pacifico (19 +/- 1 ka, but with a poor fit to data), Beaumont South (17 +/- 2 ka), Perris (24 +/- 2 ka), and Benton Road (40 +/- 1 ka), in addition to the recently published age of 18.5 +/- 2.0 ka for a PBR at the Grass Valley site. We combine our ages and fragilities for each PBR, and use these data to test the USGS 2008 NSHM PGA with 2% in 50 year probability, USGS 2008 PSHA deaggregations, and basic hazard curves from USGS 2002 NSHM data. Precariously balanced rock in southern California

  1. Comprehensive stellar population models and the disentanglement of age and metallicity effects

    NASA Technical Reports Server (NTRS)

    Worthey, Guy

    1994-01-01

    The construction of detailed models for intermediate and old stellar populations is described. Input parameters include metallicity (-2 less than (Fe/H) less than 0.5), single-burst age (between 1.5 and 17 Gyr), and initial mass function (IMF) exponent. Quantities output include broadband magnitudes, spectral energy distributions, surface brightness fluctuation magnitudes, and a suite of 21 absorption feature indices. The models are checked against a wide variety of available observations. Examinations of model output yield the following conclusions. (1) If the percentage change delta age/delta Z approximately equals 3/2 for two populations, they will appear almost identical in most indices. A few indices break this degeneracy by being either more abundance sensitive (Fe4668, Fe5015, Fe5709, and Fe5782) or more age sensitive (G4300, H beta, and presumably higher order Balmer lines) than usual. (2) Present uncertainties in stellar evolution are of the same magnitude as the effects of IMF and Y in the indices studied. (3) Changes in abundance ratios (like (Mg/Fe)) are predicted to be readily apparent in the spectra of old stellar populations. (4) The I-band flux of a stellar population is predicted to be nearly independent of metallicity and only modestly sensitive to age. The I band is therefore recommended for standard candle work or studies of M/L in galaxies. Other conclusions stem from this work. (1) Intercomparison of models and observations of two TiO indices seem to indicate variation of the (V/Ti) ratio among galaxies, but it is not clear how this observation ties into the standard picture of chemical enrichment. (2) Current estimates of (Fe/H) for the most metal-rich globulars that are based on integrated indices are probably slightly too high. (3) Colors of population models from different authors exhibit a substantial range. At solar metallicity and 13 Gyr, this range corresponds to an age error of roughly +/- 7 Gyr. Model colors from different authors

  2. Impairments of Synaptic Plasticity in Aged Animals and in Animal Models of Alzheimer's Disease

    PubMed Central

    Balietti, Marta; Tamagnini, Francesco; Fattoretti, Patrizia; Burattini, Costanza; Casoli, Tiziana; Platano, Daniela; Lattanzio, Fabrizia

    2012-01-01

    Abstract Aging is associated with a gradual decline in cognitive functions, and more dramatic cognitive impairments occur in patients affected by Alzheimer's disease (AD). Electrophysiological and molecular studies performed in aged animals and in animal models of AD have shown that cognitive decline is associated with significant modifications in synaptic plasticity (i.e., activity-dependent changes in synaptic strength) and have elucidated some of the cellular mechanisms underlying this process. Morphological studies have revealed a correlation between the quality of memory performance and the extent of structural changes of synaptic contacts occurring during memory consolidation. We briefly review recent experimental evidence here. PMID:22533439

  3. Basis for the ICRP`s age-specific biokinetic model for uranium

    SciTech Connect

    Leggett, R.W.

    1994-12-01

    In an effort motivated largely by the Chernobyl nuclear accident, the International Commission on Radiological Protection (ICRP) is developing age-specific biokinetic models and dose coefficients for environmentally important radionuclides. This paper describes the ICRP`s age-specific biokinetic model for uranium. The model is constructed within a physiologically based framework originally developed for application to the alkaline earth elements but sufficiently general to apply to the larger class of bone-volume-seeking elements. Transfer rates for a reference adult are based mainly on: (1) measurements of uranium in blood and excreta of several human subjects who were intravenously injected with uranium; (2) postmortem measurements of uranium in tissues of some of those subjects; (3) postmortem measurements of uranium in tissues of occupationally and non-occupationally exposed subjects; (4) data on baboons, dogs, and smaller laboratory animals exposed to uranium for experimental purposes; and (5) consideration of the physiological processes thought to control retention and translocation of uranium in the body. Transfer rates for the adult are extended to children by application of a set of generic assumptions applied by the ICRP to calcium-like elements. These assumptions were derived mainly from observations of the age-specific biokinetics of the alkaline earth elements and lead in humans and laboratory animals but are consistent with available age-specific biokinetic data on uranium. 82 refs., 17 figs., 8 tabs.

  4. Analyzing aging under oscillatory strain field through the soft glassy rheology model.

    PubMed

    Kaushal, Manish; Joshi, Yogesh M

    2016-06-28

    In this work, we solve the Soft Glassy Rheology (SGR) model under application of oscillatory deformation field with varying magnitudes of strain as well as frequency for different noise temperatures. In the glassy domain, the SGR model undergoes time evolution of elastic modulus. Increase in strain magnitude beyond the linear regime is observed to enhance the rate of aging as manifested by a faster evolution of elastic modulus with increase in strain amplitude due to overaging. However at higher strain magnitudes, the rejuvenation effect starts dominating over the aging, thereby reducing the rate at which elastic modulus evolves. We also plot the aging phase diagram describing an occurrence of the linear, the overaging, and the rejuvenation regimes as a function of strain and frequency for different noise temperatures. The aging phase diagram suggests that while the linear regime remains unaffected by the changes in frequency and noise temperature, the width of the overaging regime increases with increase in frequency and noise temperature. We also study the time evolution of the shapes of relaxation time spectra as a function of strain amplitude, which renders further insight into the overaging and the rejuvenation behavior. While the phenomenon of overaging is observed to be an inherent character of the SGR model, experimentally not all the materials demonstrate overaging. Such a discrepancy suggests that the energy well depths before and after a yielding event may not be completely uncorrelated as assumed in the SGR formalism. PMID:27369524

  5. Early-life stress and reproductive cost: A two-hit developmental model of accelerated aging?

    PubMed

    Shalev, Idan; Belsky, Jay

    2016-05-01

    Two seemingly independent bodies of research suggest a two-hit model of accelerated aging, one highlighting early-life stress and the other reproduction. The first, informed by developmental models of early-life stress, highlights reduced longevity effects of early adversity on telomere erosion, whereas the second, informed by evolutionary theories of aging, highlights such effects with regard to reproductive cost (in females). The fact that both early-life adversity and reproductive effort are associated with shorter telomeres and increased oxidative stress raises the prospect, consistent with life-history theory, that these two theoretical frameworks currently informing much research are tapping into the same evolutionary-developmental process of increased senescence and reduced longevity. Here we propose a mechanistic view of a two-hit model of accelerated aging in human females through (a) early-life adversity and (b) early reproduction, via a process of telomere erosion, while highlighting mediating biological embedding mechanisms that might link these two developmental aging processes. PMID:27063083

  6. Epigenetic contribution to age distribution of mortality within the Penna model.

    PubMed

    Magdoń-Maksymowicz, M S; Maksymowicz, A Z

    2015-06-01

    Some modifications of the simple asexual Penna model, enriched by epigenetic contributions, are presented. The standard bit-string Penna model of biological aging and population evolution is based on an inherited DNA structure which defines the future life of a newly born individuals, when genes are activated by the biological clock, and the predefined genetic death is fully controlled by the number of defected genes. Epigenomes allow to introduce additional mechanism of gene activation or silencing without affecting the DNA genome itself. It may be either inherited or may reflect external, environmental factors. In the presented model, information read from the introduced epigenome may alter gene expression that may be stopped or re-activated. We concentrate on the influence of epigenetics on the age a distribution of genetic mortality m(a). Changes in m(a) are strong for the case of inherited epigenetic contribution with nearly perfect inheritance and 'positive' epigenome that partly ignores the 'bad' mutations. We conclude that the epigenetic contribution may influence population structure m(a) and could be, at least partly, responsible for deviation of m(a) distribution from the Gompertz law. In short, we claim that proposed epigenetic contribution may be seen as a candidate for possible explanation of observed deviation from the Gompertz law, also among senior members of society. A very simple model was used in this paper and many crucial mechanisms of biological aging were omitted. Therefore, further work based on a more realistic models is necessary. PMID:25666268

  7. Optimal control for an age-structured model for the transmission of hepatitis B.

    PubMed

    Djidjou Demasse, Ramses; Tewa, Jean-Jules; Bowong, Samuel; Emvudu, Yves

    2016-08-01

    One of the characteristics of HBV transmission is the age structure of the host population and the vertical transmission of the disease. That is the infection is transmitted directly from infected mother to an embryo, fetus, or baby during pregnancy or childbirth (the perinatal infection). We formulated an age-structured model for the transmission dynamics of HBV with differential infectivity: symptomatic and asymptomatic infections. The model without intervention strategies is completely analyzed. We compute the basic reproduction number which determines the outcome of the disease. We also compute equilibria and study their stability. The sensitivity analysis of the initial model parameters is performed (to determine the impact of control-related parameters on outbreak severity). Using optimal control theory, we determine the cost-effective balance of three interventions methods which minimizes HBV-related deaths as well as the costs associated with intervention. PMID:26676356

  8. A Hero for the Aged? The Townsend Movement, the Political Mediation Model, and U.S. Old-Age Policy, 1934-1950.

    ERIC Educational Resources Information Center

    Amenta, Edwin; And Others

    1992-01-01

    Examines the Depression era Townsend Movement that pressed for old age pensions. Compares this movement with a model social movement to explore what facilitates the development of movements and what determines their success or failure. Concludes that the political mediation model explains successes as reinforced political action with strong member…

  9. Clarifying hierarchical age-period-cohort models: A rejoinder to Bell and Jones.

    PubMed

    Reither, Eric N; Land, Kenneth C; Jeon, Sun Y; Powers, Daniel A; Masters, Ryan K; Zheng, Hui; Hardy, Melissa A; Keyes, Katherine M; Fu, Qiang; Hanson, Heidi A; Smith, Ken R; Utz, Rebecca L; Yang, Y Claire

    2015-11-01

    Previously, Reither et al. (2015) demonstrated that hierarchical age-period-cohort (HAPC) models perform well when basic assumptions are satisfied. To contest this finding, Bell and Jones (2015) invent a data generating process (DGP) that borrows age, period and cohort effects from different equations in Reither et al. (2015). When HAPC models applied to data simulated from this DGP fail to recover the patterning of APC effects, B&J reiterate their view that these models provide "misleading evidence dressed up as science." Despite such strong words, B&J show no curiosity about their own simulated data--and therefore once again misapply HAPC models to data that violate important assumptions. In this response, we illustrate how a careful analyst could have used simple descriptive plots and model selection statistics to verify that (a) period effects are not present in these data, and (b) age and cohort effects are conflated. By accounting for the characteristics of B&J's artificial data structure, we successfully recover the "true" DGP through an appropriately specified model. We conclude that B&Js main contribution to science is to remind analysts that APC models will fail in the presence of exact algebraic effects (i.e., effects with no random/stochastic components), and when collinear temporal dimensions are included without taking special care in the modeling process. The expanded list of coauthors on this commentary represents an emerging consensus among APC scholars that B&J's essential strategy--testing HAPC models with data simulated from contrived DGPs that violate important assumptions--is not a productive way to advance the discussion about innovative APC methods in epidemiology and the social sciences. PMID:26277370

  10. Ice-age simulations with a caving ice-sheet model

    SciTech Connect

    Pollard, D.

    1982-01-01

    Further extensions and results of a simple northern hemispheric ice-sheet model are described for the Quaternary ice ages. The basic model predicts ice thickness and bedrock deformation in a north-south cross section, with a prescribed snow-budget distribution shifted uniformly in space to represent the orbital perturbations. An ice calving parameterization crudely representing proglacial lakes or marine incursions can attack the ice whenever the tip drops below sea level. As in Pollard (1982a) the basic model produces a large approx. 100,000-yr response and agrees fairly well with the delta/sup 18/O deep-sea core records. Three extensions of the model are described: an alternative treatment of bedrock deformation, a more realistic ice-shelf model of ice calving, and a generalized parameterization for such features as the North Atlantic deglacial meltwater layer. Much the same ice-age simulations and agreement with the delta/sup 18/O records as with the original model are still obtained. The observed phase-correlation between the 100,000-yr cycles and eccentricity is examined. First, the model is shown to give a approx. 100,000-yr response to nearly any kind of higher-frequency forcing. Although over the last two million years the model phase is mainly controlled by the precessional modulation due to eccentricity, over just the last 600,000-yr the observed phase can also be simulated with eccentricity held constant. A definitive conclusion on the phase-control of the Quaternary ice ages is prevented by uncertainty in the deep-sea core time scales before approx. 600,000-yr B.P. In an appendix the model is applied to West Antarctica where unforced internal oscillations occur with periods of about 50,000-yr.

  11. Timing the second birth: fecundability models for selected race and age groups in Hawaii.

    PubMed

    Swanson, D A

    1986-12-01

    This article tests exponential models for fecundability for use in predicting the timing of the second birth in a non-contracepting population, using data from Hawaii for reference. The paper begins with an extensive review of the literature on mathematical models for birth intervals. The most common problem with prior studies is that the reference data are often biased with uncontrolled parameters such as maternal age, abortion history, lactation practice and pregnancy planning. Pertinent bias in the present data is evaluated. The principal tool used here is an exponential distribution, maximum-likelihood method, involving partial differential equations. The model was constructed by subjecting it to 3 steps: 1) it was tested for exponentiality with a Gail-Gastwirth test that does not depend upon an unknown parameter; 2) the reciprocal of the mean second birth interval was calculated for each group that passed the first test; 3) the estimated frequencies were tested against observed by the chi-squared goodness of fit test. The results are tabulated as separate racial groups, combined races, and age groups. Fecundabilities varied widely by age within all races. For all races, rates were .07045, .03423 and .02777 for ages 20-24, 25-29, and 30-34. Thus the results suggest that fecundability rates are largely determined by age related factors associated with coital frequency, rather than by racial or physiological variations. Other factors potentially influencing fecundability in actual data or models are discussed, such as period effects, the "intendedness" of pregnancy, types of non-live birth intervals, lactation, induced and spontaneous abortion, and differences in pre- and post-demographic transition populations. Finally appendices are added discussing cohort size bias, presenting data set documentation and evaluating the length of pregnancy term and post-partum sterility in the data used here. PMID:12268733

  12. Cycle ageing analysis of a LiFePO4/graphite cell with dynamic model validations: Towards realistic lifetime predictions

    NASA Astrophysics Data System (ADS)

    Sarasketa-Zabala, E.; Gandiaga, I.; Martinez-Laserna, E.; Rodriguez-Martinez, L. M.; Villarreal, I.

    2015-02-01

    The present investigation work compares cycling ageing behaviour upon constant operation conditions (static tests) with degradation under non-constant schemes (dynamic tests), through a novel methodology for ageing model dynamic validation. A LFP-based Li-ion cell performance loss is analysed using a DOD and C-rate stress factors Ah-throughput-domain characterisation method, and represented using a semi-empirical model. The proposed stepwise validation approach enables assessing the static ageing tests acceleration factor and systematically improving the ageing model. The result is a simple but comprehensive model. The predictions root-mean-square error, under dynamic cycling operation conditions, is just 1.75%.

  13. Positive mutations and mutation-dependent Verhulst factor in Penna ageing model

    NASA Astrophysics Data System (ADS)

    Moss de Oliveira, S.; Stauffer, D.; de Oliveira, P. M. C.; Sá Martins, J. S.

    2004-02-01

    We modify twice the Penna model for biological ageing. First, we introduce back (good) mutations and a memory for them into the model. It allows us to observe an improvement of the species fitness over long-time scales as well as punctuated equilibrium. Second, we adopt a food/space competition factor that depends on the number of accumulated mutations in the individuals genomes, and get rid of the fixed limiting number of allowed mutations. Besides reproducing the main results of the standard model, we also observe a mortality maximum for the oldest old.

  14. A Diffusion Model Analysis of Adult Age Differences in Episodic and Semantic Long-Term Memory Retrieval

    ERIC Educational Resources Information Center

    Spaniol, Julia; Madden, David J.; Voss, Andreas

    2006-01-01

    Two experiments investigated adult age differences in episodic and semantic long-term memory tasks, as a test of the hypothesis of specific age-related decline in context memory. Older adults were slower and exhibited lower episodic accuracy than younger adults. Fits of the diffusion model (R. Ratcliff, 1978) revealed age-related increases in…

  15. The effects of mixing on stratospheric Age of Air in global models

    NASA Astrophysics Data System (ADS)

    Garny, Hella; Birner, Thomas; Bönisch, Harald

    2014-05-01

    The stratospheric Brewer-Dobson circulation is often quantified by the integrated transport measure stratospheric age of air (AoA). AoA is influenced both by mean transport along the residual circulation and by two-way mixing. Therefore, AoA is a good measure of the overall capabilities of a global model to simulate stratospheric transport. Currently, a large spread in the simulation of AoA by global models is found. In this study we use a method that allows us to quantify the effect of mixing on AoA from global model data. AoA is contrasted with a hypothetical age - the age air would have if it was only transported by the residual circulation, the residual circulation transit time (RCTT). The difference of AoA and RCTT is interpreted as the additional aging by mixing. Mixing causes air to be older almost in the entire lower stratosphere (AoA > RCTT). This increase in AoA by mixing is largely due to mixing between the tropics and extratropics, that leads to recirculation of air through the stratosphere. A "mixing efficiency" is defined as the ratio of the two-way mixing mass flux across the subtropical barrier to the net (residual) mass flux. This mixing efficiency controls the ratio of tropical mean AoA to RCTT, and thus the relative increase in AoA by mixing. These diagnostics are applied to a set of global model simulations to examine the causes for the spread in the simulation of AoA in different models. It is found that both differences in the residual circulation strength and in mixing contribute to the spread in simulated AoA. The mixing efficiency varies strongly between models - leading to differences in AoA between models even if the residual circulation strength did not differ. Possible causes for the differences in the mixing efficiency might be found in the model dynamics (e.g. the wave spectrum) and/or numerics (e.g. the advection scheme used). The different mixing efficiencies in models also modulate the response of AoA to long-term changes in the

  16. The influence of aging on poststroke depression using a rat model via middle cerebral artery occlusion.

    PubMed

    Boyko, Matthew; Kutz, Ruslan; Gruenbaum, Benjamin F; Cohen, Hagit; Kozlovsky, Nitsan; Gruenbaum, Shaun E; Shapira, Yoram; Zlotnik, Alexander

    2013-12-01

    Poststroke depression (PSD) is the most frequent psychological sequela following stroke. While previous studies describe the impact of age on brain infarct volume, brain edema, and blood-brain barrier (BBB) breakdown following ischemia, the role of age on PSD has yet to be described. Here, we examine the influence of age on PSD progression in a rat model of PSD by middle cerebral artery occlusion (MCAO). One hundred forty-three rats were divided into three groups. 48 rats 20 weeks of age underwent a sham procedure, 51 rats 20 weeks of age had MCAO, and 44 rats 22-26 months of age had MCAO. Groups were further divided into two subgroups. The first subgroup was used to measure infarct lesion volume, brain edema, and BBB breakdown at 24 h. In the second subgroup at 3 weeks after MCAO, rats were subjected to a sucrose preference test, two-way shuttle avoidance task, forced swimming test, and a brain-derived neurotrophic factor (BDNF) protein level measurement. Total and striatal infarct volume, brain edema, and BBB breakdown in the striatum were increased in older rats, as compared with younger rats. While both old and young rats exhibited depressive-like behaviors on each of the behavioral tests and lower BDNF levels post-MCAO, as compared with control rats, there were no differences between old and young rats. Although older rats suffered from larger infarct volumes, increased brain edema and more BBB disruption following MCAO, the lack of behavioral differences between young and old rats suggests that there was no effect of rat age on the incidence of PSD. PMID:23761136

  17. Estimating Risks of Heat Strain by Age and Sex: A Population-Level Simulation Model

    PubMed Central

    Glass, Kathryn; Tait, Peter W.; Hanna, Elizabeth G.; Dear, Keith

    2015-01-01

    Individuals living in hot climates face health risks from hyperthermia due to excessive heat. Heat strain is influenced by weather exposure and by individual characteristics such as age, sex, body size, and occupation. To explore the population-level drivers of heat strain, we developed a simulation model that scales up individual risks of heat storage (estimated using Myrup and Morgan’s man model “MANMO”) to a large population. Using Australian weather data, we identify high-risk weather conditions together with individual characteristics that increase the risk of heat stress under these conditions. The model identifies elevated risks in children and the elderly, with females aged 75 and older those most likely to experience heat strain. Risk of heat strain in males does not increase as rapidly with age, but is greatest on hot days with high solar radiation. Although cloudy days are less dangerous for the wider population, older women still have an elevated risk of heat strain on hot cloudy days or when indoors during high temperatures. Simulation models provide a valuable method for exploring population level risks of heat strain, and a tool for evaluating public health and other government policy interventions. PMID:25993102

  18. Rule-Based Cell Systems Model of Aging using Feedback Loop Motifs Mediated by Stress Responses

    PubMed Central

    Kriete, Andres; Bosl, William J.; Booker, Glenn

    2010-01-01

    Investigating the complex systems dynamics of the aging process requires integration of a broad range of cellular processes describing damage and functional decline co-existing with adaptive and protective regulatory mechanisms. We evolve an integrated generic cell network to represent the connectivity of key cellular mechanisms structured into positive and negative feedback loop motifs centrally important for aging. The conceptual network is casted into a fuzzy-logic, hybrid-intelligent framework based on interaction rules assembled from a priori knowledge. Based upon a classical homeostatic representation of cellular energy metabolism, we first demonstrate how positive-feedback loops accelerate damage and decline consistent with a vicious cycle. This model is iteratively extended towards an adaptive response model by incorporating protective negative-feedback loop circuits. Time-lapse simulations of the adaptive response model uncover how transcriptional and translational changes, mediated by stress sensors NF-κB and mTOR, counteract accumulating damage and dysfunction by modulating mitochondrial respiration, metabolic fluxes, biosynthesis, and autophagy, crucial for cellular survival. The model allows consideration of lifespan optimization scenarios with respect to fitness criteria using a sensitivity analysis. Our work establishes a novel extendable and scalable computational approach capable to connect tractable molecular mechanisms with cellular network dynamics underlying the emerging aging phenotype. PMID:20585546

  19. Touchscreen-Based Cognitive Tasks Reveal Age-Related Impairment in a Primate Aging Model, the Grey Mouse Lemur (Microcebus murinus)

    PubMed Central

    2014-01-01

    Mouse lemurs are suggested to represent promising novel non-human primate models for aging research. However, standardized and cross-taxa cognitive testing methods are still lacking. Touchscreen-based testing procedures have proven high stimulus control and reliability in humans and rodents. The aim of this study was to adapt these procedures to mouse lemurs, thereby exploring the effect of age. We measured appetitive learning and cognitive flexibility of two age groups by applying pairwise visual discrimination (PD) and reversal learning (PDR) tasks. On average, mouse lemurs needed 24 days of training before starting with the PD task. Individual performances in PD and PDR tasks correlate significantly, suggesting that individual learning performance is unrelated to the respective task. Compared to the young, aged mouse lemurs showed impairments in both PD and PDR tasks. They needed significantly more trials to reach the task criteria. A much higher inter-individual variation in old than in young adults was revealed. Furthermore, in the PDR task, we found a significantly higher perseverance in aged compared to young adults, indicating an age-related deficit in cognitive flexibility. This study presents the first touchscreen-based data on the cognitive skills and age-related dysfunction in mouse lemurs and provides a unique basis to study mechanisms of inter-individual variation. It furthermore opens exciting perspectives for comparative approaches in aging, personality, and evolutionary research. PMID:25299046

  20. Type 2 diabetes model TSOD mouse is exposed to oxidative stress at young age

    PubMed Central

    Murotomi, Kazutoshi; Umeno, Aya; Yasunaga, Mayu; Shichiri, Mototada; Ishida, Noriko; Abe, Hiroko; Yoshida, Yasukazu; Nakajima, Yoshihiro

    2014-01-01

    Tsumura Suzuki Obese Diabetes (TSOD) mouse, a model of obese type 2 diabetes, older than around 11 weeks of age develops diabetic phenotypes. Previous studies have indicated that the development of diabetes is partly due to three loci associated with body weight and glucose homeostasis. However, little is known about the initial events triggering the development of the diabetic phenotypes in TSOD mouse. Here, we investigated the alteration of diabetes-related parameters, including the levels of blood glucose and inflammatory cytokines, and the oxidative stress status, in young TSOD mice. TSOD mice at 5 weeks of age showed increases in body weight and plasma total cholesterol level, but not hyperglycemia or impaired glucose tolerance, compared with age-matched control Tsumura Suzuki Non-Obese (TSNO) mice. Plasma tumor necrosis factor (TNF)-α and interleukin (IL)-6 were not detected in TSOD mice at 5 weeks of age. However, plasma total hydroxyoctadecadienoic acid (tHODE), a biomarker of oxidative stress, was increased in TSOD mice relative to TSNO mice at same age. The results demonstrated that young TSOD mice are exposed to oxidative stress before developing the diabetic phenotypes, and suggested that oxidative stress is an initial event triggering the development of diabetes in TSOD mice. PMID:25411529

  1. Cryptococcus neoformans constitutes an ideal model organism to unravel the contribution of cellular aging to the virulence of chronic infections.

    PubMed

    Bouklas, Tejas; Fries, Bettina C

    2013-08-01

    Aging affects all organisms, from unicellular yeasts to multicellular humans. Studies in model organisms demonstrate that the pathways that mediate the two forms of aging, replicative and chronological, are highly conserved. Most studies are focused on the effect of aging on an individual cell rather than a whole population. Complex longevity regulation, however, makes aging a highly adaptive trait that is subject to natural selection. Recent studies have shed light on the potential relevance of aging in fungal pathogens, which undergo replicative aging when they expand in the host environment. Hence, pathogens causing chronic infections can constitute ideal model organisms in unraveling the contribution of selection to aging within a population and help elucidate the contribution of aging itself to the virulence of infections. PMID:23631868

  2. Modelling galactic conformity with the colour-halo age relation in the Illustris simulation

    NASA Astrophysics Data System (ADS)

    Bray, Aaron D.; Pillepich, Annalisa; Sales, Laura V.; Zhu, Emily; Genel, Shy; Rodriguez-Gomez, Vicente; Torrey, Paul; Nelson, Dylan; Vogelsberger, Mark; Springel, Volker; Eisenstein, Daniel J.; Hernquist, Lars

    2016-01-01

    Comparisons between observational surveys and galaxy formation models find that dark matter haloes' mass can largely explain their galaxies' stellar mass. However, it remains uncertain whether additional environmental variables, known as assembly bias, are necessary to explain other galaxy properties. We use the Illustris simulation to investigate the role of assembly bias in producing galactic conformity by considering 18 000 galaxies with Mstellar > 2 × 109 M⊙. We find a significant signal of galactic conformity: out to distances of about 10 Mpc, the mean red fraction of galaxies around redder galaxies is higher than around bluer galaxies at fixed stellar mass. Dark matter haloes exhibit an analogous conformity signal, in which the fraction of haloes formed at earlier times (old haloes) is higher around old haloes than around younger ones at fixed halo mass. A plausible interpretation of galactic conformity is the combination of the halo conformity signal with the galaxy colour-halo age relation: at fixed stellar mass, particularly towards the low-mass end, Illustris' galaxy colours correlate with halo age, with the reddest galaxies (often satellites) preferentially found in the oldest haloes. We explain the galactic conformity effect with a simple semi-empirical model, assigning stellar mass via halo mass (abundance matching) and galaxy colour via halo age (age matching). Regarding comparison to observations, we conclude that the adopted selection/isolation criteria, projection effects, and stacking techniques can have a significant impact on the measured amplitude of the conformity signal.

  3. Factors influencing the cognitive and neural effects of hormone treatment during aging in a rodent model

    PubMed Central

    Chisholm, Nioka C.; Juraska, Janice M.

    2013-01-01

    Whether hormone treatment alters brain structure or has beneficial effects on cognition during aging has recently become a topic of debate. Although previous research has indicated that hormone treatment benefits memory in menopausal women, several newer studies have shown no effect or detrimental effects. These inconsistencies emphasize the need to evaluate the role of hormones in protecting against age-related cognitive decline in an animal model. Importantly, many studies investigating the effects of estrogen and progesterone on cognition and related brain regions have used young adult animals, which respond differently than aged animals. However, when only the studies that have examined the effects of hormone treatment in an aging model are reviewed, there are still varied behavioral and neural outcomes. This article reviews some of the important factors that can influence the behavioral and neural outcomes of hormone treatment including the type of estrogen administered, whether or not estrogen is combined with progesterone and if so, the type of progesterone used, as well as the route, mode, and length of treatment. How these factors influence cognitive outcomes highlights the importance of study design and avoiding generalizations from a small number of studies. PMID:23419893

  4. Effects of age, dietary, and behavioral enrichment on brain mitochondria in a canine model of human aging.

    PubMed

    Head, E; Nukala, V N; Fenoglio, K A; Muggenburg, B A; Cotman, C W; Sullivan, P G

    2009-11-01

    Dogs develop cognitive decline and a progressive accumulation of oxidative damage. In a previous longitudinal study, we demonstrated that aged dogs treated with either an antioxidant diet or with behavioral enrichment show cognitive improvement. The antioxidant diet included cellular antioxidants (vitamins E and C, fruits and vegetables) and mitochondrial cofactors (lipoic acid and carnitine). Behavioral enrichment consisted of physical exercise, social enrichment, and cognitive training. We hypothesized that the antioxidant treatment improved neuronal function through increased mitochondrial function. Thus, we measured reactive oxygen species (ROS) production and bioenergetics in mitochondria isolated from young, aged, and treated aged animals. Aged canine brain mitochondria show significant increases in ROS production and a reduction in NADH-linked respiration. Mitochondrial function (ROS and NADH-linked respiration) was improved selectively in aged dogs treated with an antioxidant diet. In contrast, behavioral enrichment had no effect on any mitochondrial parameters. These results suggest that an antioxidant diet improves cognition by maintaining mitochondrial homeostasis, which may be an independent molecular pathway not engaged by behavioral enrichment. PMID:19703441

  5. Cscibox: A Software System for Age-Model Construction and Evaluation

    NASA Astrophysics Data System (ADS)

    Bradley, E.; Anderson, K. A.; Marchitto, T. M., Jr.; de Vesine, L. R.; White, J. W. C.; Anderson, D. M.

    2014-12-01

    CSciBox is an integrated software system for the construction and evaluation of age models of paleo-environmetal archives, both directly dated and cross dated. The time has come to encourage cross-pollinization between earth science and computer science in dating paleorecords. This project addresses that need. The CSciBox code, which is being developed by a team of computer scientists and geoscientists, is open source and freely available on github. The system employs modern database technology to store paleoclimate proxy data and analysis results in an easily accessible and searchable form. This makes it possible to do analysis on the whole core at once, in an interactive fashion, or to tailor the analysis to a subset of the core without loading the entire data file. CSciBox provides a number of 'components' that perform the common steps in age-model construction and evaluation: calibrations, reservoir-age correction, interpolations, statistics, and so on. The user employs these components via a graphical user interface (GUI) to go from raw data to finished age model in a single tool: e.g., an IntCal09 calibration of 14C data from a marine sediment core, followed by a piecewise-linear interpolation. CSciBox's GUI supports plotting of any measurement in the core against any other measurement, or against any of the variables in the calculation of the age model-with or without explicit error representations. Using the GUI, CSciBox's user can import a new calibration curve or other background data set and define a new module that employs that information. Users can also incorporate other software (e.g., Calib, BACON) as 'plug ins.' In the case of truly large data or significant computational effort, CSciBox is parallelizable across modern multicore processors, or clusters, or even the cloud. The next generation of the CSciBox code, currently in the testing stages, includes an automated reasoning engine that supports a more-thorough exploration of plausible age models

  6. Spectroscopic age and metallicity for a sample of Globular Clusters from Stellar Population Models

    NASA Astrophysics Data System (ADS)

    Stock, M. J.; Calderón, P.

    2009-05-01

    We present spectroscopic age and metallicity predictions for a sample of 20 Globular Clusters in the massive E0 galaxy NGC 1407 (data from Cenarro et al. 2007, AJ, 134, 391) and for the Galacic Globular Clusters data from the Library of Integrated Spectra of Galactic Globular Clusters (GGC's) from Schiavon et al. (2005, ApJS, 160, 163) including the widely studied 47 Tuc cluster. Using index-index plots we compared model Single Stellar Populations (SSP's) spectra to the integrated spectra of both samples of Globular Clusters using high resolution line strength indices (Stock, in prep.) and the syntethic SSP's models from P. Coelho (2007, private comm.) as well as the CB07 solar models. For the GC's in NGC1407, the predictions from the syntethic models's with [α /Fe]=0.4 are in good agreement with the results from Cenarro et al. (2007, AJ, 134, 391), taking into account that the dispersion is partially due to the fact that the mean [α/Fe] ratio of the sample is ≈ 0.3 dex, resulting in younger ages and lower metallicities (Thomas et al. 2003, A&A, 401, 429). We observe a bimodal distribution of the Fe4383+ index which is in turn an indicator of metallicity, also seen in Cenarro et al. (2005). The CB07 models predict ages that are widely spread over the plot yielding ages greater than 14 Gyrs. The metallicity derived from these models are very low for almost all the objects (Z < 0.008). The distribution of the GGC's on the syntethic model grid shows a trend in the sense that metal poor clusters are younger than metal rich ones, but this effect might not be real (de Angeli et al. 2005, AJ, 130, 116). For 47 Tuc we estimate an age of ≈ 10 Gyr, and metallicity Z < 0.011 (<[Fe/H]= -0.5) which are both comparable with the values reported in the literature (Carretta et al. 2000; Liu & Chaboyer 2000, ApJ, 544, 818; Schiavon et al. 2002, ApJ, 580, 873; Gratton et al. 2003, A&A, 408, 529).

  7. The ICRP age-specific biokinetic model for lead: validations, empirical comparisons, and explorations.

    PubMed Central

    Pounds, J G; Leggett, R W

    1998-01-01

    The objective of this manuscript is to provide a description of the International Commission for Radiation Protection (ICRP) model and a comparison to other models (the integrated exposure uptake biokinetic [IEUBK] and O'Flaherty models), including the software used with the models, and a comparison of the model predictions for selected situations. The ICRP biokinetic model for Pb is a multicompartmental model for Pb uptake and disposition in children and in adults. The model describes deposition and retention of absorbed Pb in numerous tissues, removal from tissues to plasma, and movement along various routes of excretion. Long-term skeletal behavior of Pb is described in terms of age-specific rates of restructuring of compact and trabecular bone. The ICRP model is more flexible and has wider applicability than the IEUBK model. The major disadvantages are that application of the computer model requires some basic computer skills, and the user must convert the Pb concentrations in food, air, soil, dust, paint, or other media to the amount of Pb ingested or inhaled per day. Direct comparisons between the ICRP model and the IEUBK model are provided by modeling blood Pb levels using the IEUBK v0.99d default Pb uptakes and intake values. The model is used to simulate occupational exposure cases and a controlled Pb inhalation experiment in adult humans. Finally, use of the model to explore situations with limited data is illustrated by simulating the kinetics and disposition of Pb during acute Pb poisoning and chelation therapy in a child. PMID:9860909

  8. Exposure age and ice-sheet model constraints on Pliocene East Antarctic ice sheet dynamics.

    PubMed

    Yamane, Masako; Yokoyama, Yusuke; Abe-Ouchi, Ayako; Obrochta, Stephen; Saito, Fuyuki; Moriwaki, Kiichi; Matsuzaki, Hiroyuki

    2015-01-01

    The Late Pliocene epoch is a potential analogue for future climate in a warming world. Here we reconstruct Plio-Pleistocene East Antarctic Ice Sheet (EAIS) variability using cosmogenic nuclide exposure ages and model simulations to better understand ice sheet behaviour under such warm conditions. New and previously published exposure ages indicate interior-thickening during the Pliocene. An ice sheet model with mid-Pliocene boundary conditions also results in interior thickening and suggests that both the Wilkes Subglacial and Aurora Basins largely melted, offsetting increased ice volume. Considering contributions from West Antarctica and Greenland, this is consistent with the most recent IPCC AR5 estimate, which indicates that the Pliocene sea level likely did not exceed +20 m on Milankovitch timescales. The inception of colder climate since ∼3 Myr has increased the sea ice cover and inhibited active moisture transport to Antarctica, resulting in reduced ice sheet thickness, at least in coastal areas. PMID:25908601

  9. Exposure age and ice-sheet model constraints on Pliocene East Antarctic ice sheet dynamics

    PubMed Central

    Yamane, Masako; Yokoyama, Yusuke; Abe-Ouchi, Ayako; Obrochta, Stephen; Saito, Fuyuki; Moriwaki, Kiichi; Matsuzaki, Hiroyuki

    2015-01-01

    The Late Pliocene epoch is a potential analogue for future climate in a warming world. Here we reconstruct Plio-Pleistocene East Antarctic Ice Sheet (EAIS) variability using cosmogenic nuclide exposure ages and model simulations to better understand ice sheet behaviour under such warm conditions. New and previously published exposure ages indicate interior-thickening during the Pliocene. An ice sheet model with mid-Pliocene boundary conditions also results in interior thickening and suggests that both the Wilkes Subglacial and Aurora Basins largely melted, offsetting increased ice volume. Considering contributions from West Antarctica and Greenland, this is consistent with the most recent IPCC AR5 estimate, which indicates that the Pliocene sea level likely did not exceed +20 m on Milankovitch timescales. The inception of colder climate since ∼3 Myr has increased the sea ice cover and inhibited active moisture transport to Antarctica, resulting in reduced ice sheet thickness, at least in coastal areas. PMID:25908601

  10. Exposure age and ice-sheet model constraints on Pliocene East Antarctic ice sheet dynamics

    NASA Astrophysics Data System (ADS)

    Yamane, Masako; Yokoyama, Yusuke; Abe-Ouchi, Ayako; Obrochta, Stephen; Saito, Fuyuki; Moriwaki, Kiichi; Matsuzaki, Hiroyuki

    2015-04-01

    The Late Pliocene epoch is a potential analogue for future climate in a warming world. Here we reconstruct Plio-Pleistocene East Antarctic Ice Sheet (EAIS) variability using cosmogenic nuclide exposure ages and model simulations to better understand ice sheet behaviour under such warm conditions. New and previously published exposure ages indicate interior-thickening during the Pliocene. An ice sheet model with mid-Pliocene boundary conditions also results in interior thickening and suggests that both the Wilkes Subglacial and Aurora Basins largely melted, offsetting increased ice volume. Considering contributions from West Antarctica and Greenland, this is consistent with the most recent IPCC AR5 estimate, which indicates that the Pliocene sea level likely did not exceed +20 m on Milankovitch timescales. The inception of colder climate since ~3 Myr has increased the sea ice cover and inhibited active moisture transport to Antarctica, resulting in reduced ice sheet thickness, at least in coastal areas.

  11. Comparative modeling of Bronze Age land use in the Malatya Plain (Turkey)

    NASA Astrophysics Data System (ADS)

    Arıkan, Bülent; Restelli, Francesca Balossi; Masi, Alessia

    2016-03-01

    Computational modeling in archeology has proven to be a useful tool in quantifying changes in the paleoenvironment. This especially useful method combines data from diverse disciplines to answer questions focusing on the complex and non-linear aspects of human-environment interactions. The research presented here uses various proxy records to compare the changes in climate during the Bronze Age in the Malatya Plain in eastern Anatolia, which is situated at the northern extremity of northern Mesopotamia. Extensive agropastoral land use modeling was applied to three sites of different size and function in the Malatya Plain during the Early Bronze Age I period to simulate the varying scale and intensity of human impacts in relation to changes in the level of social organization, demography, and temporal length. The results suggest that even in land use types subjected to a light footprint, the scale and intensity of anthropogenic impacts change significantly in relation to the level of social organization.

  12. Parameter sensitivity analysis of a simplified electrochemical and thermal model for Li-ion batteries aging

    NASA Astrophysics Data System (ADS)

    Edouard, C.; Petit, M.; Forgez, C.; Bernard, J.; Revel, R.

    2016-09-01

    In this work, a simplified electrochemical and thermal model that can predict both physicochemical and aging behavior of Li-ion batteries is studied. A sensitivity analysis of all its physical parameters is performed in order to find out their influence on the model output based on simulations under various conditions. The results gave hints on whether a parameter needs particular attention when measured or identified and on the conditions (e.g. temperature, discharge rate) under which it is the most sensitive. A specific simulation profile is designed for parameters involved in aging equations in order to determine their sensitivity. Finally, a step-wise method is followed to limit the influence of parameter values when identifying some of them, according to their relative sensitivity from the study. This sensitivity analysis and the subsequent step-wise identification method show very good results, such as a better fitting of the simulated cell voltage with experimental data.

  13. Age- and bite-structured models for vector-borne diseases.

    PubMed

    Rock, K S; Wood, D A; Keeling, M J

    2015-09-01

    The biology and behaviour of biting insects is a vitally important aspect in the spread of vector-borne diseases. This paper aims to determine, through the use of mathematical models, what effect incorporating vector senescence and realistic feeding patterns has on disease. A novel model is developed to enable the effects of age- and bite-structure to be examined in detail. This original PDE framework extends previous age-structured models into a further dimension to give a new insight into the role of vector biting and its interaction with vector mortality and spread of disease. Through the PDE model, the roles of the vector death and bite rates are examined in a way which is impossible under the traditional ODE formulation. It is demonstrated that incorporating more realistic functions for vector biting and mortality in a model may give rise to different dynamics than those seen under a more simple ODE formulation. The numerical results indicate that the efficacy of control methods that increase vector mortality may not be as great as predicted under a standard host-vector model, whereas other controls including treatment of humans may be more effective than previously thought. PMID:26342239

  14. Accommodating volume-constant age-dependent optical (AVOCADO) model of the crystalline GRIN lens

    PubMed Central

    Sheil, Conor J.; Goncharov, Alexander V.

    2016-01-01

    The purpose of this manuscript is to introduce a new age-dependent model of the human lens with two GRIN power distributions (axial and radial) that allow decoupling of its refractive power and axial optical path length. The aspect ratio of the lens core can be held constant under accommodation, as well as the lens volume by varying the asphericity of the lens external surfaces. The spherical aberration calculated by exact raytracing is shown to be in line with experimental data. The proposed model is compared to previous GRIN models from the literature, and it is concluded that the features of the new model will be useful for GRIN reconstruction in future experimental studies; in particular, studies of the accommodation-dependent properties of the ageing human eye. A proposed logarithmic model of the lens core enables decoupling of three fundamental optical characteristics of the lens, namely axial optical path length, optical power and third-order spherical aberration, without changing the external shape of the lens. Conversely, the near-surface GRIN structure conforms to the external shape of the lens, which is necessary for accommodation modelling. PMID:27231637

  15. Accommodating volume-constant age-dependent optical (AVOCADO) model of the crystalline GRIN lens.

    PubMed

    Sheil, Conor J; Goncharov, Alexander V

    2016-05-01

    The purpose of this manuscript is to introduce a new age-dependent model of the human lens with two GRIN power distributions (axial and radial) that allow decoupling of its refractive power and axial optical path length. The aspect ratio of the lens core can be held constant under accommodation, as well as the lens volume by varying the asphericity of the lens external surfaces. The spherical aberration calculated by exact raytracing is shown to be in line with experimental data. The proposed model is compared to previous GRIN models from the literature, and it is concluded that the features of the new model will be useful for GRIN reconstruction in future experimental studies; in particular, studies of the accommodation-dependent properties of the ageing human eye. A proposed logarithmic model of the lens core enables decoupling of three fundamental optical characteristics of the lens, namely axial optical path length, optical power and third-order spherical aberration, without changing the external shape of the lens. Conversely, the near-surface GRIN structure conforms to the external shape of the lens, which is necessary for accommodation modelling. PMID:27231637

  16. Optimal Harvesting in an Age-Structured Predator-Prey Model

    SciTech Connect

    Fister, K. Renee Lenhart, Suzanne

    2006-06-15

    We investigate optimal harvesting control in a predator-prey model in which the prey population is represented by a first-order partial differential equation with age-structure and the predator population is represented by an ordinary differential equation in time. The controls are the proportions of the populations to be harvested, and the objective functional represents the profit from harvesting. The existence and uniqueness of the optimal control pair are established.

  17. Generative FDG-PET and MRI model of aging and disease progression in Alzheimer's disease.

    PubMed

    Dukart, Juergen; Kherif, Ferath; Mueller, Karsten; Adaszewski, Stanislaw; Schroeter, Matthias L; Frackowiak, Richard S J; Draganski, Bogdan

    2013-04-01

    The failure of current strategies to provide an explanation for controversial findings on the pattern of pathophysiological changes in Alzheimer's Disease (AD) motivates the necessity to develop new integrative approaches based on multi-modal neuroimaging data that captures various aspects of disease pathology. Previous studies using [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and structural magnetic resonance imaging (sMRI) report controversial results about time-line, spatial extent and magnitude of glucose hypometabolism and atrophy in AD that depend on clinical and demographic characteristics of the studied populations. Here, we provide and validate at a group level a generative anatomical model of glucose hypo-metabolism and atrophy progression in AD based on FDG-PET and sMRI data of 80 patients and 79 healthy controls to describe expected age and symptom severity related changes in AD relative to a baseline provided by healthy aging. We demonstrate a high level of anatomical accuracy for both modalities yielding strongly age- and symptom-severity- dependant glucose hypometabolism in temporal, parietal and precuneal regions and a more extensive network of atrophy in hippocampal, temporal, parietal, occipital and posterior caudate regions. The model suggests greater and more consistent changes in FDG-PET compared to sMRI at earlier and the inversion of this pattern at more advanced AD stages. Our model describes, integrates and predicts characteristic patterns of AD related pathology, uncontaminated by normal age effects, derived from multi-modal data. It further provides an integrative explanation for findings suggesting a dissociation between early- and late-onset AD. The generative model offers a basis for further development of individualized biomarkers allowing accurate early diagnosis and treatment evaluation. PMID:23592957

  18. A new age model for the early-middle Miocene in the North Alpine Foreland Basin

    NASA Astrophysics Data System (ADS)

    Reichenbacher, Bettina; Krijgsman, Wout; Pippèrr, Martina; Sant, Karin; Kirscher, Uwe

    2016-04-01

    The establishment of high-resolution age models for sedimentary successions is crucial for numerous research questions in the geosciences and related disciplines. Such models provide an absolute chronology that permits precise dating of depositional episodes and related processes such as mountain uplift or climate change. Recently, our work in the Miocene sediments of the North Alpine Foreland Basin (NAFB) has revealed a significantly younger age (16.6 Myr) for sediments that were thought to have been deposited 18 Myr ago. This implies that a fundamentally revised new age model is needed for the entire suite of lower-middle Miocene sedimentary rocks in the NAFB (20 to 15-Myr). Our new data also indicate that previously published reconstructions of early-middle Miocene palaeogeography, sedimentation dynamics, mountain uplift and climate change in the NAFB all require a critical review and revision. Further, the time-span addressed is of special interest, since it encompasses the onset of a global warming phase. However, it appears that a fundamentally revised new age model for the entire suite of lower-middle Miocene sedimentary rocks in the NAFB can only be achieved based on a 500 m deep drilling in the NAFB for which we currently seek collaboration partners to develop a grant application to the International Continental Deep Drilling Program (ICDP). Reference: Reichenbacher, B., W. Krijgsman, Y. Lataster, M. Pippèrr, C. G. C. Van Baak, L. Chang, D. Kälin, J. Jost, G. Doppler, D. Jung, J. Prieto, H. Abdul Aziz, M. Böhme, J. Garnish, U. Kirscher, and V. Bachtadse. 2013. A new magnetostratigraphic framework for the Lower Miocene (Burdigalian/Ottnangian, Karpatian) in the North Alpine Foreland Basin. Swiss Journal of Geosciences 106:309-334.

  19. Epidemic spreading model to characterize misfolded proteins propagation in aging and associated neurodegenerative disorders.

    PubMed

    Iturria-Medina, Yasser; Sotero, Roberto C; Toussaint, Paule J; Evans, Alan C

    2014-11-01

    Misfolded proteins (MP) are a key component in aging and associated neurodegenerative disorders. For example, misfolded Amyloid-ß (Aß) and tau proteins are two neuropathogenic hallmarks of Alzheimer's disease. Mechanisms underlying intra-brain MP propagation/deposition remain essentially uncharacterized. Here, is introduced an epidemic spreading model (ESM) for MP dynamics that considers propagation-like interactions between MP agents and the brain's clearance response across the structural connectome. The ESM reproduces advanced Aß deposition patterns in the human brain (explaining 46∼56% of the variance in regional Aß loads, in 733 subjects from the ADNI database). Furthermore, this model strongly supports a) the leading role of Aß clearance deficiency and early Aß onset age during Alzheimer's disease progression, b) that effective anatomical distance from Aß outbreak region explains regional Aß arrival time and Aß deposition likelihood, c) the multi-factorial impact of APOE e4 genotype, gender and educational level on lifetime intra-brain Aß propagation, and d) the modulatory impact of Aß propagation history on tau proteins concentrations, supporting the hypothesis of an interrelated pathway between Aß pathophysiology and tauopathy. To our knowledge, the ESM is the first computational model highlighting the direct link between structural brain networks, production/clearance of pathogenic proteins and associated intercellular transfer mechanisms, individual genetic/demographic properties and clinical states in health and disease. In sum, the proposed ESM constitutes a promising framework to clarify intra-brain region to region transference mechanisms associated with aging and neurodegenerative disorders. PMID:25412207

  20. Epidemic Spreading Model to Characterize Misfolded Proteins Propagation in Aging and Associated Neurodegenerative Disorders

    PubMed Central

    Iturria-Medina, Yasser; Sotero, Roberto C.; Toussaint, Paule J.; Evans, Alan C.

    2014-01-01

    Misfolded proteins (MP) are a key component in aging and associated neurodegenerative disorders. For example, misfolded Amyloid-ß (Aß) and tau proteins are two neuropathogenic hallmarks of Alzheimer's disease. Mechanisms underlying intra-brain MP propagation/deposition remain essentially uncharacterized. Here, is introduced an epidemic spreading model (ESM) for MP dynamics that considers propagation-like interactions between MP agents and the brain's clearance response across the structural connectome. The ESM reproduces advanced Aß deposition patterns in the human brain (explaining 46∼56% of the variance in regional Aß loads, in 733 subjects from the ADNI database). Furthermore, this model strongly supports a) the leading role of Aß clearance deficiency and early Aß onset age during Alzheimer's disease progression, b) that effective anatomical distance from Aß outbreak region explains regional Aß arrival time and Aß deposition likelihood, c) the multi-factorial impact of APOE e4 genotype, gender and educational level on lifetime intra-brain Aß propagation, and d) the modulatory impact of Aß propagation history on tau proteins concentrations, supporting the hypothesis of an interrelated pathway between Aß pathophysiology and tauopathy. To our knowledge, the ESM is the first computational model highlighting the direct link between structural brain networks, production/clearance of pathogenic proteins and associated intercellular transfer mechanisms, individual genetic/demographic properties and clinical states in health and disease. In sum, the proposed ESM constitutes a promising framework to clarify intra-brain region to region transference mechanisms associated with aging and neurodegenerative disorders. PMID:25412207

  1. Modelling the climate, ice sheet and thermohaline circulation during the ice age termination

    NASA Astrophysics Data System (ADS)

    Abe-Ouchi, A.; Saito, F.; Kawamura, K.; Ohgaito, R.; Chikamoto, M. O.; Oka, A.; Yoshimori, M.; Yokoyama, Y.

    2009-12-01

    One of the challenges of earth system modeling is to explain the mechanism of ice age cycle by simulating it and to understand the uniqueness or necessity of the present state of climate and cryosphere. Whether Milankovitch cycle or CO2 is the driver and why the dominant periodicity of ice age cycle switched from 40 ka cycle to 100ka cycle and why a sharp termination occur for each ice age cycle have been remained unsolved. Here we simulate the glacial cycle and investigate the origin of saw-tooth shape 100ka cycle using a three dimensional ice sheet model with the input examined by GCM. The model is forced by the orbital parameters (Berger, 1978) and atmospheric CO2 content obtained by ice cores (Vostok, EPICA and DomeF), whose dating is partly given by a new method using the N2/O2 ratio. The ice sheet model includes the thermo-mechanical coupling process of ice sheet with the process of delayed isostatic rebound with a typical time constant. In order to estimate the climate sensitivity to Milankovitch forcing and atmospheric CO2 indicated by ice core data we used an atmospheric GCM (part of MIROC GCM) coupled to a slab ocean and full MIROC AOGCM in part of the work. Within the range of possibilities of the model, ice age cycles with a saw-tooth shape 100 ka cycle, the major NH ice sheets’ volume and the geographical distribution at the glacial maximum are successfully simulated. Moreover the role of Atmospheric stationary wave feedback are found to be important to sharpen the termination. It is shown by sensitivity studies that this 100ka cycle is mainly obtained by the slowly acting ice sheet response to Milankovitch forcing even without the CO2 cycle. The CO2 change amplifies the cycle and affects the global climate change, while the delay of crustal rebound sharpens the termination of every ice age cycle. In order to study the effect of thermohaline circulation, the sensitivity of AOGCM (by MIROC) is separately studied by applying time slice experiments of

  2. Ngram time series model to predict activity type and energy cost from wrist, hip and ankle accelerometers: implications of age

    PubMed Central

    Strath, Scott J; Kate, Rohit J; Keenan, Kevin G; Welch, Whitney A; Swartz, Ann M

    2016-01-01

    To develop and test time series single site and multi-site placement models, we used wrist, hip and ankle processed accelerometer data to estimate energy cost and type of physical activity in adults. Ninety-nine subjects in three age groups (18–39, 40–64, 65 + years) performed 11 activities while wearing three triaxial accelereometers: one each on the non-dominant wrist, hip, and ankle. During each activity net oxygen cost (METs) was assessed. The time series of accelerometer signals were represented in terms of uniformly discretized values called bins. Support Vector Machine was used for activity classification with bins and every pair of bins used as features. Bagged decision tree regression was used for net metabolic cost prediction. To evaluate model performance we employed the jackknife leave-one-out cross validation method. Single accelerometer and multi-accelerometer site model estimates across and within age group revealed similar accuracy, with a bias range of −0.03 to 0.01 METs, bias percent of −0.8 to 0.3%, and a rMSE range of 0.81–1.04 METs. Multi-site accelerometer location models improved activity type classification over single site location models from a low of 69.3% to a maximum of 92.8% accuracy. For each accelerometer site location model, or combined site location model, percent accuracy classification decreased as a function of age group, or when young age groups models were generalized to older age groups. Specific age group models on average performed better than when all age groups were combined. A time series computation show promising results for predicting energy cost and activity type. Differences in prediction across age group, a lack of generalizability across age groups, and that age group specific models perform better than when all ages are combined needs to be considered as analytic calibration procedures to detect energy cost and type are further developed. PMID:26449155

  3. Ngram time series model to predict activity type and energy cost from wrist, hip and ankle accelerometers: implications of age.

    PubMed

    Strath, Scott J; Kate, Rohit J; Keenan, Kevin G; Welch, Whitney A; Swartz, Ann M

    2015-11-01

    To develop and test time series single site and multi-site placement models, we used wrist, hip and ankle processed accelerometer data to estimate energy cost and type of physical activity in adults. Ninety-nine subjects in three age groups (18-39, 40-64, 65 +  years) performed 11 activities while wearing three triaxial accelereometers: one each on the non-dominant wrist, hip, and ankle. During each activity net oxygen cost (METs) was assessed. The time series of accelerometer signals were represented in terms of uniformly discretized values called bins. Support Vector Machine was used for activity classification with bins and every pair of bins used as features. Bagged decision tree regression was used for net metabolic cost prediction. To evaluate model performance we employed the jackknife leave-one-out cross validation method. Single accelerometer and multi-accelerometer site model estimates across and within age group revealed similar accuracy, with a bias range of -0.03 to 0.01 METs, bias percent of -0.8 to 0.3%, and a rMSE range of 0.81-1.04 METs. Multi-site accelerometer location models improved activity type classification over single site location models from a low of 69.3% to a maximum of 92.8% accuracy. For each accelerometer site location model, or combined site location model, percent accuracy classification decreased as a function of age group, or when young age groups models were generalized to older age groups. Specific age group models on average performed better than when all age groups were combined. A time series computation show promising results for predicting energy cost and activity type. Differences in prediction across age group, a lack of generalizability across age groups, and that age group specific models perform better than when all ages are combined needs to be considered as analytic calibration procedures to detect energy cost and type are further developed. PMID:26449155

  4. AGING MODEL FOR CANE FIBERBOARD OVERPACK IN THE 9975 SHIPPING PACKAGE

    SciTech Connect

    Daugherty, W.; Harris, S.

    2010-03-05

    Many radioactive material shipping packages incorporate a cane fiberboard overpack for thermal insulation and impact resistance. Mechanical, thermal and physical properties have been measured on cane fiberboard following thermal aging in several temperature/humidity environments. Several of the measured properties change significantly over time in the more severe environments, while other properties are relatively constant. Changes in each of the properties have been fit to a model to allow predictions of degradation under various storage scenarios. Additional data continue to be collected to provide for future refinements to the model.

  5. A stress-induced cellular aging model with postnatal neural stem cells.

    PubMed

    Dong, C-M; Wang, X-L; Wang, G-M; Zhang, W-J; Zhu, L; Gao, S; Yang, D-J; Qin, Y; Liang, Q-J; Chen, Y-L; Deng, H-T; Ning, K; Liang, A-B; Gao, Z-L; Xu, J

    2014-01-01

    Aging refers to the physical and functional decline of the tissues over time that often leads to age-related degenerative diseases. Accumulating evidence implicates that the senescence of neural stem cells (NSCs) is of paramount importance to the aging of central neural system (CNS). However, exploration of the underlying molecular mechanisms has been hindered by the lack of proper aging models to allow the mechanistic examination within a reasonable time window. In the present study, we have utilized a hydroxyurea (HU) treatment protocol and effectively induced postnatal subventricle NSCs to undergo cellular senescence as determined by augmented senescence-associated-β-galactosidase (SA-β-gal) staining, decreased proliferation and differentiation capacity, increased G0/G1 cell cycle arrest, elevated reactive oxygen species (ROS) level and diminished apoptosis. These phenotypic changes were accompanied by a significant increase in p16, p21 and p53 expression, as well as a decreased expression of key proteins in various DNA repair pathways such as xrcc2, xrcc3 and ku70. Further proteomic analysis suggests that multiple pathways are involved in the HU-induced NSC senescence, including genes related to DNA damage and repair, mitochondrial dysfunction and the increase of ROS level. Intriguingly, compensatory mechanisms may have also been initiated to interfere with apoptotic signaling pathways and to minimize the cell death by downregulating Bcl2-associated X protein (BAX) expression. Taken together, we have successfully established a cellular model that will be of broad utilities to the molecular exploration of NSC senescence and aging. PMID:24625975

  6. Effects of IMOD™ and Angipars™ on mouse D-galactose-induced model of aging

    PubMed Central

    2012-01-01

    The aim of this study was to evaluate the effects of two registered herbal drugs called IMOD and Angipars on mouse model. Aging was induced by D-galactose (500 mg/kg) administered to animals for 6 weeks through drinking water. Male BALB/c mice were randomly divided into 5 groups receiving D-galactose (D-galactose, 500 mg/kg) for 6 weeks; positive control (D-galactose [500 mg/kg] for 6 weeks + Vitamin E [200 mg/kg/day] intraperitoneally for 4 weeks); IMOD (D-galactose [500 mg/kg] for 6 weeks + IMOD [20 mg/kg/day] intraperitoneally for 4 weeks), Angipars (D-galactose [500 mg/kg] for 6 weeks + Angipars [2.1 mg/kg/day] by gavage for 4 weeks); and the fifth group that was sham and not given D-galactose. At the end of treatment, pro-inflammatory markers including tumor necrosis factor-α (TNF-α), interlukine-1β (IL-β), interlukine-6 (IL-6), Nuclear Factor-kappaB (NF-κb), total antioxidant power (TAP), lipid peroxides (LPO) and male sex hormones i.e. testosterone and dehydroepiandrosterone-sulfate (DHEA-S) were measured in the blood. Results showed that D-Galactose induces a significant oxidative stress and proinflammatory cascade of aging while both IMOD and Angipars recovered all of them. Interestingly, IMOD and Angipars were better than Vitamin E in improving male sex hormones in aged mice. This effect is so important and should be considered as an advantage although it cannot be explained with current knowledge. The conclusion is that IMOD and Angipars have marked anti-aging effect on D-galactose-induced model of aging. PMID:23351487

  7. Effects of IMOD™ and Angipars™ on mouse D-galactose-induced model of aging.

    PubMed

    Ghanbari, Samane; Yonessi, Mahsa; Mohammadirad, Azadeh; Gholami, Mahdi; Baeeri, Maryam; Khorram-Khorshid, Hamid Reza; Gharibdoost, Farhad; Abdollahi, Mohammad

    2012-01-01

    The aim of this study was to evaluate the effects of two registered herbal drugs called IMOD and Angipars on mouse model. Aging was induced by D-galactose (500 mg/kg) administered to animals for 6 weeks through drinking water. Male BALB/c mice were randomly divided into 5 groups receiving D-galactose (D-galactose, 500 mg/kg) for 6 weeks; positive control (D-galactose [500 mg/kg] for 6 weeks + Vitamin E [200 mg/kg/day] intraperitoneally for 4 weeks); IMOD (D-galactose [500 mg/kg] for 6 weeks + IMOD [20 mg/kg/day] intraperitoneally for 4 weeks), Angipars (D-galactose [500 mg/kg] for 6 weeks + Angipars [2.1 mg/kg/day] by gavage for 4 weeks); and the fifth group that was sham and not given D-galactose. At the end of treatment, pro-inflammatory markers including tumor necrosis factor-α (TNF-α), interlukine-1β (IL-β), interlukine-6 (IL-6), Nuclear Factor-kappaB (NF-κb), total antioxidant power (TAP), lipid peroxides (LPO) and male sex hormones i.e. testosterone and dehydroepiandrosterone-sulfate (DHEA-S) were measured in the blood.Results showed that D-Galactose induces a significant oxidative stress and proinflammatory cascade of aging while both IMOD and Angipars recovered all of them. Interestingly, IMOD and Angipars were better than Vitamin E in improving male sex hormones in aged mice. This effect is so important and should be considered as an advantage although it cannot be explained with current knowledge. The conclusion is that IMOD and Angipars have marked anti-aging effect on D-galactose-induced model of aging. PMID:23351487

  8. Aging into Perceptual Control: A Dynamic Causal Modeling for fMRI Study of Bistable Perception

    PubMed Central

    Dowlati, Ehsan; Adams, Sarah E.; Stiles, Alexandra B.; Moran, Rosalyn J.

    2016-01-01

    Aging is accompanied by stereotyped changes in functional brain activations, for example a cortical shift in activity patterns from posterior to anterior regions is one hallmark revealed by functional magnetic resonance imaging (fMRI) of aging cognition. Whether these neuronal effects of aging could potentially contribute to an amelioration of or resistance to the cognitive symptoms associated with psychopathology remains to be explored. We used a visual illusion paradigm to address whether aging affects the cortical control of perceptual beliefs and biases. Our aim was to understand the effective connectivity associated with volitional control of ambiguous visual stimuli and to test whether greater top-down control of early visual networks emerged with advancing age. Using a bias training paradigm for ambiguous images we found that older participants (n = 16) resisted experimenter-induced visual bias compared to a younger cohort (n = 14) and that this resistance was associated with greater activity in prefrontal and temporal cortices. By applying Dynamic Causal Models for fMRI we uncovered a selective recruitment of top-down connections from the middle temporal to Lingual gyrus (LIN) by the older cohort during the perceptual switch decision following bias training. In contrast, our younger cohort did not exhibit any consistent connectivity effects but instead showed a loss of driving inputs to orbitofrontal sources following training. These findings suggest that perceptual beliefs are more readily controlled by top-down strategies in older adults and introduce age-dependent neural mechanisms that may be important for understanding aberrant belief states associated with psychopathology. PMID:27064235

  9. The problem of calibration: A possible way to overcome the drawbacks of age models

    NASA Astrophysics Data System (ADS)

    Goswami, B.; Heitzig, J.; Rehfeld, K.; Marwan, N.; Kurths, J.

    2012-04-01

    Constructing a meaningful age model from a set of radiocarbon age-depth measurements made on a palaeoclimatic archive is the crucial backbone of all proxy-based research carried out thereafter. Significant progress in the development of Monte Carlo based interpolation techniques and Bayesian methods has been made recently, targeting the uncertainties of radiocarbon dating, which then reflect meaningfully as time domain errors in the proxy vs. time relationship. However, one primary limitation of these approaches is the debatable assumption of Gaussianity of the errors in calibrated ages as calibration often results in highly irregular and non-trivial probability distributions of the age for every measurement. Here, we present a method that circumvents this limitation by focussing on the construction of the proxy vs. time relationship rather than emphasising on the estimation of an age-depth relation as the intermediary step. Our method is based on a simple analysis of the involved probabilistic uncertainties and the use of (preferably non-parametric) regression methods that give an estimate of the uncertainty of regression at every point as well. With the appropriate use of Bayes' Theorem we then provide a regression-based estimator for the proxy measurements and compute the respective distribution parameters (such as mean and variance) that quantify the uncertainties of the proxy in the time domain. We verify this method with the help of an artificial data set involving the accumulation history of a simulated core and noisy radiocarbon dating and proxy measurements made on it. To our best knowledge, this is the first method that manages to overcome the fundamental problem of irregular distributions induced by calibration of radiocarbon ages. We feel that this approach shall enable us to look at the problem of dating uncertainties in a new light and open up newer possibilities for studying not only speleothem proxies but, more generally, from other palaeoclimatic

  10. Probabilistic graphical models to deal with age estimation of living persons.

    PubMed

    Sironi, Emanuele; Gallidabino, Matteo; Weyermann, Céline; Taroni, Franco

    2016-03-01

    Due to the rise of criminal, civil and administrative judicial situations involving people lacking valid identity documents, age estimation of living persons has become an important operational procedure for numerous forensic and medicolegal services worldwide. The chronological age of a given person is generally estimated from the observed degree of maturity of some selected physical attributes by means of statistical methods. However, their application in the forensic framework suffers from some conceptual and practical drawbacks, as recently claimed in the specialised literature. The aim of this paper is therefore to offer an alternative solution for overcoming these limits, by reiterating the utility of a probabilistic Bayesian approach for age estimation. This approach allows one to deal in a transparent way with the uncertainty surrounding the age estimation process and to produce all the relevant information in the form of posterior probability distribution about the chronological age of the person under investigation. Furthermore, this probability distribution can also be used for evaluating in a coherent way the possibility that the examined individual is younger or older than a given legal age threshold having a particular legal interest. The main novelty introduced by this work is the development of a probabilistic graphical model, i.e. a Bayesian network, for dealing with the problem at hand. The use of this kind of probabilistic tool can significantly facilitate the application of the proposed methodology: examples are presented based on data related to the ossification status of the medial clavicular epiphysis. The reliability and the advantages of this probabilistic tool are presented and discussed. PMID:25794687

  11. Dysregulation of mitochondrial quality control processes contribute to sarcopenia in a mouse model of premature aging.

    PubMed

    Joseph, Anna-Maria; Adhihetty, Peter J; Wawrzyniak, Nicholas R; Wohlgemuth, Stephanie E; Picca, Anna; Kujoth, Gregory C; Prolla, Tomas A; Leeuwenburgh, Christiaan

    2013-01-01

    Mitochondrial DNA (mtDNA) mutations lead to decrements in mitochondrial function and accelerated rates of these mutations has been linked to skeletal muscle loss (sarcopenia). The purpose of this study was to investigate the effect of mtDNA mutations on mitochondrial quality control processes in skeletal muscle from animals (young; 3-6 months and older; 8-15 months) expressing a proofreading-deficient version of mtDNA polymerase gamma (PolG). This progeroid aging model exhibits elevated mtDNA mutation rates, mitochondrial dysfunction, and a premature aging phenotype that includes sarcopenia. We found increased expression of the mitochondrial biogenesis regulator peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and its target proteins, nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (Tfam) in PolG animals compared to wild-type (WT) (P<0.05). Muscle from older PolG animals displayed higher mitochondrial fission protein 1 (Fis1) concurrent with greater induction of autophagy, as indicated by changes in Atg5 and p62 protein content (P<0.05). Additionally, levels of the Tom22 import protein were higher in PolG animals when compared to WT (P<0.05). In contrast, muscle from normally-aged animals exhibited a distinctly different expression profile compared to PolG animals. Older WT animals appeared to have higher fusion (greater Mfn1/Mfn2, and lower Fis1) and lower autophagy (Beclin-1 and p62) compared to young WT suggesting that autophagy is impaired in aging muscle. In conclusion, muscle from mtDNA mutator mice display higher mitochondrial fission and autophagy levels that likely contribute to the sarcopenic phenotype observed in premature aging and this differs from the response observed in normally-aged muscle. PMID:23935986

  12. Biological Effects Induced by Specific Advanced Glycation End Products in the Reconstructed Skin Model of Aging.

    PubMed

    Pageon, Hervé; Zucchi, Hélène; Dai, Zhenyu; Sell, David R; Strauch, Christopher M; Monnier, Vincent M; Asselineau, Daniel

    2015-01-01

    Advanced glycation end products (AGEs) accumulate in the aging skin. To understand the biological effects of individual AGEs, skin reconstructed with collagen selectively enriched with N(ɛ)-(carboxymethyl)-lysine (CML), N(ɛ)-(carboxyethyl)-lysine (CEL), methylglyoxal hydroimidazolone (MG-H1), or pentosidine was studied. Immunohistochemistry revealed increased expression of α6 integrin at the dermal epidermal junction by CEL and CML (p<0.01). Laminin 5 was diminished by CEL and MG-H1 (p<0.05). Both CML and CEL induced a robust increase (p<0.01) in procollagen I. In the culture medium, IL-6, VEGF, and MMP1 secretion were significantly decreased (p<0.05) by MG-H1. While both CEL and CML decreased MMP3, only CEL decreased IL-6 and TIMP1, while CML stimulated TIMP1 synthesis significantly (p<0.05). mRNA expression studies using qPCR in the epidermis layer showed that CEL increased type 7 collagen (COL7A1), β1, and α6 integrin, while CML increased only COL7A1 (p<0.05). MG-H1-modified collagen had no effect. Importantly, in the dermis layer, MMP3 mRNA expression was increased by both CML and MG-H1. CML also significantly increased the mRNAs of MMP1, TIMP1, keratinocyte growth factor (KGF), IL-6, and monocyte chemoattractant protein 1 (MCP1) (p<0.05). Mixed effects were present in CEL-rich matrix. Minimally glycoxidized pentosidine-rich collagen suppressed most mRNAs of the genes studied (p<0.05) and decreased VEGF and increased MCP1 protein expression. Taken together, this model of the aging skin suggests that a combination of AGEs tends to counterbalance and thus minimizes the detrimental biological effects of individual AGEs. PMID:26309782

  13. Preparing the Workforce for Healthy Aging Programs: The Skills for Healthy Aging Resources and Programs (SHARP) Model

    ERIC Educational Resources Information Center

    Frank, Janet C.; Altpeter, Mary; Damron-Rodriguez, JoAnn; Driggers, Joann; Lachenmayr, Susan; Manning, Colleen; Martinez, Dana M.; Price, Rachel M.; Robinson, Patricia

    2014-01-01

    Current public health and aging service agency personnel have little training in gerontology, and virtually no training in evidence-based health promotion and disease management programs for older adults. These programs are rapidly becoming the future of our community-based long-term care support system. The purpose of this project was to develop…

  14. The Role of a Model's Age for Young Children's Imitation: A Research Review

    ERIC Educational Resources Information Center

    Zmyj, Norbert; Seehagen, Sabine

    2013-01-01

    The influence of a model's age on young children's behaviour has been a subject of considerable debate among developmental theorists. Despite the recent surge of interest, controversy remains about the nature of peer influence in early life. This article reviews studies that investigated the influence of a model's age on young…

  15. Models for preclinical studies in aging-related disorders: One is not for all

    PubMed Central

    Santulli, Gaetano; Borras, Consuelo; Bousquet, Jean; Calzà, Laura; Cano, Antonio; Illario, Maddalena; Franceschi, Claudio; Liotta, Giuseppe; Maggio, Marcello; Molloy, William D.; Montuori, Nunzia; O’Caoimh, Rónán; Orfila, Francesc; Rauter, Amelia P.; Santoro, Aurelia; Iaccarino, Guido

    2015-01-01

    Preclinical studies are essentially based on animal models of a particular disease. The primary purpose of preclinical efficacy studies is to support generalization of treatment–effect relationships to human subjects. Researchers aim to demonstrate a causal relationship between an investigational agent and a disease-related phenotype in such models. Numerous factors can muddle reliable inferences about such cause-effect relationships, including biased outcome assessment due to experimenter expectations. For instance, responses in a particular inbred mouse might be specific to the strain, limiting generalizability. Selecting well-justified and widely acknowledged model systems represents the best start in designing preclinical studies, especially to overcome any potential bias related to the model itself. This is particularly true in the research that focuses on aging, which carries unique challenges, mainly attributable to the fact that our already long lifespan makes designing experiments that use people as subjects extremely difficult and largely impractical. PMID:27042427

  16. Influence of Age on Ocular Biomechanical Properties in a Canine Glaucoma Model with ADAMTS10 Mutation

    PubMed Central

    Palko, Joel R.; Morris, Hugh J.; Pan, Xueliang; Harman, Christine D.; Koehl, Kristin L.; Gelatt, Kirk N.; Plummer, Caryn E.; Komáromy, András M.; Liu, Jun

    2016-01-01

    Soft tissue often displays marked age-associated stiffening. This study aims to investigate how age affects scleral biomechanical properties in a canine glaucoma model with ADAMTS10 mutation, whose extracellular matrix is concomitantly influenced by the mutation and an increased mechanical load from an early age. Biomechanical data was acquired from ADAMTS10-mutant dogs (n = 10, 21 to 131 months) and normal dogs (n = 5, 69 to 113 months). Infusion testing was first performed in the whole globes to measure ocular rigidity. After infusion experiments, the corneas were immediately trephined to prepare scleral shells that were mounted on a pressurization chamber to measure strains in the posterior sclera using an inflation testing protocol. Dynamic viscoelastic mechanical testing was then performed on dissected posterior scleral strips and the data were combined with those reported earlier by our group from the same animal model (Palko et al, IOVS 2013). The association between age and scleral biomechanical properties was evaluated using multivariate linear regression. The relationships between scleral properties and the mean and last measured intraocular pressure (IOP) were also evaluated. Our results showed that age was positively associated with complex modulus (p<0.001) and negatively associated with loss tangent (p<0.001) in both the affected and the normal groups, suggesting an increased stiffness and decreased mechanical damping with age. The regression slopes were not different between the groups, although the complex modulus was significantly lower in the affected group (p = 0.041). The posterior circumferential tangential strain was negatively correlated with complex modulus (R = -0.744, p = 0.006) showing consistent mechanical evaluation between the testing methods. Normalized ocular rigidity was negatively correlated with the last IOP in the affected group (p = 0.003). Despite a mutation that affects the extracellular matrix and a chronic IOP elevation in

  17. Modeling 3H-3He Gas-Liquid Phase Transport for Interpretation of Groundwater Age

    NASA Astrophysics Data System (ADS)

    Carle, S. F.; Esser, B.; Moran, J. E.

    2009-12-01

    California’s Groundwater Ambient Monitoring and Assessment (GAMA) Program has measured many hundreds of tritium (3H) and helium-3 (3He) concentrations in well water samples to derive estimates of groundwater age at production and monitoring wells in California basins. However, a 3H-3He age differs from an ideal groundwater age tracer in several respects: (1) the radioactive decay of 3H results in the accumulation of 3He being first-order with respect to 3H activity (versus a zero-order age-mass accumulation process for an ideal tracer), (2) surface concentrations of 3H as measured in precipitation over the last several decades have not been uniform, and (3) the 3H-3He “clock” begins at the water table and not at the ground surface where 3H source measurements are made. To better understand how these non-idealities affect interpretation of 3H-3He apparent groundwater age, we are modeling coupled gas-liquid phase flow and 3H-3He transport including processes of radiogenic decay, phase equilibrium, and molecular diffusion for water, air, 3H, and 3He components continuously through the vadose zone and saturated zone. Assessment of coupled liquid-gas phase processes enables consideration of 3H-3He residence time and dispersion within the vadose zone, including partitioning of tritiogenic 3He to the gas phase and subsequent diffusion into the atmosphere. The coupled gas-liquid phase modeling framework provides direct means to compare apparent 3H-3He age to ideal mean or advective groundwater ages for the same groundwater flow conditions. Examples are given for common groundwater flow systems involving areal recharge, discharge to streams or long-screened wells, and aquifer system heterogeneity. The Groundwater Ambient Monitoring and Assessment program is sponsored by the California State Water Resources Control Board and carried out in cooperation with the U.S. Geological Survey. This work was performed under the auspices of the U.S. Department of Energy by

  18. A Ternary Age-Mixing Model to Explain Contaminant Occurrence in a Deep Supply Well

    PubMed Central

    Jurgens, Bryant C; Bexfield, Laura M; Eberts, Sandra M

    2014-01-01

    The age distribution of water from a public-supply well in a deep alluvial aquifer was estimated and used to help explain arsenic variability in the water. The age distribution was computed using a ternary mixing model that combines three lumped parameter models of advection-dispersion transport of environmental tracers, which represent relatively recent recharge (post-1950s) containing volatile organic compounds (VOCs), old intermediate depth groundwater (about 6500 years) that was free of drinking-water contaminants, and very old, deep groundwater (more than 21,000 years) containing arsenic above the USEPA maximum contaminant level of 10 µg/L. The ternary mixing model was calibrated to tritium, chloroflorocarbon-113, and carbon-14 (14C) concentrations that were measured in water samples collected on multiple occasions. Variability in atmospheric 14C over the past 50,000 years was accounted for in the interpretation of 14C as a tracer. Calibrated ternary models indicate the fraction of deep, very old groundwater entering the well varies substantially throughout the year and was highest following long periods of nonoperation or infrequent operation, which occured during the winter season when water demand was low. The fraction of young water entering the well was about 11% during the summer when pumping peaked to meet water demand and about 3% to 6% during the winter months. This paper demonstrates how collection of multiple tracers can be used in combination with simplified models of fluid flow to estimate the age distribution and thus fraction of contaminated groundwater reaching a supply well under different pumping conditions. PMID:24597520

  19. A ternary age-mixing model to explain contaminant occurrence in a deep supply well

    USGS Publications Warehouse

    Jurgens, Bryant; Bexfield, Laura M.; Eberts, Sandra

    2014-01-01

    The age distribution of water from a public-supply well in a deep alluvial aquifer was estimated and used to help explain arsenic variability in the water. The age distribution was computed using a ternary mixing model that combines three lumped parameter models of advection-dispersion transport of environmental tracers, which represent relatively recent recharge (post- 1950s) containing volatile organic compounds (VOCs), old intermediate depth groundwater (about 6500 years) that was free of drinking-water contaminants, and very old, deep groundwater (more than 21,000 years) containing arsenic above the USEPA maximum contaminant level of 10 µg/L. The ternary mixing model was calibrated to tritium, chloroflorocarbon-113, and carbon-14 (14C) concentrations that were measured in water samples collected on multiple occasions. Variability in atmospheric 14C over the past 50,000 years was accounted for in the interpretation of 14C as a tracer. Calibrated ternary models indicate the fraction of deep, very old groundwater entering the well varies substantially throughout the year and was highest following long periods of nonoperation or infrequent operation, which occured during the winter season when water demand was low. The fraction of young water entering the well was about 11% during the summer when pumping peaked to meet water demand and about 3% to 6% during the winter months. This paper demonstrates how collection of multiple tracers can be used in combination with simplified models of fluid flow to estimate the age distribution and thus fraction of contaminated groundwater reaching a supply well under different pumping conditions.

  20. Transit times and age distributions for reservoir models represented as nonlinear non-autonomuous systems

    NASA Astrophysics Data System (ADS)

    Müller, Markus; Meztler, Holger; Glatt, Anna; Sierra, Carlos

    2016-04-01

    We present theoretical methods to compute dynamic residence and transit time distributions for non-autonomous systems of pools governed by coupled nonlinear differential equations. Although transit time and age distributions have been used to describe reservoir models for a long time, a closer look to their assumptions reveals two major restrictions of generality in previous studies. First, the systems are assumed to be in equilibrium; and second, the equations under consideration are assumed to be linear. While both these assumptions greatly ease the computation and interpretation of transit time and age distributions they are not applicable to a wide range of problems. Moreover, the transfer of previous results learned from linear systems in steady state to the more complex nonlinear non-autonomous systems that do not even need to have equilibria, can be dangerously misleading. Fortunately the topic of time dependent age and transit time distributions has received some attention recently in hydrology, we aim to compute these distributions for systems of multiple reservoirs. We will discuss how storage selection functions can augment the information represented in an ODE system describing a system of reservoirs. We will present analytical and numerical algorithms and a Monte Carlo simulator to compute solutions for system transit time and age distributions for system-wide storage selection functions including the most simple, but important case of well mixed pools.

  1. Aging Face Recognition: A Hierarchical Learning Model Based on Local Patterns Selection.

    PubMed

    Li, Zhifeng; Gong, Dihong; Li, Xuelong; Tao, Dacheng

    2016-05-01

    Aging face recognition refers to matching the same person's faces across different ages, e.g., matching a person's older face to his (or her) younger one, which has many important practical applications, such as finding missing children. The major challenge of this task is that facial appearance is subject to significant change during the aging process. In this paper, we propose to solve the problem with a hierarchical model based on two-level learning. At the first level, effective features are learned from low-level microstructures, based on our new feature descriptor called local pattern selection (LPS). The proposed LPS descriptor greedily selects low-level discriminant patterns in a way, such that intra-user dissimilarity is minimized. At the second level, higher level visual information is further refined based on the output from the first level. To evaluate the performance of our new method, we conduct extensive experiments on the MORPH data set (the largest face aging data set available in the public domain), which show a significant improvement in accuracy over the state-of-the-art methods. PMID:26930681

  2. Oxidative Stress and Protein Quality Control Systems in the Aged Canine Brain as a Model for Human Neurodegenerative Disorders

    PubMed Central

    2015-01-01

    Aged dogs are considered the most suitable spontaneous animal model for studying normal aging and neurodegenerative diseases. Elderly canines naturally develop cognitive dysfunction and neuropathological hallmarks similar to those seen in humans, especially Alzheimer's disease-like pathology. Pet dogs also share similar living conditions and diets to humans. Oxidative damage accumulates in the canine brain during aging, making dogs a valid model for translational antioxidant treatment/prevention studies. Evidence suggests the presence of detective protein quality control systems, involving ubiquitin-proteasome system (UPS) and Heat Shock Proteins (HSPs), in the aged canine brain. Further studies on the canine model are needed to clarify the role of age-related changes in UPS activity and HSP expression in neurodegeneration in order to design novel treatment strategies, such as HSP-based therapies, aimed at improving chaperone defences against proteotoxic stress affecting brain during aging. PMID:26078824

  3. Modeling the Mechanical Consequences of Age-Related Trabecular Bone Loss by XFEM Simulation

    PubMed Central

    Fan, Ruoxun; Zhang, Xianbin; Liu, Jun; Jia, Zhengbin; Zhu, Dong

    2016-01-01

    The elderly are more likely to suffer from fracture because of age-related trabecular bone loss. Different bone loss locations and patterns have different effects on bone mechanical properties. Extended finite element method (XFEM) can simulate fracture process and was suited to investigate the effects of bone loss on trabecular bone. Age-related bone loss is indicated by trabecular thinning and loss and may occur at low-strain locations or other random sites. Accordingly, several ideal normal and aged trabecular bone models were created based on different bone loss locations and patterns; then, fracture processes from crack initiation to complete failure of these models were observed by XFEM; finally, the effects of different locations and patterns on trabecular bone were compared. Results indicated that bone loss occurring at low-strain locations was more detrimental to trabecular bone than that occurring at other random sites; meanwhile, the decrease in bone strength caused by trabecular loss was higher than that caused by trabecular thinning, and the effects of vertical trabecular loss on mechanical properties were more severe than horizontal trabecular loss. This study provided a numerical method to simulate trabecular bone fracture and distinguished different effects of the possible occurrence of bone loss locations and patterns on trabecular bone. PMID:27403206

  4. Modeling the Mechanical Consequences of Age-Related Trabecular Bone Loss by XFEM Simulation.

    PubMed

    Fan, Ruoxun; Gong, He; Zhang, Xianbin; Liu, Jun; Jia, Zhengbin; Zhu, Dong

    2016-01-01

    The elderly are more likely to suffer from fracture because of age-related trabecular bone loss. Different bone loss locations and patterns have different effects on bone mechanical properties. Extended finite element method (XFEM) can simulate fracture process and was suited to investigate the effects of bone loss on trabecular bone. Age-related bone loss is indicated by trabecular thinning and loss and may occur at low-strain locations or other random sites. Accordingly, several ideal normal and aged trabecular bone models were created based on different bone loss locations and patterns; then, fracture processes from crack initiation to complete failure of these models were observed by XFEM; finally, the effects of different locations and patterns on trabecular bone were compared. Results indicated that bone loss occurring at low-strain locations was more detrimental to trabecular bone than that occurring at other random sites; meanwhile, the decrease in bone strength caused by trabecular loss was higher than that caused by trabecular thinning, and the effects of vertical trabecular loss on mechanical properties were more severe than horizontal trabecular loss. This study provided a numerical method to simulate trabecular bone fracture and distinguished different effects of the possible occurrence of bone loss locations and patterns on trabecular bone. PMID:27403206

  5. Bias in the reporting of sex and age in biomedical research on mouse models.

    PubMed

    Flórez-Vargas, Oscar; Brass, Andy; Karystianis, George; Bramhall, Michael; Stevens, Robert; Cruickshank, Sheena; Nenadic, Goran

    2016-01-01

    In animal-based biomedical research, both the sex and the age of the animals studied affect disease phenotypes by modifying their susceptibility, presentation and response to treatment. The accurate reporting of experimental methods and materials, including the sex and age of animals, is essential so that other researchers can build on the results of such studies. Here we use text mining to study 15,311 research papers in which mice were the focus of the study. We find that the percentage of papers reporting the sex and age of mice has increased over the past two decades: however, only about 50% of the papers published in 2014 reported these two variables. We also compared the quality of reporting in six preclinical research areas and found evidence for different levels of sex-bias in these areas: the strongest male-bias was observed in cardiovascular disease models and the strongest female-bias was found in infectious disease models. These results demonstrate the ability of text mining to contribute to the ongoing debate about the reproducibility of research, and confirm the need to continue efforts to improve the reporting of experimental methods and materials. PMID:26939790

  6. Bias in the reporting of sex and age in biomedical research on mouse models

    PubMed Central

    Flórez-Vargas, Oscar; Brass, Andy; Karystianis, George; Bramhall, Michael; Stevens, Robert; Cruickshank, Sheena; Nenadic, Goran

    2016-01-01

    In animal-based biomedical research, both the sex and the age of the animals studied affect disease phenotypes by modifying their susceptibility, presentation and response to treatment. The accurate reporting of experimental methods and materials, including the sex and age of animals, is essential so that other researchers can build on the results of such studies. Here we use text mining to study 15,311 research papers in which mice were the focus of the study. We find that the percentage of papers reporting the sex and age of mice has increased over the past two decades: however, only about 50% of the papers published in 2014 reported these two variables. We also compared the quality of reporting in six preclinical research areas and found evidence for different levels of sex-bias in these areas: the strongest male-bias was observed in cardiovascular disease models and the strongest female-bias was found in infectious disease models. These results demonstrate the ability of text mining to contribute to the ongoing debate about the reproducibility of research, and confirm the need to continue efforts to improve the reporting of experimental methods and materials. DOI: http://dx.doi.org/10.7554/eLife.13615.001 PMID:26939790

  7. Optimizing a Male Reproductive Aging Mouse Model by d-Galactose Injection

    PubMed Central

    Liao, Chun-Hou; Chen, Bing-Huei; Chiang, Han-Sun; Chen, Chiu-Wei; Chen, Mei-Feng; Ke, Chih-Chun; Wang, Ya-Yun; Lin, Wei-Ning; Wang, Chi-Chung; Lin, Ying-Hung

    2016-01-01

    The d-galactose (d-gal)-injected animal model, which is typically established by administering consecutive subcutaneous d-gal injections to animals for approximately six or eight weeks, has been frequently used for aging research. In addition, this animal model has been demonstrated to accelerate aging in the brain, kidneys, liver and blood cells. However, studies on aging in male reproductive organs that have used this animal model remain few. Therefore, the current study aimed to optimize a model of male reproductive aging by administering d-gal injections to male mice and to determine the possible mechanism expediting senescence processes during spermatogenesis. In this study, C57Bl/6 mice were randomized into five groups (each containing 8–10 mice according to the daily intraperitoneal injection of vehicle control or 100 or 200 mg/kg dosages of d-gal for a period of six or eight weeks). First, mice subjected to d-gal injections for six or eight weeks demonstrated considerably decreased superoxide dismutase activity in the serum and testis lysates compared to those in the control group. The lipid peroxidation in testis also increased in the d-gal-injected groups. Furthermore, the d-gal-injected groups exhibited a decreased ratio of testis weight/body weight and sperm count compared to the control group. The percentages of both immotile sperm and abnormal sperm increased considerably in the d-gal-injected groups compared to those of the control group. To determine the genes influenced by the d-gal injection during murine spermatogenesis, a c-DNA microarray was conducted to compare testicular RNA samples between the treated groups and the control group. The d-gal-injected groups exhibited RNA transcripts of nine spermatogenesis-related genes (Cycl2, Hk1, Pltp, Utp3, Cabyr, Zpbp2, Speer2, Csnka2ip and Katnb1) that were up- or down-regulated by at least two-fold compared to the control group. Several of these genes are critical for forming sperm-head morphologies

  8. Optimizing a Male Reproductive Aging Mouse Model by D-Galactose Injection.

    PubMed

    Liao, Chun-Hou; Chen, Bing-Huei; Chiang, Han-Sun; Chen, Chiu-Wei; Chen, Mei-Feng; Ke, Chih-Chun; Wang, Ya-Yun; Lin, Wei-Ning; Wang, Chi-Chung; Lin, Ying-Hung

    2016-01-01

    The d-galactose (d-gal)-injected animal model, which is typically established by administering consecutive subcutaneous d-gal injections to animals for approximately six or eight weeks, has been frequently used for aging research. In addition, this animal model has been demonstrated to accelerate aging in the brain, kidneys, liver and blood cells. However, studies on aging in male reproductive organs that have used this animal model remain few. Therefore, the current study aimed to optimize a model of male reproductive aging by administering d-gal injections to male mice and to determine the possible mechanism expediting senescence processes during spermatogenesis. In this study, C57Bl/6 mice were randomized into five groups (each containing 8-10 mice according to the daily intraperitoneal injection of vehicle control or 100 or 200 mg/kg dosages of d-gal for a period of six or eight weeks). First, mice subjected to d-gal injections for six or eight weeks demonstrated considerably decreased superoxide dismutase activity in the serum and testis lysates compared to those in the control group. The lipid peroxidation in testis also increased in the d-gal-injected groups. Furthermore, the d-gal-injected groups exhibited a decreased ratio of testis weight/body weight and sperm count compared to the control group. The percentages of both immotile sperm and abnormal sperm increased considerably in the d-gal-injected groups compared to those of the control group. To determine the genes influenced by the d-gal injection during murine spermatogenesis, a c-DNA microarray was conducted to compare testicular RNA samples between the treated groups and the control group. The d-gal-injected groups exhibited RNA transcripts of nine spermatogenesis-related genes (Cycl2, Hk1, Pltp, Utp3, Cabyr, Zpbp2, Speer2, Csnka2ip and Katnb1) that were up- or down-regulated by at least two-fold compared to the control group. Several of these genes are critical for forming sperm-head morphologies or

  9. A mathematical model of physiological processes and its application to the study of aging

    NASA Technical Reports Server (NTRS)

    Hibbs, A. R.; Walford, R. L.

    1989-01-01

    The behavior of a physiological system which, after displacement, returns by homeostatic mechanisms to its original condition can be described by a simple differential equation in which the "recovery time" is a parameter. Two such systems, which influence one another, can be linked mathematically by the use of "coupling" or "feedback" coefficients. These concepts are the basis for many mathematical models of physiological behavior, and we describe the general nature of such models. Next, we introduce the concept of a "fatal limit" for the displacement of a physiological system, and show how measures of such limits can be included in mathematical models. We show how the numerical values of such limits depend on the values of other system parameters, i.e., recovery times and coupling coefficients, and suggest ways of measuring all these parameters experimentally, for example by monitoring changes induced by X-irradiation. Next, we discuss age-related changes in these parameters, and show how the parameters of mortality statistics, such as the famous Gompertz parameters, can be derived from experimentally measurable changes. Concepts of onset-of-aging, critical or fatal limits, equilibrium value (homeostasis), recovery times and coupling constants are involved. Illustrations are given using published data from mouse and rat populations. We believe that this method of deriving survival patterns from model that is experimentally testable is unique.

  10. ISSLS PRIZE WINNER: INHIBITION OF NF-κB ACTIVITY AMELIORATES AGE-ASSOCIATED DISC DEGENERATION IN A MOUSE MODEL OF ACCELERATED AGING

    PubMed Central

    Nasto, Luigi A.; Seo, Hyoung-Yeon; Robinson, Andria R.; Tilstra, Jeremy S.; Clauson, Cheryl L.; Sowa, Gwendolyn A.; Ngo, Kevin; Dong, Qing; Pola, Enrico; Lee, Joon Y.; Niedernhofer, Laura J.; Kang, James D.; Robbins, Paul D.; Vo, Nam V.

    2012-01-01

    Study Design NF-κB activity was pharmacologically and genetically blocked in an accelerated aging mouse model to mitigate age-related disc degenerative changes. Objective To study the mediatory role of NF-κB signaling pathway in age-dependent intervertebral disc degeneration. Summary of Background Data Aging is a major contributor to intervertebral disc degeneration (IDD), but the molecular mechanism behind this process is poorly understood. NF-κB is a family of transcription factors which play a central role in mediating cellular response to damage, stress, and inflammation. Growing evidence implicates chronic NF-κB activation as a culprit in many aging-related diseases, but its role in aging-related IDD has not been adequately explored. We studied the effects of NF-κB inhibition on IDD using a DNA repair-deficient mouse model of accelerated aging (Ercc1-/Δ mice) previously been reported to exhibit age-related IDD. Methods Systemic inhibition of NF-κB activation was achieved either genetically by deletion of one allele of the NF-κB subunit p65 (Ercc1-/Δp65+/- mice) or pharmacologically by chronic intra-peritoneal administration of the Nemo Binding Domain (8K-NBD) peptide to block the formation of the upstream activator of NF-κB, IκB Inducible Kinase (IKK), in Ercc1-/Δ mice. Disc cellularity, total proteoglycan content and proteoglycan synthesis of treated mice and untreated controls were assessed. Results Decreased disc matrix proteoglycan content, a hallmark feature of IDD, and elevated disc NF-κB activity were observed in discs of progeroid Ercc1-/Δ mice and naturally aged wild-type compared to young WT mice. Systemic inhibition of NF-κB by the 8K-NBD peptide in Ercc1-/Δ mice increased disc proteoglycan synthesis and ameriolated loss disc cellularity and matrix proteoglycan. These results were confirmed genetically by using the p65 haploinsufficient Ercc1-/Δp65+/- mice. Conclusion These findings demonstrate that the IKK/NF-κB signaling pathway

  11. Methodology for the Incorporation of Passive Component Aging Modeling into the RAVEN/ RELAP-7 Environment

    SciTech Connect

    Mandelli, Diego; Rabiti, Cristian; Cogliati, Joshua; Alfonsi, Andrea; Askin Guler; Tunc Aldemir

    2014-11-01

    Passive system, structure and components (SSCs) will degrade over their operation life and this degradation may cause to reduction in the safety margins of a nuclear power plant. In traditional probabilistic risk assessment (PRA) using the event-tree/fault-tree methodology, passive SSC failure rates are generally based on generic plant failure data and the true state of a specific plant is not reflected realistically. To address aging effects of passive SSCs in the traditional PRA methodology [1] does consider physics based models that account for the operating conditions in the plant, however, [1] does not include effects of surveillance/inspection. This paper represents an overall methodology for the incorporation of aging modeling of passive components into the RAVEN/RELAP-7 environment which provides a framework for performing dynamic PRA. Dynamic PRA allows consideration of both epistemic and aleatory uncertainties (including those associated with maintenance activities) in a consistent phenomenological and probabilistic framework and is often needed when there is complex process/hardware/software/firmware/ human interaction [2]. Dynamic PRA has gained attention recently due to difficulties in the traditional PRA modeling of aging effects of passive components using physics based models and also in the modeling of digital instrumentation and control systems. RAVEN (Reactor Analysis and Virtual control Environment) [3] is a software package under development at the Idaho National Laboratory (INL) as an online control logic driver and post-processing tool. It is coupled to the plant transient code RELAP-7 (Reactor Excursion and Leak Analysis Program) also currently under development at INL [3], as well as RELAP 5 [4]. The overall methodology aims to: • Address multiple aging mechanisms involving large number of components in a computational feasible manner where sequencing of events is conditioned on the physical conditions predicted in a simulation

  12. Joint Modelling of Survival and Emergency Medical Care Usage in Spanish Insureds Aged 65+

    PubMed Central

    2016-01-01

    Background We study the longevity and medical resource usage of a large sample of insureds aged 65 years or older drawn from a large health insurance dataset. Yearly counts of each subject's emergency room and ambulance service use and hospital admissions are made. Occurrence of mortality is also monitored. The study aims to capture the simultaneous dependence between their demand for healthcare and survival. Methods We demonstrate the benefits of taking a joint approach to modelling longitudinal and survival processes by using a large dataset from a Spanish medical mutual company. This contains historical insurance information for 39,137 policyholders aged 65+ (39.5% men and 60.5% women) across the eight-year window of the study. The joint model proposed incorporates information on longitudinal demand for care in a weighted cumulative effect that places greater emphasis on more recent than on past service demand. Results A strong significant and positive relationship between the exponentially weighted demand for emergency, ambulance and hospital services is found with risk of death (alpha = 1.462, p < 0.001). Alternative weighting specifications are tested, but in all cases they show that a joint approach indicates a close connection between health care demand and time-to-death. Additionally, the model allows us to predict individual survival curves dynamically as new information on demand for services becomes known. Conclusions The joint model fitted demonstrates the utility of analysing demand for medical services and survival simultaneously. Likewise, it allows the personalized prediction of survival in advanced age subjects. PMID:27073868

  13. Age models for peat deposits on the basis of coupled lead-210 and radiocarbon data.

    NASA Astrophysics Data System (ADS)

    Piotrowska, Natalia; de Vleeschouwer, François; Sikorski, Jarosław; Sensuła, Barbara; Michczyński, Adam; Fiałkiewicz-Kozieł, Barbara; Palowski, Bernard

    2010-05-01

    The study presents three examples of age-model construction based on the results of 210Pb and 14C dating methods applied to peat deposits. The three sites are ombrotrophic peat bogs: the Misten (Belgium), Slowinskie Bloto (N Poland) and Puscizna Mala (S Poland). All sites have been subjected to multiproxy studies aimed at reconstructing paleoenvironment and human activity, covering the last 1500, 1300 and 1800 years, respectively (De Vleeschouwer et al. 2009A, 2009B, in prep., Fialkiewicz-Koziel, ongoing PhD). A detailed comparison between 210Pb and post-bomb 14C results in the Misten bog has also been carried out by Piotrowska et al. (2009). In all cores, the 210Pb activity was calculated using 210Po and 208Po activities after acid-extraction from bulk samples, subsequent deposition on silver discs and measurements by alpha spectrometry. Unsupported 210Pb was detected until 35cm in Slowinskie Bloto, 15cm in the Misten and 19cm in Puscizna Mala. Constant Rate of Supply (CRS) model was then applied to compute ages of each 1-cm core interval. For the Misten and Slowinskie Bloto, radiocarbon measurements were performed on selected aboveground plant macrofossils, mainly Sphagnum spp. or Calluna vulgaris, Erica tetralix, and Andromeda polyfolia. Radiocarbon ages were determined using accelerator mass spectrometry (AMS) after acid-alkali-acid wash, combustion, purification of carbon dioxide and graphitisation. For Puscizna Mala bulk samples were dated after chemical preparation of benzene for liquid scintillation counting (LSC) or CO2 for gas proportional counting (GPC). Radiocarbon calibration was undertaken using the Intcal04 calibration curve and OxCal 4 software. As a priori information the 210Pb-derived ages were used in a P_Sequence model (Bronk Ramsey, 2008). A number of dates characterized by low agreement with stratigraphical order had to be considered as outliers and rejected from the final age model. For building a continuous age models a non-linear approach

  14. Threshold behaviour of a SIR epidemic model with age structure and immigration.

    PubMed

    Franceschetti, Andrea; Pugliese, Andrea

    2008-07-01

    We consider a SIR age-structured model with immigration of infectives in all epidemiological compartments; the population is assumed to be in demographic equilibrium between below-replacement fertility and immigration; the spread of the infection occurs through a general age-dependent kernel. We analyse the equations for steady states; because of immigration of infectives a steady state with a positive density of infectives always exists; however, a quasi-threshold theorem is proved, in the sense that, below the threshold, the density of infectives is close to 0, while it is away from 0, above the threshold; furthermore, conditions that guarantee uniqueness of steady states are obtained. Finally, we present some numerical examples, inspired by the Italian demographic situation, that illustrate the threshold-like behaviour, and other features of the stationary solutions and of the transient. PMID:17985131

  15. Modelling the Effects of Ageing Time of Starch on the Enzymatic Activity of Three Amylolytic Enzymes

    PubMed Central

    Guerra, Nelson P.; Pastrana Castro, Lorenzo

    2012-01-01

    The effect of increasing ageing time (t) of starch on the activity of three amylolytic enzymes (Termamyl, San Super, and BAN) was investigated. Although all the enzymatic reactions follow michaelian kinetics, vmax decreased significantly (P < 0.05) and KM increased (although not always significantly) with the increase in t. The conformational changes produced in the starch chains as a consequence of the ageing seemed to affect negatively the diffusivity of the starch to the active site of the enzymes and the release of the reaction products to the medium. A similar effect was observed when the enzymatic reactions were carried out with unaged starches supplemented with different concentrations of gelatine [G]. The inhibition in the amylolytic activities was best mathematically described by using three modified forms of the Michaelis-Menten model, which included a term to consider, respectively, the linear, exponential, and hyperbolic inhibitory effects of t and [G]. PMID:22666116

  16. A diffusion model analysis of the effects of aging on brightness discrimination

    PubMed Central

    RATCLIFF, ROGER; THAPAR, ANJALI; MCKOON, GAIL

    2005-01-01

    The effects of aging on decision time were examined in a brightness discrimination experiment with young and older subjects (ages, 60–75 years). Results showed that older subjects were slightly slower than young subjects but just as accurate. Ratcliff’s (1978) diffusion model was fit to the data, and it provided a good account of response times, their distributions, and response accuracy. There was a 50-msec slowing of the nondecision components of response time for older subjects relative to young subjects, but response criteria settings and rates of accumulation of evidence from stimuli were roughly equal for the two groups. These results are contrasted with those obtained from letter discrimination and signal-detection-like tasks. PMID:12812276

  17. Thermal analysis of pentaerythritol tetranitrate and development of a powder aging model

    SciTech Connect

    Brown, Geoffrey W; Sandstrom, Mary M; Giambra, Anna M; Archuleta, Jose G; Monroe, Deirde C

    2009-01-01

    We have applied a range of different physical and thermal analysis techniques to characterize the thermal evolution of the specific surface area of pentaerythritol tetranitrate (PETN) powders. Using atomic force microscopy we have determined that the mass transfer mechanism leading to powder coarsening is probably sublimation and redeposition of PETN. Using thermogravimetric analysis we have measured vapor pressures of PETN powders whose aging will be simulated in future work. For one specific powder we have constructed an empirical model of the coarsening that is fit to specific surface area measurements at 60 C to 70 C to provide predictive capability of that powder's aging. Modulated differential scanning calorimetry and mass spectroscopy measurements highlight some of the thermal behavior of the powders and suggest that homologue-based eutectics and impurities are localized in the powder particles.

  18. A Combination Cocktail Improves Spatial Attention in a Canine Model of Human Aging and Alzheimer's disease

    PubMed Central

    Head, Elizabeth; Murphey, Heather L.; Dowling, Amy L.S.; McCarty, Katie L.; Bethel, Samuel R.; Nitz, Jonathan A.; Pleiss, Melanie; Vanrooyen, Jenna; Grossheim, Mike; Smiley, Jeffery R.; Murphy, M. Paul; Beckett, Tina L.; Pagani, Dieter; Bresch, Frederick; Hendrix, Curt

    2014-01-01

    Alzheimer's disease (AD) involves multiple pathological processes in the brain, including increased inflammation and oxidative damage, as well as the accumulation of beta-amyloid (Aβ) plaques. We hypothesized that a combinatorial therapeutic approach to target these multiple pathways may provide cognitive and neuropathological benefits for AD patients. To test this hypothesis, we used a canine model of human aging and AD. Aged dogs naturally develop learning and memory impairments, human-type Aβ deposits and oxidative damage in the brain. Thus, 9 aged beagles (98-115 months) were treated with a medical food cocktail containing (1) an extract of turmeric containing 95% curcuminoids; (2) an extract of green tea containing 50% epigallocatechingallate; (3) N-acetyl cysteine; (4) R-alpha lipoic acid; and (5) an extract of black pepper containing 95% piperine. Nine similarly aged dogs served as placebo-treated controls. After 3 months of treatment, 13 dogs completed a variable distance landmark task used as a measure of spatial attention. As compared to placebo-treated animals, dogs receiving the medical food cocktail had significantly lower error scores (t(11)=4.3, p=0.001) and were more accurate across all distances (F(1,9)=20.7, p=0.001), suggesting an overall improvement in spatial attention. Measures of visual discrimination learning, executive function and spatial memory, and levels of brain and CSF Aβ were unaffected by the cocktail. Our results indicate that this medical food cocktail may be beneficial for improving spatial attention and motivation deficits associated with impaired cognition in aging and AD. PMID:22886019

  19. Large impact crater histories of Mars: The effect of different model crater age techniques

    NASA Astrophysics Data System (ADS)

    Robbins, Stuart J.; Hynek, Brian M.; Lillis, Robert J.; Bottke, William F.

    2013-07-01

    Impact events that produce large craters primarily occurred early in the Solar System's history because the largest bolides were remnants from planetary formation. Determining when large impacts occurred on a planetary surface such as Mars can yield clues to the flux of material in the early inner Solar System which, in turn, can constrain other planetary processes such as the timing and magnitude of resurfacing and the history of the martian core dynamo. We have used a large, global planetary database in conjunction with geomorphologic mapping to identify craters superposed on the rims of 78 larger craters with diameters D ⩾ 150 km on Mars, ≈78% of which have not been previously dated in this manner. The densities of superposed craters with diameters larger than 10, 16, 25, and 50 km, as well as isochron fits were used to derive model crater ages of these larger craters and basins from which we derived an impact flux. In discussing these ages, we point out several internal inconsistencies of crater-age modeling techniques and chronology systems and, all told, we explain why we think isochron-fitting is the most reliable indicator of an age. Our results point to a mostly obliterated crater record prior to ˜4.0 Ga with the oldest preserved mappable craters on Mars dating to ˜4.3-4.35 Ga. We have used our results to constrain the cessation time of the martian core dynamo which we found to have occurred between the formation of Ladon and Prometheus basins, approximately 4.06-4.09 Ga. We also show that, overall, surfaces on Mars older than ˜4.0-4.1 Ga have experienced >1 km of resurfacing, while those younger than ˜3.8-3.9 Ga have experienced significantly less.

  20. Toward an animal model of extinction-induced despair: focus on aging and physiological indices.

    PubMed

    Huston, Joseph P; Schulz, Daniela; Topic, Bianca

    2009-08-01

    Behaviors that are under the control of positive or negative reinforcers undergo extinction when the anticipated reward/reinforcer is withheld. Despair, an important symptom of environmentally determined depression in humans, can be generated by extinction, or the failure of expected reward to accrue. Although well known to clinicians dealing with depressive patients, an animal model has not been available for extinction-induced depression. We have made a beginning towards validating such a model, based on the extinction of negatively reinforced behavior in the rat, i.e., upon removal of the possibility to escape onto a safety platform in the water maze. As a marker for despair, we employed behavioral immobility, i.e., the cessation of swimming in the attempt to find safety from the water, presumably, a type of learned helplessness. This measure was sensitive to antidepressants and correlated with neurotransmitter contents, neurotrophins and hypothalamus-pituitary adrenal axis markers in selected sites of the brain. Given that some cases of depression in the elderly may be biologically distinct from others and from early-onset depression, and since particularly the aged are prone to experience extinction-induced despair, we compared aged (ca. 24 months old) animals with adults in most of our studies. We found a number of distinct differences in behavioral and biological measures, indicative of differences in propensity to, as well as response to, extinction-induced despair between aged and adults. Our results add to the body of evidence for differences in the neurobiological substrates of depressive disorders between aged and adults, with the implication for the requirement of different treatment strategies in these two populations. PMID:19350220

  1. An age-dependent model to analyse the evolutionary stability of bacterial quorum sensing.

    PubMed

    Mund, A; Kuttler, C; Pérez-Velázquez, J; Hense, B A

    2016-09-21

    Bacterial communication is enabled through the collective release and sensing of signalling molecules in a process called quorum sensing. Cooperative processes can easily be destabilized by the appearance of cheaters, who contribute little or nothing at all to the production of common goods. This especially applies for planktonic cultures. In this study, we analyse the dynamics of bacterial quorum sensing and its evolutionary stability under two levels of cooperation, namely signal and enzyme production. The model accounts for mutation rates and switches between planktonic and biofilm state of growth. We present a mathematical approach to model these dynamics using age-dependent colony models. We explore the conditions under which cooperation is stable and find that spatial structuring can lead to long-term scenarios such as coexistence or bistability, depending on the non-linear combination of different parameters like death rates and production costs. PMID:26796220

  2. Age Differences in the Demand–Control Model of Work Stress

    PubMed Central

    Shultz, Kenneth S.; Wang, Mo; Crimmins, Eileen M.; Fisher, Gwenith G.

    2010-01-01

    There have been many tests of Karasek’s demand–control model of work stress. However, no studies have examined how the model may differentially apply to older versus younger workers. Due to age changes in cognitive processing, the psychological demands of jobs may interact differently with controls for younger versus older workers. Therefore, the study uses data from the Eurobarometer to examine how the demand–control model of work stress may function differently for older versus younger workers. The results indicate that different controls may in fact buffer different types of job demands for younger versus older workers. The findings reveal that only the interaction between problem solving and time to complete tasks was significant for younger workers. For older workers, however, the interactions between time deadlines and having sufficient time to complete tasks, autonomy, and the interaction between problem solving and schedule flexibility are significant predictors of self-reported stress. PMID:20948986

  3. White spotting variant (Wv) mouse as an experimental model for ovarian aging and menopausal biology

    PubMed Central

    Smith, Elizabeth R.; Yeasky, Toni; Wei, Jain Qin; Miki, Roberto A.; Cai, Kathy Q.; Smedberg, Jennifer L.; Yang, Wan-Lin; Xu, Xiang-Xi

    2011-01-01

    Objective Menopause is a unique phenomenon in modern women, as most mammalian species possess a reproductive period comparable to their lifespan. Menopause is caused by the depletion of germ cell-containing ovarian follicles, and in laboratory studies is usually modeled in animals in which the ovarian function is removed by ovariectomy or chemical poisoning of the germ cells. Our objective was to explore and characterize the white spotting variant (Wv) mice that have reduced ovarian germ cell abundance, a result of a point mutation in the c-kit gene that decreases the kinase activity, as a genetic model for use in menopausal studies. Methods Physiological and morphological features associated with menopause were determined in female Wv/Wv mice compared to age-matched wildtype controls. Immunohistochemistry was used to evaluate the presence and number of follicles in paraffin-embedded ovaries. Bone density and body composition were evaluated using the PIXImus X-ray densitometer, and lipids, calcium, and hormone levels were determined in serum using antigen-specific EIAs. Heart and body weight were measured, and cardiac function was evaluated by transthoracic echocardiography. Results The ovaries of the Wv/Wv females have a greatly reduced number of normal germ cells at birth compared to wildtype mice. The remaining follicles are depleted by around 2 months, and the ovaries develop benign epithelial lesions that resemble morphological changes that occur during ovarian aging, whereas a normal mouse ovary has numerous follicles at all stages of development and retains some follicles even in advanced age. Wv mice have elevated plasma gonadotrophins and reduced estrogen and progesterone levels, a significant reduction in bone mass density, and elevated serum cholesterol and lipoprotein levels. Moreover, the Wv female mice have enlarged hearts and reduced cardiac function. Conclusions The reduction of c-kit activity in Wv mice leads to a substantially diminished

  4. Future challenges for clinical care of an ageing population infected with HIV: a modelling study

    PubMed Central

    Smit, Mikaela; Brinkman, Kees; Geerlings, Suzanne; Smit, Colette; Thyagarajan, Kalyani; Sighem, Ard van; de Wolf, Frank; Hallett, Timothy B

    2015-01-01

    Summary Background The population infected with HIV is getting older and these people will increasingly develop age-related non-communicable diseases (NCDs). We aimed to quantify the scale of the change and the implications for HIV care in the Netherlands in the future. Methods We constructed an individual-based model of the ageing HIV-infected population, which followed patients on HIV treatment as they age, develop NCDs—including cardiovascular disease (hypertension, hypercholesterolaemia, myocardial infarctions, and strokes), diabetes, chronic kidney disease, osteoporosis, and non-AIDS malignancies—and start co-medication for these diseases. The model was parameterised by use of data for 10 278 patients from the national Dutch ATHENA cohort between 1996 and 2010. We made projections up to 2030. Findings Our model suggests that the median age of HIV-infected patients on combination antiretroviral therapy (ART) will increase from 43·9 years in 2010 to 56·6 in 2030, with the proportion of HIV-infected patients aged 50 years or older increasing from 28% in 2010 to 73% in 2030. In 2030, we predict that 84% of HIV-infected patients will have at least one NCD, up from 29% in 2010, with 28% of HIV-infected patients in 2030 having three or more NCDs. 54% of HIV-infected patients will be prescribed co-medications in 2030, compared with 13% in 2010, with 20% taking three or more co-medications. Most of this change will be driven by increasing prevalence of cardiovascular disease and associated drugs. Because of contraindications and drug–drug interactions, in 2030, 40% of patients could have complications with the currently recommended first-line HIV regimens. Interpretation The profile of patients in the Netherlands infected with HIV is changing, with increasing numbers of older patients with multiple morbidities. These changes mean that, in the near future, HIV care will increasingly need to draw on a wide range of medical disciplines, in addition to evidence

  5. Anti-aging Effect of Transplanted Amniotic Membrane Mesenchymal Stem Cells in a Premature Aging Model of Bmi-1 Deficiency

    PubMed Central

    Xie, Chunfeng; Jin, Jianliang; Lv, Xianhui; Tao, Jianguo; Wang, Rong; Miao, Dengshun

    2015-01-01

    To determine whether transplanted amniotic membrane mesenchymal stem cells (AMSCs) ameliorated the premature senescent phenotype of Bmi-1-deficient mice, postnatal 2-day-old Bmi-1−/− mice were injected intraperitoneally with the second-passage AMSCs from amniotic membranes of β-galactosidase (β-gal) transgenic mice or wild-type (WT) mice labeled with DiI. Three reinjections were given, once every seven days. Phenotypes of 5-week-old β-gal+ AMSC-transplanted or 6-week-old DiI+ AMSC-transplanted Bmi-1−/− mice were compared with vehicle-transplanted Bmi-1−/− and WT mice. Vehicle-transplanted Bmi-1−/− mice displayed growth retardation and premature aging with decreased cell proliferation and increased cell apoptosis; a decreased ratio and dysmaturity of lymphocytic series; premature osteoporosis with reduced osteogenesis and increased adipogenesis; redox imbalance and DNA damage in multiple organs. Transplanted AMSCs carried Bmi-1 migrated into multiple organs, proliferated and differentiated into multiple tissue cells, promoted growth and delayed senescence in Bmi-1−/− transplant recipients. The dysmaturity of lymphocytic series were ameliorated, premature osteoporosis were rescued by promoting osteogenesis and inhibiting adipogenesis, the oxidative stress and DNA damage in multiple organs were inhibited by the AMSC transplantation in Bmi-1−/− mice. These findings indicate that AMSC transplantation ameliorated the premature senescent phenotype of Bmi-1-deficient mice and could be a novel therapy to delay aging and prevent aging-associated degenerative diseases. PMID:26370922

  6. Vitamin C alleviates aging defects in a stem cell model for Werner syndrome.

    PubMed

    Li, Ying; Zhang, Weizhou; Chang, Liang; Han, Yan; Sun, Liang; Gong, Xiaojun; Tang, Hong; Liu, Zunpeng; Deng, Huichao; Ye, Yanxia; Wang, Yu; Li, Jian; Qiao, Jie; Qu, Jing; Zhang, Weiqi; Liu, Guang-Hui

    2016-07-01

    Werner syndrome (WS) is a premature aging disorder that mainly affects tissues derived from mesoderm. We have recently developed a novel human WS model using WRN-deficient human mesenchymal stem cells (MSCs). This model recapitulates many phenotypic features of WS. Based on a screen of a number of chemicals, here we found that Vitamin C exerts most efficient rescue for many features in premature aging as shown in WRN-deficient MSCs, including cell growth arrest, increased reactive oxygen species levels, telomere attrition, excessive secretion of inflammatory factors, as well as disorganization of nuclear lamina and heterochromatin. Moreover, Vitamin C restores in vivo viability of MSCs in a mouse model. RNA sequencing analysis indicates that Vitamin C alters the expression of a series of genes involved in chromatin condensation, cell cycle regulation, DNA replication, and DNA damage repair pathways in WRN-deficient MSCs. Our results identify Vitamin C as a rejuvenating factor for WS MSCs, which holds the potential of being applied as a novel type of treatment of WS. PMID:27271327

  7. Self-oscillating Vocal Fold Model Mechanics: Healthy, Diseased, and Aging

    NASA Astrophysics Data System (ADS)

    Hiubler, Elizabeth P.; Pollok, Lucas F. E.; Apostoli, Adam G.; Hancock, Adrienne B.; Plesniak, Michael W.

    2014-11-01

    Voice disorders have been estimated to have a substantial economic impact of 2.5 billion annually. Approximately 30% of people will suffer from a voice disorder at some point in their lives. Life-sized, self-oscillating, synthetic vocal fold (VF) models are fabricated to exhibit material properties representative of human VFs. These models are created both with and without a polyp-like structure, a pathology that has been shown to produce rich viscous flow structures not normally observed for healthy VFs during normal phonation. Pressure measurements are acquired upstream of the VFs and high-speed images are captured at varying flow rates during VF oscillation to facilitate an understanding of the characteristics of healthy and diseased VFs. The images are analyzed using a videokymography line-scan technique. Clinically-relevant parameters calculated from the volume-velocity output of a circumferentially-vented mask (Rothenberg mask) are compared to human data collected from two groups of males aged 18-30 and 60-80. This study extends the use of synthetic VF models by assessing their ability to replicate behaviors observed in human subject data to advance a means of investigating changes associated with normal, pathological, and the aging voice. Supported by the GWU Institute for Biomedical Engineering (GWIBE) and GWU Center for Biomimetics and Bioinspired Engineering (COBRE).

  8. Diagenetic modification of Sm-Nd model ages in Tertiary sandstones and shales, Texas Gulf Coast

    SciTech Connect

    Awwiller, D.N.; Mack, L.E. )

    1991-04-01

    Sm-Nd model ages of sandstones and shales from the Oligocene Frio Formation of south Texas and the Paleocene-Eocene Wilcox Group of south-central Texas increase with increasing depth of burial. The sampling scheme employed minimizes, but does not eliminate, the possibility that these trends in depleted-mantle model ages (T{sub dm}) are due to detrital variability. Close correlation of these trends with diagenetic changes in the rock and evidence of rare earth element mobility preserved in the diagenetic products suggests that diagenesis has modified T{sub dm}. Diagenetic modification of T{sub dm} in Frio sandstone and Wilcox shale is due primarily to loss of radiogenic Nd, whereas increased {sup 147}Sm/{sup 144}Nd (Sm/Nd) produces elevated T{sub dm} in deeper Wilcox sandstones. The T{sub dm} of Frio shales does not change appreciably with depth, owing to the opposite effects on T{sub dm} of decreased Sm/Nd and decreased {epsilon}{sub Nd}(0). Loss of radiogenic Nd is due primarily to reactions involving unstable volcanic detritus, which is more abundant in Frio than in the Wilcox. Decreased Sm/Nd in authigenic illite, and consequent increased Sm/Nd in pore fluids, results in elevated T{sub dm} in Wilcox and Frio sandstones containing late-diagenetic cement, and in decreased Sm/Nd in deeper Frio shale. The similar T{sub dm} trends observed in both units, which have different detrital characteristics, suggest that modification of Sm-Nd model ages in siliciclastic rocks may be commonplace during burial diagensis.

  9. Modeling of Late Blooming Phases and Precipitation Kinetics in Aging Reactor Pressure Vessel (RPV) Steels

    SciTech Connect

    Yongfeng Zhang; Pritam Chakraborty; S. Bulent Biner

    2013-09-01

    The principle work at the atomic scale is to develop a predictive quantitative model for the microstructure evolution of RPV steels under thermal aging and neutron radiation. We have developed an AKMC method for the precipitation kinetics in bcc-Fe, with Cu, Ni, Mn and Si being the alloying elements. In addition, we used MD simulations to provide input parameters (if not available in literature). MMC simulations were also carried out to explore the possible segregation/precipitation morphologies at the lattice defects. First we briefly describe each of the simulation algorithms, then will present our results.

  10. Testing Models of Psychopathology in Preschool-aged Children Using a Structured Interview-based Assessment

    PubMed Central

    Dougherty, Lea R.; Bufferd, Sara J.; Carlson, Gabrielle A.; Klein, Daniel N.

    2014-01-01

    A number of studies have found that broadband internalizing and externalizing factors provide a parsimonious framework for understanding the structure of psychopathology across childhood, adolescence, and adulthood. However, few of these studies have examined psychopathology in young children, and several recent studies have found support for alternative models, including a bi-factor model with common and specific factors. The present study used parents’ (typically mothers’) reports on a diagnostic interview in a community sample of 3-year old children (n=541; 53.9 % male) to compare the internalizing-externalizing latent factor model with a bi-factor model. The bi-factor model provided a better fit to the data. To test the concurrent validity of this solution, we examined associations between this model and paternal reports and laboratory observations of child temperament. The internalizing factor was associated with low levels of surgency and high levels of fear; the externalizing factor was associated with high levels of surgency and disinhibition and low levels of effortful control; and the common factor was associated with high levels of surgency and negative affect and low levels of effortful control. These results suggest that psychopathology in preschool-aged children may be explained by a single, common factor influencing nearly all disorders and unique internalizing and externalizing factors. These findings indicate that shared variance across internalizing and externalizing domains is substantial and are consistent with recent suggestions that emotion regulation difficulties may be a common vulnerability for a wide array of psychopathology. PMID:24652485

  11. Aging and orthopedics: how a lifespan development model can inform practice and research

    PubMed Central

    Gautreau, Sylvia; Gould, Odette N.; Forsythe, Michael E.

    2016-01-01

    Orthopedic surgical care, like all health care today, is in flux owing to an aging population and to chronic medical conditions leading to an increased number of people with illnesses that need to be managed over the lifespan. The result is an ongoing shift from curing acute illnesses to the management and care of chronic illness and conditions. Theoretical models that provide a useful and feasible vision for the future of health care and health care research are needed. This review discusses how the lifespan development model used in some disciplines within the behavioural sciences can be seen as an extension of the biopsychosocial model. We posit that the lifespan development model provides useful perspectives for both orthopedic care and research. We present key concepts and recommendations, and we discuss how the lifespan development model can contribute to new and evolving perspectives on orthopedic outcomes and to new directions for research. We also offer practical guidelines on how to implement the model in orthopedic practice. PMID:27240129

  12. A computational model associating learning process, word attributes, and age of acquisition.

    PubMed

    Hidaka, Shohei

    2013-01-01

    We propose a new model-based approach linking word learning to the age of acquisition (AoA) of words; a new computational tool for understanding the relationships among word learning processes, psychological attributes, and word AoAs as measures of vocabulary growth. The computational model developed describes the distinct statistical relationships between three theoretical factors underpinning word learning and AoA distributions. Simply put, this model formulates how different learning processes, characterized by change in learning rate over time and/or by the number of exposures required to acquire a word, likely result in different AoA distributions depending on word type. We tested the model in three respects. The first analysis showed that the proposed model accounts for empirical AoA distributions better than a standard alternative. The second analysis demonstrated that the estimated learning parameters well predicted the psychological attributes, such as frequency and imageability, of words. The third analysis illustrated that the developmental trend predicted by our estimated learning parameters was consistent with relevant findings in the developmental literature on word learning in children. We further discuss the theoretical implications of our model-based approach. PMID:24223699

  13. Aging and orthopedics: how a lifespan development model can inform practice and research.

    PubMed

    Gautreau, Sylvia; Gould, Odette N; Forsythe, Michael E

    2016-08-01

    Orthopedic surgical care, like all health care today, is in flux owing to an aging population and to chronic medical conditions leading to an increased number of people with illnesses that need to be managed over the lifespan. The result is an ongoing shift from curing acute illnesses to the management and care of chronic illness and conditions. Theoretical models that provide a useful and feasible vision for the future of health care and health care research are needed. This review discusses how the lifespan development model used in some disciplines within the behavioural sciences can be seen as an extension of the biopsychosocial model. We posit that the lifespan development model provides useful perspectives for both orthopedic care and research. We present key concepts and recommendations, and we discuss how the lifespan development model can contribute to new and evolving perspectives on orthopedic outcomes and to new directions for research. We also offer practical guidelines on how to implement the model in orthopedic practice. PMID:27240129

  14. A physics based reduced order aging model for lithium-ion cells with phase change

    NASA Astrophysics Data System (ADS)

    Gambhire, Priya; Hariharan, Krishnan S.; Khandelwal, Ashish; Kolake, Subramanya Mayya; Yeo, Taejung; Doo, Seokgwang

    2014-12-01

    The electrochemical model has the potential to provide a robust and accurate battery management system, but is not the preferred choice as it involves solving non-linear, coupled partial differential equations. In the present work, a model order reduction of the complete electrochemical model for a lithium ion cell with phase change electrodes is carried out. The phase change phenomenon is described using a simple, concentration-dependent diffusivity derived from mixture rules. This reduced order model (ROM) is validated with experimental data from literature. The applicability of the model to capture the atypical behavior of the phase change electrode system is demonstrated. Using the cell response from ROM, charge-discharge asymmetry and path dependence in a lithium iron phosphate (LFP) cell are explored in detail. In addition, side reaction kinetics and solid electrolyte interphase formation are included in the ROM framework to enhance its capability to predict cell aging. The model is used to investigate capacity losses occurring in a phase change electrode cell. Insights from these results are used to suggest cell operating guidelines for maximizing utilization.

  15. Comprehensive Equivalent Circuit Based Modeling and Model Based Management of Aged Lithium ion Batteries

    NASA Astrophysics Data System (ADS)

    Tong, Shijie

    Energy storage is one of society's grand challenges for the 21st century. Lithium ion batteries (LIBs) are widely used in mobile devices, transportation, and stationary energy storages due to lowering cost combined with excellent power/energy density as well as cycle durability. The need for a battery management system (BMS) arises from a demand to improve cycle life, assure safety, and optimize the full pack performance. In this work, we proposed a model based battery on-line state of charge (SoC) and state of health (SoH) estimator for LIBs. The estimator incorporates a comprehensive Equivalent Circuit Model (ECM) as reference, an Extended Kalman Filter (EKF) as state observer, a Recursive Least Square (RLS) algorithm as parameter identifier, and Parameter Varying Approach (PVA) based optimization algorithms for the parameter function regressions. The developed adaptive estimator was applied to a 10kW smart grid energy storage application using retired electric vehicle batteries. The estimator exhibits a high numerical efficiency as well as an excellent accuracy in estimating SoC and SoH. The estimator also provides a novel method to optimize the correlation between battery open circuit voltage (OCV) and SoC, which further improves states estimation accuracy.

  16. An age-specific kinetic model of lead metabolism in humans.

    PubMed Central

    Leggett, R W

    1993-01-01

    Although considerable progress has been made in recent years in reducing human exposures to lead, the potential for high intake of this contaminant still exists in millions of homes and in many occupational settings. Moreover, there is growing evidence that levels of lead intake considered inconsequential just a few years ago can result in subtle, adverse health effects, particularly in children. Consequently, there have been increased efforts by health protection agencies to develop credible, versatile methods for relating levels of lead in environmental media to levels in blood and tissues of exposed humans of all ages. In a parallel effort motivated largely by the Chernobyl nuclear accident, the International Commission on Radiological Protection (ICRP) is assembling a set of age-specific biokinetic models for calculating radiation doses from environmentally important radionuclides, including radioisotopes of lead. This paper describes a new age-specific biokinetic model for lead originally developed for the ICRP but expanded to include additional features that are useful for consideration of lead as a chemical toxin. The model is developed within a generic, physiologically motivated framework designed to address a class of calciumlike elements. This framework provides a useful setting in which to synthesize experimental, occupational, and environmental data on lead and exploit common physiological properties of lead and the alkaline earth elements. The modular design is intended to allow researchers to modify specific parameter values or model components to address special problems in lead toxicology or to incorporate new information. Transport of lead between compartments is assumed to follow linear, first-order kinetics provided the concentration in red blood cells remains below a nonlinear threshold level, but a nonlinear relation between plasma lead and red blood cell lead is modeled for concentrations above that level. The model is shown to be consistent

  17. Inflammation and Cell Death in Age-Related Macular Degeneration: An Immunopathological and Ultrastructural Model.

    PubMed

    Ardeljan, Christopher P; Ardeljan, Daniel; Abu-Asab, Mones; Chan, Chi-Chao

    2014-01-01

    The etiology of Age-related Macular Degeneration (AMD) remains elusive despite the characterization of many factors contributing to the disease in its late-stage phenotypes. AMD features an immune system in flux, as shown by changes in macrophage polarization with age, expression of cytokines and complement, microglial accumulation with age, etc. These point to an allostatic overload, possibly due to a breakdown in self vs. non-self when endogenous compounds and structures acquire the appearance of non-self over time. The result is inflammation and inflammation-mediated cell death. While it is clear that these processes ultimately result in degeneration of retinal pigment epithelium and photoreceptor, the prevalent type of cell death contributing to the various phenotypes is unknown. Both molecular studies as well as ultrastructural pathology suggest pyroptosis, and perhaps necroptosis, are the predominant mechanisms of cell death at play, with only minimal evidence for apoptosis. Herein, we attempt to reconcile those factors identified by experimental AMD models and integrate these data with pathology observed under the electron microscope-particularly observations of mitochondrial dysfunction, DNA leakage, autophagy, and cell death. PMID:25580276

  18. C. elegans model identifies genetic modifiers of alpha-synuclein inclusion formation during aging.

    PubMed

    van Ham, Tjakko J; Thijssen, Karen L; Breitling, Rainer; Hofstra, Robert M W; Plasterk, Ronald H A; Nollen, Ellen A A

    2008-03-01

    Inclusions in the brain containing alpha-synuclein are the pathological hallmark of Parkinson's disease, but how these inclusions are formed and how this links to disease is poorly understood. We have developed a C. elegans model that makes it possible to monitor, in living animals, the formation of alpha-synuclein inclusions. In worms of old age, inclusions contain aggregated alpha- synuclein, resembling a critical pathological feature. We used genome-wide RNA interference to identify processes involved in inclusion formation, and identified 80 genes that, when knocked down, resulted in a premature increase in the number of inclusions. Quality control and vesicle-trafficking genes expressed in the ER/Golgi complex and vesicular compartments were overrepresented, indicating a specific role for these processes in alpha-synuclein inclusion formation. Suppressors include aging-associated genes, such as sir-2.1/SIRT1 and lagr-1/LASS2. Altogether, our data suggest a link between alpha-synuclein inclusion formation and cellular aging, likely through an endomembrane-related mechanism. The processes and genes identified here present a framework for further study of the disease mechanism and provide candidate susceptibility genes and drug targets for Parkinson's disease and other alpha-synuclein related disorders. PMID:18369446

  19. Thermal characterization and model free kinetics of aged epoxies and foams using TGA and DSC methods.

    SciTech Connect

    Cordaro, Joseph Gabriel; Kruizenga, Alan Michael; Nissen, April

    2013-10-01

    Two classes of materials, poly(methylene diphenyl diisocyanate) or PMDI foam, and cross-linked epoxy resins, were characterized using thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC), to help understand the effects of aging and %E2%80%9Cbake-out%E2%80%9D. The materials were evaluated for mass loss and the onset of decomposition. In some experiments, volatile materials released during heating were analyzed via mass spectroscopy. In all, over twenty materials were evaluated to compare the mass loss and onset temperature for decomposition. Model free kinetic (MFK) measurements, acquired using variable heating rate TGA experiments, were used to calculate the apparent activation energy of thermal decomposition. From these compiled data the effects of aging, bake-out, and sample history on the thermal stability of materials were compared. No significant differences between aged and unaged materials were detected. Bake-out did slightly affect the onset temperature of decomposition but only at the highest bake-out temperatures. Finally, some recommendations for future handling are made.

  20. Modeling tracers of young stellar population age in star-forming galaxies

    SciTech Connect

    Levesque, Emily M.; Leitherer, Claus

    2013-12-20

    The young stellar population of a star-forming galaxy is the primary engine driving its radiative properties. As a result, the age of a galaxy's youngest generation of stars is critical for a detailed understanding of its star formation history, stellar content, and evolutionary state. Here we present predicted equivalent widths for the Hβ, Hα, and Brγ recombination lines as a function of stellar population age. The equivalent widths are produced by the latest generations of stellar evolutionary tracks and the Starburst99 stellar population synthesis code, and are the first to fully account for the combined effects of both nebular emission and continuum absorption produced by the synthetic stellar population. Our grid of model stellar populations spans six metallicities (0.001 < Z < 0.04), two treatments of star formation history (a 10{sup 6} M {sub ☉} instantaneous burst and a continuous star formation rate of 1 M {sub ☉} yr{sup –1}), and two different treatments of initial rotation rate (v {sub rot} = 0.0v {sub crit} and 0.4v {sub crit}). We also investigate the effects of varying the initial mass function. Given constraints on galaxy metallicity, our predicted equivalent widths can be applied to observations of star-forming galaxies to approximate the age of their young stellar populations.

  1. Botryllus schlosseri, an emerging model for the study of aging, stem cells, and mechanisms of regeneration

    PubMed Central

    Voskoboynik, Ayelet; Weissman, Irving L.

    2015-01-01

    The decline of tissue regenerative potential with the loss of stem cell function is a hallmark of mammalian aging. We study Botryllus schlosseri, a colonial chordate which exhibits robust stem cell-mediated regeneration capacities throughout life. Larvae, derived by sexual reproduction and chordate development, metamorphose to clonal founders that undergo weekly formation of new individuals by budding from stem cells. Individuals are transient structures which die through massive apoptosis, and successive buds mature to replicate an entire new body. As a result, their stem cells, which are the only self-renewing cells in a tissue, are the only cells which remain through the entire life of the genotype and retain the effects of time. During aging, a significant decrease in the colonies’ regenerative potential is observed and both sexual and asexual reproductions will eventually halt. When a parent colony is experimentally separated into a number of clonal replicates, they frequently undergo senescence simultaneously, suggesting a heritable factor that determines lifespan in these colonies. The availability of the recently published B. schlosseri genome coupled with its unique life cycle features promotes the use of this model organism for the study of the evolution of aging, stem cells, and mechanisms of regeneration. PMID:26136618

  2. Mediational Role of Age of Onset in Gambling Disorder, a Path Modeling Analysis.

    PubMed

    Jiménez-Murcia, Susana; Granero, Roser; Tárrega, Salomé; Angulo, Ariadna; Fernández-Aranda, Fernando; Arcelus, Jon; Fagundo, Ana B; Aymamí, Neus; Moragas, Laura; Sauvaget, Anne; Grall-Bronnec, Marie; Gómez-Peña, Mónica; Menchón, José M

    2016-03-01

    The aim of the study is to assess a mediational pathway, which includes patients' sex, personality traits, age of onset of gambling disorder (GD) and gambling-related variables. The South Oaks Gambling Screen, the Symptom Checklist (SCL-90-R) and the Temperament and Character Inventory-R were administered to a large sample of 1632 outpatients attending a specialized outpatient GD unit. Sociodemographic variables were also recorded. A Structural Equation Model was adjusted to assess the pathway. Age of onset mediated between personality profile (novelty seeking and self-transcendence) and GD severity and depression symptoms (measured by SCL-90-R). Sex had a direct effect on GD onset and depression symptoms: men initiated the GD earlier and reported fewer depression symptoms. Age of onset is a mediating variable between sex, personality traits, GD severity and depression symptoms. These empirical results provide new evidence about the underlying etiological process of dysfunctional behaviors related to gambling, and may help to guide the development of more effective treatment and prevention programs aimed at high-risk groups such as young men with high levels of novelty seeking and self-transcendence. PMID:25814276

  3. Hind limb unloading, a model of spaceflight conditions, leads to decreased B lymphopoiesis similar to aging.

    PubMed

    Lescale, Chloé; Schenten, Véronique; Djeghloul, Dounia; Bennabi, Meriem; Gaignier, Fanny; Vandamme, Katleen; Strazielle, Catherine; Kuzniak, Isabelle; Petite, Hervé; Dosquet, Christine; Frippiat, Jean-Pol; Goodhardt, Michele

    2015-02-01

    Within the bone marrow, the endosteal niche plays a crucial role in B-cell differentiation. Because spaceflight is associated with osteoporosis, we investigated whether changes in bone microstructure induced by a ground-based model of spaceflight, hind limb unloading (HU), could affect B lymphopoiesis. To this end, we analyzed both bone parameters and the frequency of early hematopoietic precursors and cells of the B lineage after 3, 6, 13, and 21 d of HU. We found that limb disuse leads to a decrease in both bone microstructure and the frequency of B-cell progenitors in the bone marrow. Although multipotent hematopoietic progenitors were not affected by HU, a decrease in B lymphopoiesis was observed as of the common lymphoid progenitor (CLP) stage with a major block at the progenitor B (pro-B) to precursor B (pre-B) cell transition (5- to 10-fold decrease). The modifications in B lymphopoiesis were similar to those observed in aged mice and, as with aging, decreased B-cell generation in HU mice was associated with reduced expression of B-cell transcription factors, early B-cell factor (EBF) and Pax5, and an alteration in STAT5-mediated IL-7 signaling. These findings demonstrate that mechanical unloading of hind limbs results in a decrease in early B-cell differentiation resembling age-related modifications in B lymphopoiesis. PMID:25376832

  4. Losses of dissolved CO2 through the cork stopper during Champagne aging: toward a multiparameter modeling.

    PubMed

    Liger-Belair, Gérard; Villaume, Sandra

    2011-04-27

    Measurements of dissolved CO(2) concentrations from Champagne bottles initially holding the same CO(2) level after having been elaborated (close to 11.5 g L(-1)), but having experienced different periods of aging after having been corked with natural cork stoppers, were done. Losses of dissolved CO(2) close to 3.5 g L(-1) experienced by the oldest Champagne samples aged for about 75 months were reported. This very significant loss of dissolved CO(2) was logically interpreted as a consequence of the continuous diffusion of gaseous CO(2) through the pores of the cork stopper. By combining the diffusion principle through a porous medium with Henry's law (which links the solubility of a gas species in a liquid medium with its partial pressure in the vapor phase), a multiparameter model was built that provides the dissolved CO(2) content found in Champagne during its whole aging period. Both Champagne temperature and bottle volume were found to be key parameters with regard to the kinetics of CO(2) losses through the cork. PMID:21413811

  5. Biological reaction to polyethylene particles in a murine calvarial model is highly influenced by age.

    PubMed

    Langlois, Jean; Zaoui, Amine; Bichara, David A; Nich, Christophe; Bensidhoum, Morad; Petite, Hervé; Muratoglu, Orhun K; Hamadouche, Moussa

    2016-04-01

    Particle-induced osteolysis is driven by multiple factors including bone metabolism, inflammation, and age. The objective of this study was to determine the influence of age on polyethylene (PE) particle-induced osteolysis in a murine calvarial model comparing 2-month-old (young) versus 24-month-old (old) mice. After PE particle implantation, calvaria were assessed at days (D) 3, D7, D14, and D21 via chemoluminescent imaging for inflammation (L-012 probe). In addition micro-computed tomography (micro-CT) and histomorphometry end points addressed the bone reaction. Inflammation peaked at D7 in young mice and D14 in old mice. Using micro-CT, a nadir of mature bone was recorded at D7 for young mice, versus D21 for old mice. Besides, regenerating bone peaked at distinct timepoints: D7 for young mice versus D21 for old mice. In the young mice group, the histomorphometric findings correlated with micro-CT regenerating bone findings at D7, associated with ample osteoïd deposition. No osteoïd could be histologically quantified in the old mice group at D7. This study demonstrated that the biological reaction to polyethylene particles is highly influenced by age. PMID:26375608

  6. Incorporating harvest rates into the sex-age-kill model for white-tailed deer

    USGS Publications Warehouse

    Norton, Andrew S.; Diefenbach, Duane R.; Rosenberry, Christopher S.; Wallingford, Bret D.

    2013-01-01

    Although monitoring population trends is an essential component of game species management, wildlife managers rarely have complete counts of abundance. Often, they rely on population models to monitor population trends. As imperfect representations of real-world populations, models must be rigorously evaluated to be applied appropriately. Previous research has evaluated population models for white-tailed deer (Odocoileus virginianus); however, the precision and reliability of these models when tested against empirical measures of variability and bias largely is untested. We were able to statistically evaluate the Pennsylvania sex-age-kill (PASAK) population model using realistic error measured using data from 1,131 radiocollared white-tailed deer in Pennsylvania from 2002 to 2008. We used these data and harvest data (number killed, age-sex structure, etc.) to estimate precision of abundance estimates, identify the most efficient harvest data collection with respect to precision of parameter estimates, and evaluate PASAK model robustness to violation of assumptions. Median coefficient of variation (CV) estimates by Wildlife Management Unit, 13.2% in the most recent year, were slightly above benchmarks recommended for managing game species populations. Doubling reporting rates by hunters or doubling the number of deer checked by personnel in the field reduced median CVs to recommended levels. The PASAK model was robust to errors in estimates for adult male harvest rates but was sensitive to errors in subadult male harvest rates, especially in populations with lower harvest rates. In particular, an error in subadult (1.5-yr-old) male harvest rates resulted in the opposite error in subadult male, adult female, and juvenile population estimates. Also, evidence of a greater harvest probability for subadult female deer when compared with adult (≥2.5-yr-old) female deer resulted in a 9.5% underestimate of the population using the PASAK model. Because obtaining

  7. Age-structured mark-recapture analysis: A virtual-population-analysis-based model for analyzing age-structured capture-recapture data

    USGS Publications Warehouse

    Coggins, L.G., Jr.; Pine, William E., III; Walters, C.J.; Martell, S.J.D.

    2006-01-01

    We present a new model to estimate capture probabilities, survival, abundance, and recruitment using traditional Jolly-Seber capture-recapture methods within a standard fisheries virtual population analysis framework. This approach compares the numbers of marked and unmarked fish at age captured in each year of sampling with predictions based on estimated vulnerabilities and abundance in a likelihood function. Recruitment to the earliest age at which fish can be tagged is estimated by using a virtual population analysis method to back-calculate the expected numbers of unmarked fish at risk of capture. By using information from both marked and unmarked animals in a standard fisheries age structure framework, this approach is well suited to the sparse data situations common in long-term capture-recapture programs with variable sampling effort. ?? Copyright by the American Fisheries Society 2006.

  8. A Comparison of the Lower Stratospheric Age-Spectra Derived from a General Circulation Model and Two Data Assimilation Systems

    NASA Technical Reports Server (NTRS)

    Schoeberl, Mark R.; Douglass, Anne R.; Zhu, Zhengxin; Pawson, Steven

    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 isolated tropics in good agreement with observations; however, the age spectra determined from the DAS differ from the GCM spectra. For the DAS diabatic trajectory calculations there is too much exchange between the tropics and mid-latitudes. The age spectrum is thus too broad and the tropical mean age is too old as a result of mixing older mid latitude air with tropical air. Likewise the mid latitude mean age is too young due to the in mixing of tropical air. The DAS kinematic trajectory calculations show excessive vertical dispersion of parcels in addition to excessive exchange between the tropics and mid latitudes. Because air is moved rapidly to the troposphere from the vertical dispersion, the age spectrum is shifted toward the young side. The excessive vertical and meridional dispersion compensate in the kinematic case giving a reasonable tropical mean age. The CTM calculation of the age spectrum using the DAS winds shows the same vertical and meridional 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 extra tropical 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. These anomalies can be linked to year-to-year variations in the tropical heating rate. The anomalies are

  9. [Current model of breakfast for different age groups: children, a adolescents and adults].

    PubMed

    Núñez, C; Cuadrado, C; Carbajal, A; Moreiras, O

    1998-01-01

    The objective of the present work is to assess the current breakfast model in different age groups: children between the ages of 6 and 12 years (n = 54); adolescents between the ages of 13 and 17 years (n = 174); and adults, older than 18 years of age (n = 252). For this a questionnaire has been designed that follows the standards of that used for a similar study by our team in 1984 on a sample of 1350 individuals. The modified and amplified questionnaire included open and closed questions about: the omission of breakfast and its causes, foods that are a part of breakfast, the most frequent types and the variations, the role of the second breakfast, the number of fasting hours since dinner, the time spent of breakfast, and the subjective opinion regarding the importance or not of having breakfast. 98.95% answer yes to the question do you have breakfast, but only 9% eats a nutritionally correct breakfast, one defined as that breakfast that supplies 20% of the total energy and includes foods from at least four different groups. All the children included some form of milk product in their breakfast. The adolescents consumed the lowest proportion of cereals (19.4%) and the highest proportion of pastries (24.2%). The percentage of adults who drink coffee with milk (57%) and sugar (37.7%) is significantly higher than that it the other two groups. Bread (37.7%), pastries (28.3%) and cookies (26.1%) are the solid foods eaten most by the adults. The children spend the longest time on breakfast. 35.9% of the sample varies their breakfast, 43.1% never does, and 21% does so sometimes. The average time elapsed between dinner and breakfast is 10.5 +/- 1.2 hours. It is advisable to have a more nutritionally balanced breakfast, including different foods from at least four groups, and including a greater variety in the menus. PMID:9780752

  10. The aging mouse partially models the aging human spine: lumbar and coccygeal disc height, composition, mechanical properties, and Wnt signaling in young and old mice

    PubMed Central

    Aguilar, Rhiannon; Harland, Robin A.; Bomar, Bradley A.; Silva, Matthew J.

    2014-01-01

    Murine lumbar and coccygeal (tail) regions of spines are commonly used to study cellular signaling of age-related disc diseases, but the tissue-level changes of aging intervertebral discs and vertebrae of each spinal region remain unclear. Furthermore, the impact of aging lumbar and coccygeal discs on Wnt/β-catenin signaling, which is putatively involved in the catabolism of intervertebral discs, is also unclear. We compared disc/vertebrae morphology and mechanics and biochemical composition of intervertebral discs from lumbar and coccygeal regions between young (4–5 mo) and old (20–22 mo) female C57BL/6 mice. Center intervertebral disc height from both regions was greater in old discs than young discs. Compared with young, old lumbar discs had a lower early viscous coefficient (a measure of stiffness) by 40%, while conversely old coccygeal discs were stiffer by 53%. Biochemically, old mice had double the collagen content in lumbar and coccygeal discs of young discs, greater glycosaminoglycan in lumbar discs by 37%, but less glycosaminoglycan in coccygeal discs by 32%. Next, we compared Wnt activity of lumbar and coccygeal discs of 4- to 5-mo and 12- to 14-mo TOPGAL mice. Despite the disc-specific changes, aging decreased Wnt signaling in the nucleus pulposus from both spinal regions by ≥64%. Compared with young, trabecular bone volume/tissue volume and ultimate force were less in old lumbar vertebrae, but greater in old coccygeal vertebrae. Thus intervertebral discs and vertebrae age in a spinal region-dependent manner, but these differential age-related changes may be uncoupled from Wnt signaling. Overall, lumbar and coccygeal regions are not interchangeable in modeling human aging. PMID:24790018

  11. Numerical Modeling of the Last Glacial Maximum Yellowstone Ice Cap Captures Asymmetry in Moraine Ages

    NASA Astrophysics Data System (ADS)

    Anderson, L. S.; Wickert, A. D.; Colgan, W. T.; Anderson, R. S.

    2014-12-01

    The Last Glacial Maximum (LGM) Yellowstone Ice Cap was the largest continuous ice body in the US Rocky Mountains. Terminal moraine ages derived from cosmogenic radionuclide dating (e.g., Licciardi and Pierce, 2008) constrain the timing of maximum Ice Cap extent. Importantly, the moraine ages vary by several thousand years around the Ice Cap; ages on the eastern outlet glaciers are significantly younger than their western counterparts. In order to interpret these observations within the context of LGM climate in North America, we perform two numerical glacier modeling experiments: 1) We model the initiation and growth of the Ice Cap to steady state; and 2) We estimate the range of LGM climate states which led to the formation of the Ice Cap. We use an efficient semi-implicit 2-D glacier model coupled to a fully implicit solution for flexural isostasy, allowing for transient links between climatic forcing, ice thickness, and earth surface deflection. Independent of parameter selection, the Ice Cap initiates in the Absaroka and Beartooth mountains and then advances across the Yellowstone plateau to the west. The Ice Cap advances to its maximum extent first to the older eastern moraines and last to the younger western and northwestern moraines. This suggests that the moraine ages may reflect the timescale required for the Ice Cap to advance across the high elevation Yellowstone plateau rather than the timing of local LGM climate. With no change in annual precipitation from the present, a mean summer temperature drop of 8-9° C is required to form the Ice Cap. Further parameter searches provide the full range of LGM paleoclimate states that led to the Yellowstone Ice Cap. Using our preferred parameter set, we find that the timescale for the growth of the complete Ice Cap is roughly 10,000 years. Isostatic subsidence helps explain the long timescale of Ice Cap growth. The Yellowstone Ice Cap caused a maximum surface deflection of 300 m (using a constant effective elastic

  12. Age model for a continuous, ca 250-ka Quaternary lacustrine record from Bear Lake, Utah-Idaho

    USGS Publications Warehouse

    Colman, Steven M.; Kaufman, D.S.; Bright, Jordon; Heil, C.; King, J.W.; Dean, W.E.; Rosenbaum, J.G.; Forester, R.M.; Bischoff, J.L.; Perkins, Marie; McGeehin, J.P.

    2006-01-01

    The Quaternary sediments sampled by continuous 120-m-long drill cores from Bear Lake (Utah-Idaho) comprise one of the longest lacustrine sequences recovered from an extant lake. The cores serve as a good case study for the construction of an age model for sequences that extend beyond the range of radiocarbon dating. From a variety of potential age indicators, we selected a combination of radiocarbon ages, one magnetic excursion (correlated to a standard sequence), and a single Uranium-series age to develop an initial data set. The reliability of the excursion and U-series data require consideration of their position with respect to sediments of inferred interglacial character, but not direct correlation with other paleoclimate records. Data omitted from the age model include amino acid age estimates, which have a large amount of scatter, and tephrochronology correlations, which have relatively large uncertainties. Because the initial data set was restricted to the upper half of the BL00-1 core, we inferred additional ages by direct correlation to the independently dated paleoclimate record from Devils Hole. We developed an age model for the entire core using statistical methods that consider both the uncertainties of the original data and that of the curve-fitting process, with a combination of our initial data set and the climate correlations as control points. This age model represents our best estimate of the chronology of deposition in Bear Lake. Because the age model contains assumptions about the correlation of Bear Lake to other climate records, the model cannot be used to address some paleoclimate questions, such as phase relationships with other areas.

  13. Little Ice Age glaciers in Britain: Glacier–climate modelling in the Cairngorm Mountains

    SciTech Connect

    Stephan Harrison; Ann V. Rowan; Neil F. Glasser; Jasper Knight; Mitchell A. Plummer; Stephanie C. Mills

    2014-02-01

    It is widely believed that the last glaciers in the British Isles disappeared at the end of the Younger Dryas stadial (12.9–11.7 cal. kyr BP). Here, we use a glacier–climate model driven by data from local weather stations to show for the first time that glaciers developed during the Little Ice Age (LIA) in the Cairngorm Mountains. Our model is forced from contemporary conditions by a realistic difference in mean annual air temperature of -1.5 degrees C and an increase in annual precipitation of 10%, and confirmed by sensitivity analyses. These results are supported by the presence of small boulder moraines well within Younger Dryas ice limits, and by a dating programme on a moraine in one cirque. As a result, we argue that the last glaciers in the Cairngorm Mountains (and perhaps elsewhere in upland Britain) existed in the LIA within the last few hundred years, rather than during the Younger Dryas.

  14. Normal forms for semilinear equations with non-dense domain with applications to age structured models

    NASA Astrophysics Data System (ADS)

    Liu, Zhihua; Magal, Pierre; Ruan, Shigui

    2014-08-01

    Normal form theory is very important and useful in simplifying the forms of equations restricted on the center manifolds in studying nonlinear dynamical problems. In this paper, using the center manifold theorem associated with the integrated semigroup theory, we develop a normal form theory for semilinear Cauchy problems in which the linear operator is not densely defined and is not a Hille-Yosida operator and present procedures to compute the Taylor expansion and normal form of the reduced system restricted on the center manifold. We then apply the main results and computation procedures to determine the direction of the Hopf bifurcation and stability of the bifurcating periodic solutions in a structured evolutionary epidemiological model of influenza A drift and an age structured population model.

  15. Parameterizing age patterns of demographic rates with the multiexponential model schedule.

    PubMed

    Rogers, A; Little, J S

    1994-02-01

    "For nearly 200 years actuaries, statisticians, and demographers have sought to summarize the age pattern of mortality rates by means of a limited number of parameters. Such 'model schedules' have also been useful in representing schedules of rates other than mortality....This paper illustrates a particular general functional form for such model schedules: the multiexponential function. It discusses the changing behavior of this function as its parameters take on different values and examines the quality of the fits of this function to observed data on mortality, fertility, and migration." This is a revised version of a paper originally presented at the 1993 Annual Meeting of the Population Association of America. (SUMMARY IN FRE) PMID:12287088

  16. The structure of horizontal-branch models. I - The zero-age horizontal branch

    NASA Technical Reports Server (NTRS)

    Dorman, Ben

    1992-01-01

    A detailed study of the structure of zero-age horizontal-branch (ZAHB) models is studied in order to show how the hydrostatic structure of these models changes with the input parameters and determines the H-R diagram location of a given model. The properties of composite polytropes on the homology-invariant (U,V)-plane are demonstrated. A variety of test models and sequences were constructed to elucidate the underlying factors that give rise to the wide variation in HB model properties with composition. The roles of the CNO elements as nuclear catalysts and of the envelope sources, as well as the envelope helium abundance are reexamined. It is found that, for stars of a fixed range of mass arriving on the HB, the stellar distribution is determined mainly by CNO for low metallicities (Fe/H of less than about -1), but mainly by opacity sources for high metallicities. The value of Fe/H where CNO ceases to dominate depends significantly on the adopted opacity and will decrease if and when opacity estimates are revised upward.

  17. Infant Gaze Following and Pointing Predict Accelerated Vocabulary Growth through Two Years of Age: A Longitudinal, Growth Curve Modeling Study

    ERIC Educational Resources Information Center

    Brooks, Rechele; Meltzoff, Andrew N.

    2008-01-01

    We found that infant gaze following and pointing predicts subsequent language development. At ages 0 ; 10 or 0 ; 11, infants saw an adult turn to look at an object in an experimental setting. Productive vocabulary was assessed longitudinally through two years of age. Growth curve modeling showed that infants who gaze followed and looked longer at…

  18. Effects of Extrinsic Mortality on the Evolution of Aging: A Stochastic Modeling Approach

    PubMed Central

    Shokhirev, Maxim Nikolaievich; Johnson, Adiv Adam

    2014-01-01

    The evolutionary theories of aging are useful for gaining insights into the complex mechanisms underlying senescence. Classical theories argue that high levels of extrinsic mortality should select for the evolution of shorter lifespans and earlier peak fertility. Non-classical theories, in contrast, posit that an increase in extrinsic mortality could select for the evolution of longer lifespans. Although numerous studies support the classical paradigm, recent data challenge classical predictions, finding that high extrinsic mortality can select for the evolution of longer lifespans. To further elucidate the role of extrinsic mortality in the evolution of aging, we implemented a stochastic, agent-based, computational model. We used a simulated annealing optimization approach to predict which model parameters predispose populations to evolve longer or shorter lifespans in response to increased levels of predation. We report that longer lifespans evolved in the presence of rising predation if the cost of mating is relatively high and if energy is available in excess. Conversely, we found that dramatically shorter lifespans evolved when mating costs were relatively low and food was relatively scarce. We also analyzed the effects of increased predation on various parameters related to density dependence and energy allocation. Longer and shorter lifespans were accompanied by increased and decreased investments of energy into somatic maintenance, respectively. Similarly, earlier and later maturation ages were accompanied by increased and decreased energetic investments into early fecundity, respectively. Higher predation significantly decreased the total population size, enlarged the shared resource pool, and redistributed energy reserves for mature individuals. These results both corroborate and refine classical predictions, demonstrating a population-level trade-off between longevity and fecundity and identifying conditions that produce both classical and non

  19. IODP Expedition 351 Izu-Bonin-Mariana Arc Origins: Age model for Site U1438

    NASA Astrophysics Data System (ADS)

    Morris, Antony; Maffione, Marco; Kender, Sev; Aljahdali, Mohammed; Bandini, Alexandre; Guerra, Rodrigo do Monte

    2015-04-01

    We report preliminary paleomagnetic and paleontological results from International Ocean Discovery Program (IODP) Expedition 351, which recovered an unprecedented ~1.4 km thick volcaniclastic sedimentary record documenting the initiation and subsequent evolution of the Izu-Bonin-Mariana (IBM) intra-oceanic arc-basin system. Magnetostratigraphic and biostratigraphic constraints provide a high-resolution temporal framework for interpretation of this record. Paleomagnetic analyses of archive half core samples provide a continuous record of the geomagnetic field inclination down to 847 mbsf that allows construction of a detailed site magnetostratigraphy that closely matches the Geomagnetic Polarity Timescale (Gradstein et al., 2012). A total of 87 geomagnetic reversals have been recognized in the studied succession, extending back to ~36 Ma. Despite sporadic microfossil occurrences in parts, calcareous nannofossils, planktonic foraminifera and radiolarians each contribute to the age model for the entire Site. All nannofossil marker species for Oligocene to Eocene Zones NP25 to NP19/20 are recognised. Beneath paleomagnetic control (847-1449 mbsf), foraminifera and radiolarians provide the only age control. The most salient features of the age model are that: (i) average linear sedimentation rates during the Plio-Pleistocene range from 1.4 to 2.2 cm/ka; (ii) there was a reduction in sedimentation rates to 0.25 - 0.5 cm/ka throughout the Miocene; and (iii) sedimentation rates sharply increase again in the Oligocene to Late Eocene to a maximum of ~20 cm/ka. These quantitative constraints closely match (non-quantitative) inferences based on the lithostratigraphy of the site, with fine-grained/coarse-grained sediments dominating in periods with low/high sedimentation rates respectively.

  20. IODP Expedition 351 Izu-Bonin-Mariana Arc Origins: Age Model for Site U1438

    NASA Astrophysics Data System (ADS)

    Morris, A.; Aljahdali, M. H.; Bandini, A. N.; do Monte Guerra, R.; Kender, S.; Maffione, M.

    2014-12-01

    We report preliminary paleomagnetic and paleontological results from International Ocean Discovery Program (IODP) Expedition 351, which recovered an unprecedented ~1.4 km thick volcaniclastic sedimentary record documenting the initiation and subsequent evolution of the Izu-Bonin-Mariana (IBM) intra-oceanic arc-basin system. Magnetostratigraphic and biostratigraphic constraints provide a high-resolution temporal framework for interpretation of this record.Paleomagnetic analyses of archive half core samples provide a continuous record of the geomagnetic field inclination down to 847 mbsf that allows construction of a detailed site magnetostratigraphy that closely matches the Geomagnetic Polarity Timescale (Gradstein et al., 2012). A total of 87 geomagnetic reversals have been recognized in the studied succession, extending back to ~36 Ma. Despite sporadic microfossil occurrences in parts, calcareous nannofossils, planktonic foraminifera and radiolarians each contribute to the age model for the entire Site. All nannofossil marker species for Oligocene to Eocene Zones NP25 to NP19/20 are recognised. Beneath paleomagnetic control (847-1449 mbsf), foraminifera and radiolarians provide the only age control.The most salient features of the age model are that: (i) average linear sedimentation rates during the Plio-Pleistocene range from 1.4 to 2.2 cm/ka; (ii) there was a reduction in sedimentation rates to 0.25 - 0.5 cm/ka throughout the Miocene; and (iii) sedimentation rates sharply increase again in the Oligocene to Late Eocene to a maximum of ~20 cm/ka. These quantitative constraints closely match (non-quantitative) inferences based on the lithostratigraphy of the site, with fine-grained/coarse-grained sediments dominating in periods with low/high sedimentation rates respectively.

  1. Retinal Ultrastructure of Murine Models of Dry Age-related Macular Degeneration (AMD)

    PubMed Central

    Ramkumar, Hema L.; Zhang, Jun; Chan, Chi-Chao

    2010-01-01

    Age-related macular degeneration (AMD) is the most prevalent form of irreversible blindness worldwide in the elderly population. The pathology of dry AMD consists of degeneration of photoreceptors and the RPE, lipofuscin (A2E) accumulation, and drusen formation. Mice have been widely used for generating models that simulate human AMD features for investigating the pathogenesis, treatment and prevention of the disease. Although the mouse has no macula, focal atrophy of photorecptors and RPE, lipofuscin accumulation, and increased A2E can develop in aged mouse eyes. However, drusen are rarely seen in mice because of their simpler Bruch’s membrane and different process of lipofuscin extrusion compared with humans. Thus, analyzing basal deposits at the ultrastructural level and understanding the ultrastructural pathologic differences between various mouse AMD models are critical to comprehending the significance of research findings and response to possible therapeutic options for dry AMD. Based o