Science.gov

Sample records for ageing model podospora

  1. The autophagy interaction network of the aging model Podospora anserina.

    PubMed

    Philipp, Oliver; Hamann, Andrea; Osiewacz, Heinz D; Koch, Ina

    2017-03-27

    Autophagy is a conserved molecular pathway involved in the degradation and recycling of cellular components. It is active either as response to starvation or molecular damage. Evidence is emerging that autophagy plays a key role in the degradation of damaged cellular components and thereby affects aging and lifespan control. In earlier studies, it was found that autophagy in the aging model Podospora anserina acts as a longevity assurance mechanism. However, only little is known about the individual components controlling autophagy in this aging model. Here, we report a biochemical and bioinformatics study to detect the protein-protein interaction (PPI) network of P. anserina combining experimental and theoretical methods. We constructed the PPI network of autophagy in P. anserina based on the corresponding networks of yeast and human. We integrated PaATG8 interaction partners identified in an own yeast two-hybrid analysis using ATG8 of P. anserina as bait. Additionally, we included age-dependent transcriptome data. The resulting network consists of 89 proteins involved in 186 interactions. We applied bioinformatics approaches to analyze the network topology and to prove that the network is not random, but exhibits biologically meaningful properties. We identified hub proteins which play an essential role in the network as well as seven putative sub-pathways, and interactions which are likely to be evolutionary conserved amongst species. We confirmed that autophagy-associated genes are significantly often up-regulated and co-expressed during aging of P. anserina. With the present study, we provide a comprehensive biological network of the autophagy pathway in P. anserina comprising PPI and gene expression data. It is based on computational prediction as well as experimental data. We identified sub-pathways, important hub proteins, and evolutionary conserved interactions. The network clearly illustrates the relation of autophagy to aging processes and enables

  2. Identification of autophagy as a longevity-assurance mechanism in the aging model Podospora anserina.

    PubMed

    Knuppertz, Laura; Hamann, Andrea; Pampaloni, Francesco; Stelzer, Ernst; Osiewacz, Heinz D

    2014-05-01

    The filamentous ascomycete Podospora anserina is a well-established aging model in which a variety of different pathways, including those involved in the control of respiration, ROS generation and scavenging, DNA maintenance, proteostasis, mitochondrial dynamics, and programmed cell death have previously been demonstrated to affect aging and life span. Here we address a potential role of autophagy. We provide data demonstrating high basal autophagy levels even in strains cultivated under noninduced conditions. By monitoring an N-terminal fusion of EGFP to the fungal LC3 homolog PaATG8 over the lifetime of the fungus on medium with and without nitrogen supplementation, respectively, we identified a significant increase of GFP puncta in older and in nitrogen-starved cultures suggesting an induction of autophagy during aging. This conclusion is supported by the demonstration of an age-related and autophagy-dependent degradation of a PaSOD1-GFP reporter protein. The deletion of Paatg1, which leads to the lack of the PaATG1 serine/threonine kinase active in early stages of autophagy induction, impairs ascospore germination and development and shortens life span. Under nitrogen-depleted conditions, life span of the wild type is increased almost 4-fold. In contrast, this effect is annihilated in the Paatg1 deletion strain, suggesting that the ability to induce autophagy is beneficial for this fungus. Collectively, our data identify autophagy as a longevity-assurance mechanism in P. anserina and as another surveillance pathway in the complex network of pathways affecting aging and development. These findings provide perspectives for the elucidation of the mechanisms involved in the regulation of individual pathways and their interactions.

  3. Identification of autophagy as a longevity-assurance mechanism in the aging model Podospora anserina

    PubMed Central

    Knuppertz, Laura; Hamann, Andrea; Pampaloni, Francesco; Stelzer, Ernst; Osiewacz, Heinz D

    2014-01-01

    The filamentous ascomycete Podospora anserina is a well-established aging model in which a variety of different pathways, including those involved in the control of respiration, ROS generation and scavenging, DNA maintenance, proteostasis, mitochondrial dynamics, and programmed cell death have previously been demonstrated to affect aging and life span. Here we address a potential role of autophagy. We provide data demonstrating high basal autophagy levels even in strains cultivated under noninduced conditions. By monitoring an N-terminal fusion of EGFP to the fungal LC3 homolog PaATG8 over the lifetime of the fungus on medium with and without nitrogen supplementation, respectively, we identified a significant increase of GFP puncta in older and in nitrogen-starved cultures suggesting an induction of autophagy during aging. This conclusion is supported by the demonstration of an age-related and autophagy-dependent degradation of a PaSOD1-GFP reporter protein. The deletion of Paatg1, which leads to the lack of the PaATG1 serine/threonine kinase active in early stages of autophagy induction, impairs ascospore germination and development and shortens life span. Under nitrogen-depleted conditions, life span of the wild type is increased almost 4-fold. In contrast, this effect is annihilated in the Paatg1 deletion strain, suggesting that the ability to induce autophagy is beneficial for this fungus. Collectively, our data identify autophagy as a longevity-assurance mechanism in P. anserina and as another surveillance pathway in the complex network of pathways affecting aging and development. These findings provide perspectives for the elucidation of the mechanisms involved in the regulation of individual pathways and their interactions. PMID:24584154

  4. A potential impact of DNA repair on ageing and lifespan in the ageing model organism Podospora anserina: decrease in mitochondrial DNA repair activity during ageing.

    PubMed

    Soerensen, Mette; Gredilla, Ricardo; Müller-Ohldach, Mathis; Werner, Alexandra; Bohr, Vilhelm A; Osiewacz, Heinz D; Stevnsner, Tinna

    2009-08-01

    The free radical theory of ageing states that ROS play a key role in age-related decrease in mitochondrial function via the damage of mitochondrial DNA (mtDNA), proteins and lipids. In the sexually reproducing ascomycete Podospora anserina ageing is, as in other eukaryotes, associated with mtDNA instability and mitochondrial dysfunction. Part of the mtDNA instabilities may arise due to accumulation of ROS induced mtDNA lesions, which, as previously suggested for mammals, may be caused by an age-related decrease in base excision repair (BER). Alignments of known BER protein sequences with the P. anserina genome revealed high homology. We report for the first time the presence of BER activities in P. anserina mitochondrial extracts. DNA glycosylase activities decrease with age, suggesting that the increased mtDNA instability with age may be caused by decreased ability to repair mtDNA damage and hence contribute to ageing and lifespan control in this ageing model. Additionally, we find low DNA glycosylase activities in the long-lived mutants grisea and DeltaPaCox17::ble, which are characterized by low mitochondrial ROS generation. Overall, our data identify a potential role of mtDNA repair in controlling ageing and life span in P. anserina, a mechanism possibly regulated in response to ROS levels.

  5. A potential impact of DNA repair on ageing and lifespan in the ageing model organism Podospora anserina: Decrease in mitochondrial DNA repair activity during ageing

    PubMed Central

    Soerensen, Mette; Gredilla, Ricardo; Müller-Ohldach, Mathis; Werner, Alexandra; Bohr, Vilhelm A.; Osiewacz, Heinz D.; Stevnsner, Tinna

    2009-01-01

    Summary The free radical theory of ageing states that ROS play a key role in age-related decrease in mitochondrial function via the damage of mitochondrial DNA (mtDNA), proteins and lipids. In the sexually reproducing ascomycete Podospora anserina ageing is, as in other eukaryotes, associated with mtDNA instability and mitochondrial dysfunction. Part of the mtDNA instabilities may arise due to accumulation of ROS induced mtDNA lesions, which, as previously suggested for mammals, may be caused by an age-related decrease in base excision repair (BER). Alignments of known BER protein sequences with the P. anserina genome revealed high homology. We report for the first time the presence of BER activities in P. anserina mitochondrial extracts. DNA glycosylase activities decrease with age, suggesting that the increased mtDNA instability with age may be caused by decreased ability to repair mtDNA damage and hence contribute to ageing and lifespan control in this ageing model. Additionally, we find low DNA glycosylase activities in the long-lived mutants grisea and ΔPaCox17∷ble, which are characterized by among others low mitochondrial ROS generation. Overall, our data identify a potential role of mtDNA repair in controlling ageing and life span in P. anserina, a mechanism possibly regulated in response to ROS levels. PMID:19486911

  6. The genome sequence of the model ascomycete fungus Podospora anserina.

    PubMed

    Espagne, Eric; Lespinet, Olivier; Malagnac, Fabienne; Da Silva, Corinne; Jaillon, Olivier; Porcel, Betina M; Couloux, Arnaud; Aury, Jean-Marc; Ségurens, Béatrice; Poulain, Julie; Anthouard, Véronique; Grossetete, Sandrine; Khalili, Hamid; Coppin, Evelyne; Déquard-Chablat, Michelle; Picard, Marguerite; Contamine, Véronique; Arnaise, Sylvie; Bourdais, Anne; Berteaux-Lecellier, Véronique; Gautheret, Daniel; de Vries, Ronald P; Battaglia, Evy; Coutinho, Pedro M; Danchin, Etienne Gj; Henrissat, Bernard; Khoury, Riyad El; Sainsard-Chanet, Annie; Boivin, Antoine; Pinan-Lucarré, Bérangère; Sellem, Carole H; Debuchy, Robert; Wincker, Patrick; Weissenbach, Jean; Silar, Philippe

    2008-01-01

    The dung-inhabiting ascomycete fungus Podospora anserina is a model used to study various aspects of eukaryotic and fungal biology, such as ageing, prions and sexual development. We present a 10X draft sequence of P. anserina genome, linked to the sequences of a large expressed sequence tag collection. Similar to higher eukaryotes, the P. anserina transcription/splicing machinery generates numerous non-conventional transcripts. Comparison of the P. anserina genome and orthologous gene set with the one of its close relatives, Neurospora crassa, shows that synteny is poorly conserved, the main result of evolution being gene shuffling in the same chromosome. The P. anserina genome contains fewer repeated sequences and has evolved new genes by duplication since its separation from N. crassa, despite the presence of the repeat induced point mutation mechanism that mutates duplicated sequences. We also provide evidence that frequent gene loss took place in the lineages leading to P. anserina and N. crassa. P. anserina contains a large and highly specialized set of genes involved in utilization of natural carbon sources commonly found in its natural biotope. It includes genes potentially involved in lignin degradation and efficient cellulose breakdown. The features of the P. anserina genome indicate a highly dynamic evolution since the divergence of P. anserina and N. crassa, leading to the ability of the former to use specific complex carbon sources that match its needs in its natural biotope.

  7. The genome sequence of the model ascomycete fungus Podospora anserina

    PubMed Central

    Espagne, Eric; Lespinet, Olivier; Malagnac, Fabienne; Da Silva, Corinne; Jaillon, Olivier; Porcel, Betina M; Couloux, Arnaud; Aury, Jean-Marc; Ségurens, Béatrice; Poulain, Julie; Anthouard, Véronique; Grossetete, Sandrine; Khalili, Hamid; Coppin, Evelyne; Déquard-Chablat, Michelle; Picard, Marguerite; Contamine, Véronique; Arnaise, Sylvie; Bourdais, Anne; Berteaux-Lecellier, Véronique; Gautheret, Daniel; de Vries, Ronald P; Battaglia, Evy; Coutinho, Pedro M; Danchin, Etienne GJ; Henrissat, Bernard; Khoury, Riyad EL; Sainsard-Chanet, Annie; Boivin, Antoine; Pinan-Lucarré, Bérangère; Sellem, Carole H; Debuchy, Robert; Wincker, Patrick; Weissenbach, Jean; Silar, Philippe

    2008-01-01

    Background The dung-inhabiting ascomycete fungus Podospora anserina is a model used to study various aspects of eukaryotic and fungal biology, such as ageing, prions and sexual development. Results We present a 10X draft sequence of P. anserina genome, linked to the sequences of a large expressed sequence tag collection. Similar to higher eukaryotes, the P. anserina transcription/splicing machinery generates numerous non-conventional transcripts. Comparison of the P. anserina genome and orthologous gene set with the one of its close relatives, Neurospora crassa, shows that synteny is poorly conserved, the main result of evolution being gene shuffling in the same chromosome. The P. anserina genome contains fewer repeated sequences and has evolved new genes by duplication since its separation from N. crassa, despite the presence of the repeat induced point mutation mechanism that mutates duplicated sequences. We also provide evidence that frequent gene loss took place in the lineages leading to P. anserina and N. crassa. P. anserina contains a large and highly specialized set of genes involved in utilization of natural carbon sources commonly found in its natural biotope. It includes genes potentially involved in lignin degradation and efficient cellulose breakdown. Conclusion The features of the P. anserina genome indicate a highly dynamic evolution since the divergence of P. anserina and N. crassa, leading to the ability of the former to use specific complex carbon sources that match its needs in its natural biotope. PMID:18460219

  8. Genetic control of anastomosis in Podospora anserina.

    PubMed

    Tong, Laetitia Chan Ho; Silar, Philippe; Lalucque, Hervé

    2014-09-01

    We developed a new microscopy procedure to study anastomoses in the model ascomycete Podospora anserina and compared it with the previous method involving the formation of balanced heterokaryons. Both methods showed a good correlation. Heterokaryon formation was less quantifiable, but enabled to observe very rare events. Microscopic analysis evidenced that anastomoses were greatly influence by growth conditions and were severely impaired in the IDC mutants of the PaMpk1, PaMpk2, IDC1 and PaNox1 pathways. Yet some mutants readily formed heterokaryons, albeit with a delay when compared to the wild type. We also identified IDC(821), a new mutant presenting a phenotype similar to the other IDC mutants, including lack of anastomosis. Complete genome sequencing revealed that IDC(821) was affected in the orthologue of the Neurospora crassa So gene known to control anastomosis in several other ascomycetes.

  9. Manganese rescues adverse effects on lifespan and development in Podospora anserina challenged by excess hydrogen peroxide.

    PubMed

    Grimm, Carolin; Osiewacz, Heinz D

    2015-03-01

    For biological systems, balancing cellular levels of reactive oxygen species (ROS) is of great importance because ROS are both, essential for cellular signaling and dangerous in causing molecular damage. Cellular ROS abundance is controlled by a delicate network of molecular pathways. Within this network, superoxide dismutases (SODs) are active in disproportion of the superoxide anion leading to the formation of hydrogen peroxide. The fungal aging model Podospora anserina encodes at least three SODs. One of these is the mitochondrial PaSOD3 isoform containing manganese as a cofactor. Previous work resulted in the selection of strains in which PaSod3 is strongly overexpressed. These strains display impairments in growth and lifespan. A computational model suggests a series of events to occur in Sod3 overexpressing strains leading to adverse effects due to elevated hydrogen peroxide levels. In an attempt to validate this model and to obtain more detailed information about the cellular responses involved in ROS balancing, we further investigated the PaSod3 overexpressing strains. Here we show that hydrogen peroxide levels are indeed strongly increased in the mutant strain. Surprisingly, this phenotype can be rescued by the addition of manganese to the growth medium. Strikingly, while we obtained no evidence for an antioxidant effect of manganese, we found that the metal is required for induction of components of the ROS scavenging network and lowers the hydrogen peroxide level of the mutant. A similar effect of manganese on lifespan reversion was obtained in wild-type strains challenged with exogenous hydrogen peroxide. It appears that manganese is limited under high hydrogen peroxide and suggests that a manganese-dependent activity leads to the induction of ROS scavenging components. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Ribosomal suppressors and antisuppressors in Podospora anserina: resistance to cycloheximide.

    PubMed Central

    Coppin-Raynal, E

    1977-01-01

    Informational suppressors and antisuppressors have been previously isolated in Podospora anserina, and a range of exclusively genetic arguments have led to the assumption that they correspond to ribosomal mutations. An in vivo and in vitro comparison of the effect of the ribosomal inhibitor cycloheximide on wildtype and mutant strains described in this paper confirms the ribosomal hypothesis for at least some mutants. Indeed, the four mutants in the AS3 gene were cycloheximide resistant, and their ribosomes were found to be resistant when analyzed by polyuridyl-directed polyphenylalanine systhesis. On the other hand, ribosomes from two su 1 mutants were hypersensitive to the drug. PMID:893344

  11. 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.

  12. The Transcriptional Response to Nonself in the Fungus Podospora anserina

    PubMed Central

    Bidard, Frédérique; Clavé, Corinne; Saupe, Sven J.

    2013-01-01

    In fungi, heterokaryon incompatibility is a nonself recognition process occurring when filaments of different isolates of the same species fuse. Compatibility is controlled by so-called het loci and fusion of strains of unlike het genotype triggers a complex incompatibility reaction that leads to the death of the fusion cell. Herein, we analyze the transcriptional changes during the incompatibility reaction in Podospora anserina. The incompatibility response was found to be associated with a massive transcriptional reprogramming: 2231 genes were up-regulated by a factor 2 or more during incompatibility. In turn, 2441 genes were down-regulated. HET, NACHT, and HeLo domains previously found to be involved in the control of heterokaryon incompatibility were enriched in the up-regulated gene set. In addition, incompatibility was characterized by an up-regulation of proteolytic and other hydrolytic activities, of secondary metabolism clusters and toxins and effector-like proteins. The up-regulated set was found to be enriched for proteins lacking orthologs in other species and chromosomal distribution of the up-regulated genes was uneven with up-regulated genes residing preferentially in genomic islands and on chromosomes IV and V. There was a significant overlap between regulated genes during incompatibility in P. anserina and Neurospora crassa, indicating similarities in the incompatibility responses in these two species. Globally, this study illustrates that the expression changes occurring during cell fusion incompatibility in P. anserina are in several aspects reminiscent of those described in host-pathogen or symbiotic interactions in other fungal species. PMID:23589521

  13. 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

  14. 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

  15. 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

  16. Alachalasins A-G, new cytochalasins from the fungus Stachybotrys Podospora vesticola [corrected].

    PubMed

    Zhang, Yonggang; Tian, Renrong; Liu, Shuchun; Chen, Xulin; Liu, Xingzhong; Che, Yongsheng

    2008-03-01

    Alachalasins A-G (1-7), seven new cytochalasin-type of metabolites, have been isolated from cultures of an isolate of Stachybotrys Podospora vesticola [corrected] The structures of these compounds were determined mainly by analysis of their NMR spectroscopic data, and the absolute configuration of 1 was assigned by application of the modified Mosher method. Alachalasin A (1) displayed inhibitory effect on HIV-1LAI replication in C8166 cells with an EC50 of 8.01 microM; alachalasins D (4) and G (7) showed modest antimicrobial activity.

  17. Modeled ground water age distributions

    USGS Publications Warehouse

    Woolfenden, Linda R.; Ginn, Timothy R.

    2009-01-01

    The age of ground water in any given sample is a distributed quantity representing distributed provenance (in space and time) of the water. Conventional analysis of tracers such as unstable isotopes or anthropogenic chemical species gives discrete or binary measures of the presence of water of a given age. Modeled ground water age distributions provide a continuous measure of contributions from different recharge sources to aquifers. A numerical solution of the ground water age equation of Ginn (1999) was tested both on a hypothetical simplified one-dimensional flow system and under real world conditions. Results from these simulations yield the first continuous distributions of ground water age using this model. Complete age distributions as a function of one and two space dimensions were obtained from both numerical experiments. Simulations in the test problem produced mean ages that were consistent with the expected value at the end of the model domain for all dispersivity values tested, although the mean ages for the two highest dispersivity values deviated slightly from the expected value. Mean ages in the dispersionless case also were consistent with the expected mean ages throughout the physical model domain. Simulations under real world conditions for three dispersivity values resulted in decreasing mean age with increasing dispersivity. This likely is a consequence of an edge effect. However, simulations for all three dispersivity values tested were mass balanced and stable demonstrating that the solution of the ground water age equation can provide estimates of water mass density distributions over age under real world conditions.

  18. Modeled ground water age distributions.

    PubMed

    Woolfenden, Linda R; Ginn, Timothy R

    2009-01-01

    The age of ground water in any given sample is a distributed quantity representing distributed provenance (in space and time) of the water. Conventional analysis of tracers such as unstable isotopes or anthropogenic chemical species gives discrete or binary measures of the presence of water of a given age. Modeled ground water age distributions provide a continuous measure of contributions from different recharge sources to aquifers. A numerical solution of the ground water age equation of Ginn (1999) was tested both on a hypothetical simplified one-dimensional flow system and under real world conditions. Results from these simulations yield the first continuous distributions of ground water age using this model. Complete age distributions as a function of one and two space dimensions were obtained from both numerical experiments. Simulations in the test problem produced mean ages that were consistent with the expected value at the end of the model domain for all dispersivity values tested, although the mean ages for the two highest dispersivity values deviated slightly from the expected value. Mean ages in the dispersionless case also were consistent with the expected mean ages throughout the physical model domain. Simulations under real world conditions for three dispersivity values resulted in decreasing mean age with increasing dispersivity. This likely is a consequence of an edge effect. However, simulations for all three dispersivity values tested were mass balanced and stable demonstrating that the solution of the ground water age equation can provide estimates of water mass density distributions over age under real world conditions.

  19. Gene deletion and allelic replacement in the filamentous fungus Podospora anserina.

    PubMed

    El-Khoury, Riyad; Sellem, Carole H; Coppin, Evelyne; Boivin, Antoine; Maas, Marc F P M; Debuchy, Robert; Sainsard-Chanet, Annie

    2008-04-01

    Gene replacement via homologous recombination is a fundamental tool for the analysis of gene function. However, this event is rare in organisms like the filamentous fungus Podospora anserina. We show here that deletion of the PaKu70 gene is an efficient strategy for improving gene manipulation in this organism. By using the DeltaPaKu70 strain, it is now possible (1) to produce deletion mutants with an efficiency of 100%, (2) to achieve allelic exchange by introducing a mutated allele associated with a selection cassette at the locus, (3) to introduce a mutation in a gene without co-insertion of a selectable marker and without any modification of the target locus.

  20. 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...

  1. 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...

  2. Aging Research Using Mouse Models.

    PubMed

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

    2015-06-01

    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, and immune function, as well as 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.

  3. 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

  4. Genome-Wide Gene Expression Profiling of Fertilization Competent Mycelium in Opposite Mating Types in the Heterothallic Fungus Podospora anserina

    PubMed Central

    Coppin, Evelyne; Imbeaud, Sandrine; Grognet, Pierre; Delacroix, Hervé; Debuchy, Robert

    2011-01-01

    Background Mating-type loci in yeasts and ascomycotan filamentous fungi (Pezizomycotina) encode master transcriptional factors that play a critical role in sexual development. Genome-wide analyses of mating-type-specification circuits and mating-type target genes are available in Saccharomyces cerevisiae and Schizosaccharomyces pombe; however, no such analyses have been performed in heterothallic (self-incompatible) Pezizomycotina. The heterothallic fungus Podospora anserina serves as a model for understanding the basic features of mating-type control. Its mat+ and mat− mating types are determined by dissimilar allelic sequences. The mat− sequence contains three genes, designated FMR1, SMR1 and SMR2, while the mat+ sequence contains one gene, FPR1. FMR1 and FPR1 are the major regulators of fertilization, and this study presents a genome-wide view of their target genes and analyzes their target gene regulation. Methodology/Principal Findings The transcriptomic profiles of the mat+ and mat− strains revealed 157 differentially transcribed genes, and transcriptomic analysis of fmr1− and fpr1− mutant strains was used to determine the regulatory actions exerted by FMR1 and FPR1 on these differentially transcribed genes. All possible combinations of transcription repression and/or activation by FMR1 and/or FPR1 were observed. Furthermore, 10 additional mating-type target genes were identified that were up- or down-regulated to the same level in mat+ and mat− strains. Of the 167 genes identified, 32 genes were selected for deletion, which resulted in the identification of two genes essential for the sexual cycle. Interspecies comparisons of mating-type target genes revealed significant numbers of orthologous pairs, although transcriptional profiles were not conserved between species. Conclusions/Significance This study represents the first comprehensive genome-wide analysis of mating-type direct and indirect target genes in a heterothallic filamentous fungus

  5. Identification of a Hypothetical Protein from Podospora anserina as a Nitroalkane Oxidase

    SciTech Connect

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

    2010-08-23

    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{sub cat}/K{sub M}-pH profile with nitroethane shows a pK{sub a} of 5.9 that is assigned to Asp399 as the active site base. Mutation of Asp399 to asparagine decreases the k{sub cat}/K{sub 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 {angstrom}, confirming its identification as an NAO.

  6. Wood Utilization Is Dependent on Catalase Activities in the Filamentous Fungus Podospora anserina

    PubMed Central

    Bourdais, Anne; Bidard, Frederique; Zickler, Denise; Berteaux-Lecellier, Veronique; Silar, Philippe; Espagne, Eric

    2012-01-01

    Catalases are enzymes that play critical roles in protecting cells against the toxic effects of hydrogen peroxide. They are implicated in various physiological and pathological conditions but some of their functions remain unclear. In order to decipher the role(s) of catalases during the life cycle of Podospora anserina, we analyzed the role of the four monofunctional catalases and one bifunctional catalase-peroxidase genes present in its genome. The five genes were deleted and the phenotypes of each single and all multiple mutants were investigated. Intriguingly, although the genes are differently expressed during the life cycle, catalase activity is dispensable during both vegetative growth and sexual reproduction in laboratory conditions. Catalases are also not essential for cellulose or fatty acid assimilation. In contrast, they are strictly required for efficient utilization of more complex biomass like wood shavings by allowing growth in the presence of lignin. The secreted CATB and cytosolic CAT2 are the major catalases implicated in peroxide resistance, while CAT2 is the major player during complex biomass assimilation. Our results suggest that P. anserina produces external H2O2 to assimilate complex biomass and that catalases are necessary to protect the cells during this process. In addition, the phenotypes of strains lacking only one catalase gene suggest that a decrease of catalase activity improves the capacity of the fungus to degrade complex biomass. PMID:22558065

  7. Who Is Your Successful Aging Role Model?

    PubMed

    Jopp, Daniela S; Jung, Seojung; Damarin, Amanda K; Mirpuri, Sheena; Spini, Dario

    2017-03-01

    Having a role model of successful aging may contribute to views on aging. This article investigated the nature and correlates of young, middle-aged, and older adults' successful aging role models. One hundred and fifty-one individuals aged 18-99 were asked whether they had a role model of successful aging and if so, the reasons for their choice. Open-ended answers were coded for recurring themes. Views on aging and attitudes toward own aging were assessed with questionnaires. Eighty-five percent of participants indicated at least one role model. Most mentioned role models from their family, including parents and grandparents. Role models were gender matched. Most frequent reasons for model choices were health, activities, and social resources. Participants with family role models had less negative views on aging. Mediation analyses confirmed that family role models were associated with more reasons for role model choice, which in turn was associated with less negative views on aging. Furthermore, the effect of reasons on attitudes toward own aging was mediated by negative views on aging. Young, middle-aged, and older adults have role models for successful aging. Links between role model features and views on aging suggest that role models may be useful in promoting successful aging.

  8. A Network of HMG-box Transcription Factors Regulates Sexual Cycle in the Fungus Podospora anserina

    PubMed Central

    Ait Benkhali, Jinane; Coppin, Evelyne; Brun, Sylvain; Peraza-Reyes, Leonardo; Martin, Tom; Dixelius, Christina; Lazar, Noureddine; van Tilbeurgh, Herman; Debuchy, Robert

    2013-01-01

    High-mobility group (HMG) B proteins are eukaryotic DNA-binding proteins characterized by the HMG-box functional motif. These transcription factors play a pivotal role in global genomic functions and in the control of genes involved in specific developmental or metabolic pathways. The filamentous ascomycete Podospora anserina contains 12 HMG-box genes. Of these, four have been previously characterized; three are mating-type genes that control fertilization and development of the fruit-body, whereas the last one encodes a factor involved in mitochondrial DNA stability. Systematic deletion analysis of the eight remaining uncharacterized HMG-box genes indicated that none were essential for viability, but that seven were involved in the sexual cycle. Two HMG-box genes display striking features. PaHMG5, an ortholog of SpSte11 from Schizosaccharomyces pombe, is a pivotal activator of mating-type genes in P. anserina, whereas PaHMG9 is a repressor of several phenomena specific to the stationary phase, most notably hyphal anastomoses. Transcriptional analyses of HMG-box genes in HMG-box deletion strains indicated that PaHMG5 is at the hub of a network of several HMG-box factors that regulate mating-type genes and mating-type target genes. Genetic analyses revealed that this network also controls fertility genes that are not regulated by mating-type transcription factors. This study points to the critical role of HMG-box members in sexual reproduction in fungi, as 11 out of 12 members were involved in the sexual cycle in P. anserina. PaHMG5 and SpSte11 are conserved transcriptional regulators of mating-type genes, although P. anserina and S. pombe diverged 550 million years ago. Two HMG-box genes, SOX9 and its upstream regulator SRY, also play an important role in sex determination in mammals. The P. anserina and S. pombe mating-type genes and their upstream regulatory factor form a module of HMG-box genes analogous to the SRY/SOX9 module, revealing a commonality of sex

  9. [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.

  10. Cloning, sequencing, and transgenic expression of Podospora curvicolla and Sordaria macrospora eEF1A genes: relationship between cytosolic translation and longevity in filamentous fungi.

    PubMed

    Gagny, B; Rossignol, M; Silar, P

    1997-12-01

    We have cloned and sequenced the gene encoding the translation elongation factor eEF1A from two filamentous fungi, Podospora curvicolla and Sordaria macrospora. These fungi are close relatives of Podospora anserina and also show senescence syndromes. Comparison of the sequences of the deduced proteins with that of P. anserina reveals that the three proteins differ in several positions. Replacement of the P. anserina gene by either of the two exogenous genes does not entail any modification in P. anserina physiology; the longevity of the fungus is not affected. No alteration of in vivo translational accuracy was detected; however, the exogenous proteins nonetheless promoted a modification of the resistance to the aminoglycoside antibiotic paromomycin. These data suggest that optimization of life span between these closely related fungi has likely not been performed during evolution through modifications of eEF1A activity, despite the fact that mutations in this factor can drastically affect longevity. Copyright 1997 Academic Press.

  11. 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

  12. A concatenational graph evolution aging model.

    PubMed

    Suo, Jinli; Chen, Xilin; Shan, Shiguang; Gao, Wen; Dai, Qionghai

    2012-11-01

    Modeling the long-term face aging process is of great importance for face recognition and animation, but there is a lack of sufficient long-term face aging sequences for model learning. To address this problem, we propose a CONcatenational GRaph Evolution (CONGRE) aging model, which adopts decomposition strategy in both spatial and temporal aspects to learn long-term aging patterns from partially dense aging databases. In spatial aspect, we build a graphical face representation, in which a human face is decomposed into mutually interrelated subregions under anatomical guidance. In temporal aspect, the long-term evolution of the above graphical representation is then modeled by connecting sequential short-term patterns following the Markov property of aging process under smoothness constraints between neighboring short-term patterns and consistency constraints among subregions. The proposed model also considers the diversity of face aging by proposing probabilistic concatenation strategy between short-term patterns and applying scholastic sampling in aging prediction. In experiments, the aging prediction results generated by the learned aging models are evaluated both subjectively and objectively to validate the proposed model.

  13. 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…

  14. 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…

  15. Modelling the molecular mechanisms of aging

    PubMed Central

    Mc Auley, Mark T.; Guimera, Alvaro Martinez; Hodgson, David; Mcdonald, Neil; Mooney, Kathleen M.; Morgan, Amy E.

    2017-01-01

    The aging process is driven at the cellular level by random molecular damage that slowly accumulates with age. Although cells possess mechanisms to repair or remove damage, they are not 100% efficient and their efficiency declines with age. There are many molecular mechanisms involved and exogenous factors such as stress also contribute to the aging process. The complexity of the aging process has stimulated the use of computational modelling in order to increase our understanding of the system, test hypotheses and make testable predictions. As many different mechanisms are involved, a wide range of models have been developed. This paper gives an overview of the types of models that have been developed, the range of tools used, modelling standards and discusses many specific examples of models that have been grouped according to the main mechanisms that they address. We conclude by discussing the opportunities and challenges for future modelling in this field. PMID:28096317

  16. Modelling the molecular mechanisms of aging.

    PubMed

    Mc Auley, Mark T; Guimera, Alvaro Martinez; Hodgson, David; Mcdonald, Neil; Mooney, Kathleen M; Morgan, Amy E; Proctor, Carole J

    2017-02-28

    The aging process is driven at the cellular level by random molecular damage that slowly accumulates with age. Although cells possess mechanisms to repair or remove damage, they are not 100% efficient and their efficiency declines with age. There are many molecular mechanisms involved and exogenous factors such as stress also contribute to the aging process. The complexity of the aging process has stimulated the use of computational modelling in order to increase our understanding of the system, test hypotheses and make testable predictions. As many different mechanisms are involved, a wide range of models have been developed. This paper gives an overview of the types of models that have been developed, the range of tools used, modelling standards and discusses many specific examples of models that have been grouped according to the main mechanisms that they address. We conclude by discussing the opportunities and challenges for future modelling in this field.

  17. 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.

  18. 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.

  19. Mouse models and aging: longevity and progeria.

    PubMed

    Liao, Chen-Yu; Kennedy, Brian K

    2014-01-01

    Aging is a complex, multifactorial process that is likely influenced by the activities of a range of biological pathways. Genetic approaches to identify genes modulating longevity have been highly successful and recent efforts have extended these studies to mammalian aging. A variety of genetic models have been reported to have enhanced lifespan and, similarly, many genetic interventions lead to progeroid phenotypes. Here, we detail and evaluate both sets of models, focusing on the insights they provide about the molecular processes modulating aging and the extent to which mutations conferring progeroid pathologies really phenocopy accelerated aging.

  20. [Deafness and aging: studies in experimental models].

    PubMed

    Gil Loyzaga, Pablo E

    2002-01-01

    Since 1970 a progressive aging of the world population, mainly in the most developed countries, has been observed. Spain could have, around 2050, the most aged human population of the world. Therefore, scientist show an increasing interest on the study of the aging-related pathologies (i.e. deafness linked to aging process: presbycusis). The deep analysis of the presbycusis physiopathology will be based on the study of patients, but also on animal models. This report summarizes our results obtained on the analysis of the deafness linked to aging on the C57/BL/6 mice.

  1. The Penna Model of Biological Aging

    PubMed Central

    Stauffer, D.

    2007-01-01

    This review deals with computer simulation of biological aging, particularly with the Penna model of 1995. They are based on the mutation accumulation theory of half a century ago. The results agree well with demographical reality, and also with the seemingly contradictory influence of predators on the aging of prey. PMID:20066128

  2. 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.

  3. 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

  4. Two NADPH oxidase isoforms are required for sexual reproduction and ascospore germination in the filamentous fungus Podospora anserina.

    PubMed

    Malagnac, Fabienne; Lalucque, Hervé; Lepère, Gersende; Silar, Philippe

    2004-11-01

    NADPH oxidases are enzymes that produce reactive oxygen species (ROS) using electrons derived from intracellular NADPH. In plants and mammals, ROS have been proposed to be second messengers that signal defence responses or cell proliferation. By inactivating PaNox1 and PaNox2, two genes encoding NADPH oxidases, we demonstrate the crucial role of these enzymes in the control of two key steps of the filamentous fungus Podospora anserina life cycle. PaNox1 mutants are impaired in the differentiation of fruiting bodies from their progenitor cells, and the deletion of the PaNox2 gene specifically blocks ascospore germination. Furthermore, we show that PaNox1 likely acts upstream of PaASK1, a MAPKKK previously implicated in stationary phase differentiation and cell degeneration. Using nitro blue tetrazolium (NBT) and diaminobenzidine (DAB) assays, we detect a regulated secretion of both superoxide and peroxide during P. anserina vegetative growth. In addition, two oxidative bursts are shown to occur during fruiting body development and ascospore germination. Analysis of mutants establishes that PaNox1, PaNox2, and PaASK1, as well as a still unknown additional source of ROS, modulate these secretions. Altogether, our data point toward a role for NADPH oxidases in signalling fungal developmental transitions with respect to nutrient availability. These enzymes are conserved in other multicellular eukaryotes, suggesting that early eukaryotes were endowed with a redox network used for signalling purposes.

  5. Cultivation of Podospora anserina on soybean hulls results in an efficient enzyme cocktail for plant biomass hydrolysis.

    PubMed

    Mäkelä, Miia R; Bouzid, Ourdia; Robl, Diogo; Post, Harm; Peng, Mao; Heck, Albert; Altelaar, Maarten; de Vries, Ronald P

    2017-07-25

    The coprophilic ascomycete fungus Podospora anserina was cultivated on three different plant biomasses, i.e. cotton seed hulls (CSH), soybean hulls (SBH) and acid-pretreated wheat straw (WS) for four days, and the potential of the produced enzyme mixtures was compared in the enzymatic saccharification of the corresponding lignocellulose feedstocks. The enzyme cocktail P. anserina produced after three days of growth on SBH showed superior capacity to release reducing sugars from all tested plant biomass feedstocks compared to the enzyme mixtures from CSH and WS cultures. Detailed proteomics analysis of the culture supernatants revealed that SBH contained the most diverse set of enzymes targeted on plant cell wall polymers and was particularly abundant in xylan, mannan and pectin acting enzymes. The importance of lytic polysaccharide monooxygenases (LPMOs) in plant biomass deconstruction was supported by identification of 20 out of 33 AA9 LPMOs in the SBH cultures. The results highlight the suitability of P. anserina as a source of plant cell wall degrading enzymes for biotechnological applications and the importance of selecting the most optimal substrate for the production of enzyme mixtures. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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

  11. Aging with HIV: a model of disability.

    PubMed

    Solomon, Patricia; O'Brien, Kelly; Wilkins, Seanne; Gervais, Nicole

    2014-01-01

    The purpose of this qualitative study was to develop a theoretical model describing the disability experienced by older adults living with HIV. Forty nine HIV positive men and women over the age of 50 years participated in in-depth qualitative interviews. Transcribed interviews were analyzed using grounded theory techniques. Uncertainty or worrying about the future was at the core of the model. Components of disability including symptoms and impairments, difficulties with day to day activities and challenges to social participation were experienced in the context of extrinsic or environmental factors (social support, stigma) and intrinsic contextual factors (positive living strategies, age). Time was an overarching component of the model. The model suggests areas for interventions to prevent or reduce disability related to the consequences of aging with HIV and improve overall quality of life. © The Author(s) 2014.

  12. Animal and human models to understand ageing.

    PubMed

    Lees, Hayley; Walters, Hannah; Cox, Lynne S

    2016-11-01

    Human ageing is the gradual decline in organ and tissue function with increasing chronological time, leading eventually to loss of function and death. To study the processes involved over research-relevant timescales requires the use of accessible model systems that share significant similarities with humans. In this review, we assess the usefulness of various models, including unicellular yeasts, invertebrate worms and flies, mice and primates including humans, and highlight the benefits and possible drawbacks of each model system in its ability to illuminate human ageing mechanisms. We describe the strong evolutionary conservation of molecular pathways that govern cell responses to extracellular and intracellular signals and which are strongly implicated in ageing. Such pathways centre around insulin-like growth factor signalling and integration of stress and nutritional signals through mTOR kinase. The process of cellular senescence is evaluated as a possible underlying cause for many of the frailties and diseases of human ageing. Also considered is ageing arising from systemic changes that cannot be modelled in lower organisms and instead require studies either in small mammals or in primates. We also touch briefly on novel therapeutic options arising from a better understanding of the biology of ageing. Copyright © 2016. Published by Elsevier Ireland Ltd.

  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.

  14. Autophagy and aging: lessons from progeria models.

    PubMed

    Mariño, Guillermo; Fernández, Alvaro F; López-Otín, Carlos

    2010-01-01

    Autophagy is an evolutionarily conserved process essential for cellular homeostasis and organismal viability. In fact, this pathway is one of the major protein degradation mechanisms in eukaryotic cells. It has been repeatedly reported that the autophagic activity of living cells decreases with age, probably contributing to the accumulation of damaged macromolecules and organelles during aging. Moreover, autophagy modulation in different model organisms has yielded very promising results suggesting that the maintenance of a proper autophagic activity contributes to extend longevity. On the other hand, recent findings have shown that distinct premature-aging murine models exhibit an extensive basal activation of autophagy instead of the characteristic decline in this process occurring during normal aging. This unexpected autophagic increase in progeroid models is usually associated with a series of metabolic alterations resembling those occurring under calorie restriction or in other situations reported to prolong life-span. In this chapter, we will discuss the current knowledge on the relationship between the autophagy pathway and aging with a special emphasis on the unexpected and novel link between premature aging and autophagy up-regulation.

  15. 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.

  16. [Cognitive neuroscience of aging: explanatory models].

    PubMed

    Grandi, Fabrissio; Tirapu Ustárroz, Javier

    2017-05-12

    The aim of the cognitive neuroscience of aging is the study of brain activity and the cognitive processes associated with age. In order to understand the dynamics of neurocognitive activity in older people, the present review highlights four explanatory models. The first one (HAROLD) highlights brain bilaterality, mainly in the pre-frontal cortex. The second paradigm (PASA) places special emphasis on neuronal polarisation (anterior-posterior). The third model (CRUNCH) relates the manifest activity of the brain to the level of complexity of the task. The last one (ELSA) emphasises the spatial and temporal distribution of brain activity in the different phases of recovery. Although different in their content, the four explanatory models are perfectly compatible with the findings reported by neuroimaging techniques, suggesting the use of compensation strategies and cognitive reserve for interventions that may help to optimise the performance of older people. Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. 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

  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. Animal models of age related macular degeneration.

    PubMed

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

    2012-08-01

    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.

  20. 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

  1. Computational modeling of material aging effects

    SciTech Connect

    Fang, H.E.

    1996-07-01

    Progress is being made in our efforts to develop computational models for predicting material property changes in weapon components due to aging. The first version of a two-dimensional lattice code for modeling thermomechanical fatigue, such as has been observed in solder joints on electronic components removed from the stockpile, has been written and tested. The code does a good qualitative job of presenting intergranular and/or transgranular cracking in a polycrystalline material when under thermomechanical deformation. The current progress is an encouraging start for our long term effort to develop multi-level simulation capabilities, with the technology of high performance computing, for predicting age-related effects on the reliability of weapons.

  2. Aging, Breast Cancer and the Mouse Model

    DTIC Science & Technology

    2005-05-01

    Presenescent or senescent hBF (1.2 or 18x×10 4/well, respectively) [M, Stampfer , P. Yaswen, Lawrence Berkeley National Laboratory wdre suspended in 60 l cold...2.8 1 2.8 Inducing a human-like senescent phenotype in mouse fibroblasts Jean-Philihoo Copp , Simona Parrinello, Ana Krtolica, Christopher K. Patil...MAMMARY EPITHELIAL CELL PROLIFERATION AND TUMORIGENESIS: A MOUSE MODEL FOR HUMAN AGING. Jean-Philippe Coppe, Simona Parrinello, Ana Krtolica, Christopher

  3. Micromechanical Modeling of Concrete at Early Age

    NASA Astrophysics Data System (ADS)

    Tuleubekov, Kairat

    The focus of this research is a micromechanical characterization of Portland cement concrete at early age (less than 28 days). Concrete's viscoelastic properties change significantly at early age due to solidification of its matrix component. Bazant's solidification theory models concrete as a material solidifying in time. This approach is generalized to a three-dimensional characterization of a composite material with a solidifying matrix and elastic inclusions. An integral constitutive relationship was obtained using a generalized correspondence principle and homogenization techniques for elastic composite materials. In light of this approach, effective creep properties of composite spherical assemblage with an aging matrix are obtained. In addition, the elastic Hashin-Monteiro model is generalized to account for the effect of the interfacial transition zone properties on concrete creep. An effective computational platform was developed to evaluate operator expressions in order to obtain relaxation and creep functions numerically. Through numerical examples, it is shown that triaxial generalization of Bazant's solidification model enables robust and computationally efficient prediction of creep deformations in Portland cement concrete.

  4. Speciation Effect in the Penna Aging Model

    NASA Astrophysics Data System (ADS)

    Łaszkiewicz, A.; Szymczak, Sz.; Cebrat, S.

    We have simulated the evolution of diploid, sexually reproducing populations using the Penna model of aging. We have noted that diminishing the recombination frequency during the gamete production generates a specific diversity of genomes in the populations. When two populations independently evolving for some time were mixed in one environmental niche of the limited size and crossbreeding between them was allowed, the average lifespan of hybrids was significantly shorter than the lifespan of the individuals of parental lines. Another effect of higher hybrid mortality is the faster elimination of one parental line from the shared environment. The two populations living in one environment co-exist much longer if they are genetically separated — they compete as two species instead of crossbreeding. This effect can be considered as the first step to speciation — any barrier eliminating crossbreeding between these populations, leading to speciation, would favor the populations.

  5. 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…

  6. 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…

  7. 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

  8. 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.

  9. Evolutionary model with genetics, aging, and knowledge.

    PubMed

    Bustillos, Armando Ticona; de Oliveira, Paulo Murilo C

    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.

  10. 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.

  11. Biological implications of the Weibull and Gompertz models of aging.

    PubMed

    Ricklefs, Robert E; Scheuerlein, Alex

    2002-02-01

    Gompertz and Weibull functions imply contrasting biological causes of demographic aging. The terms describing increasing mortality with age are multiplicative and additive, respectively, which could result from an increase in the vulnerability of individuals to extrinsic causes in the Gompertz model and the predominance of intrinsic causes at older ages in the Weibull model. Experiments that manipulate extrinsic mortality can distinguish these biological models. To facilitate analyses of experimental data, we defined a single index for the rate of aging (omega) for the Weibull and Gompertz functions. Each function described the increase in aging-related mortality in simulated ages at death reasonably well. However, in contrast to the Weibull omega(W), the Gompertz omega(G) was sensitive to variation in the initial mortality rate independently of aging-related mortality. Comparisons between wild and captive populations appear to support the intrinsic-causes model for birds, but give mixed support for both models in mammals.

  12. Age-Of Dependent Mutation Rate and Weak Children in the Penna Model in Biological Ageing

    NASA Astrophysics Data System (ADS)

    Berntsen, K. Nikolaj

    We investigate the effect of an age-dependent mutation rate in the Penna model of ageing and then we observe that the high mortality for human babies can be reproduced by the model if one assumes babies to be weaker than adults.

  13. Modeling Creep Processes in Aging Polymers

    NASA Astrophysics Data System (ADS)

    Olali, N. V.; Voitovich, L. V.; Zazimko, N. N.; Malezhik, M. P.

    2016-03-01

    The photoelastic method is generalized to creep in hereditary aging materials. Optical-creep curves and mechanical-creep or optical-relaxation curves are used to interpret fringe patterns. For materials with constant Poisson's ratio, it is sufficient to use mechanical- or optical-creep curves for this purpose

  14. Computer Modelling of Age Hardening for Isothermally Aged Al-Mg-Si Alloys

    NASA Astrophysics Data System (ADS)

    Wu, Linda; Ferguson, W. George

    Computer modelling, due to it saving time and money, has been widely used in industrial simulation. The present model, which is based on the Shercliff-Ashby methodology for the ageing of aluminum alloys, can be used to predict the yield strength (or hardness) of Al-Mg-Si alloys for the artificial ageing temperature below the solvus temperature as a function of time. With suitable input data, this model can be applied to most Al-Mg-Si alloys, wrought or cast. In the present model, input data for aluminium alloys of A356, A357 and 6061 is taken from the open literature, and then the unknown constants are calibrated from these data. After calibration, the ageing curves are constructed for different isothermal ageing temperatures. Finally, experimentally ageing heat treatments at different temperatures for casting alloys of A356 were done to validate the model.

  15. [Active ageing and success: A brief history of conceptual models].

    PubMed

    Petretto, Donatella Rita; Pili, Roberto; Gaviano, Luca; Matos López, Cristina; Zuddas, Carlo

    2016-01-01

    The aim of this paper is to analyse and describe different conceptual models of successful ageing, active and healthy ageing developed in Europe and in America in the 20° century, starting from Rowe and Kahn's original model (1987, 1997). A narrative review was conducted on the literature on successful ageing. Our review included definition of successful ageing from European and American scholars. Models were found that aimed to describe indexes of active and healthy ageing, models devoted to describe processes involved in successful ageing, and additional views that emphasise subjective and objective perception of successful ageing. A description is also given of critiques on previous models and remedies according to Martin et al. (2014) and strategies for successful ageing according to Jeste and Depp (2014). The need is discussed for the enhancement of Rowe and Kahn's model and other models with a more inclusive, universal description of ageing, incorporating scientific evidence regarding active ageing. Copyright © 2015 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. Multivariate Longitudinal Modeling of Cognitive Aging

    PubMed Central

    Robitaille, Annie; Muniz, Graciela; Piccinin, Andrea M.; Johansson, Boo; Hofer, Scott M.

    2013-01-01

    We illustrate the use of the parallel latent growth curve model using data from OCTO-Twin. We found a significant intercept-intercept and slope-slope association between processing speed and visuospatial ability. Within-person correlations among the occasion-specific residuals were significant, suggesting that the occasion-specific fluctuations around individual’s trajectories, after controlling for intraindividual change, are related between both outcomes. Random and fixed effects for visuospatial ability are reduced when we include structural parameters (directional growth curve model) providing information about changes in visuospatial abilities after controlling for processing speed. We recommend this model to researchers interested in the analysis of multivariate longitudinal change, as it permits decomposition and directly interpretable estimates of association among initial levels, rates of change, and occasion-specific variation. PMID:23589712

  3. 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…

  4. [Study on establishment of kidney deficient aging model and comparison with D-galactose induced aging model].

    PubMed

    Li, Zhan; Liu, Renhui; Kang, Xue; Wang, Xiujuan

    2012-08-01

    To establish a kidney deficient aging model (KDAM), assess it in antioxidant capacity, HPAT axis function and bone metabolism, and compare with D-galactose aging model. Aging rat model was established by injecting D-galactose solution, meanwhile dexamethasone solution was injected to establish kidney deficient aging model. Then these models were evaluated by serum MDA (malondialdehyde) and GSH-Px (glutathione peroxidase), liver SOD (superoxide dismutase), adrenal, thymus and spleen index, CD4(+), CD8(+), and serum COR (cortisol), BGP (bone Gla-protein), plasma ACTH (adrenocorticotropic hormone) and CRH (corticotropin-releasing hormone). Compared with the normal group, the aging model group and the kidney deficient aging group showed significant decrease in liver SOD activity (P < 0.01 on average) and significant increase in serum MDA content (P < 0.01 on average) , and the kidney deficient aging group revealed remarkable decline in plasma ACTH content (P < 0.05). Compared with the normal group and the aging model group, the kidney deficient aging model group's weight, serum GSH-Px decreased (P < 0.01, P < 0.05), adrenal index decreased (P < 0.05, P < 0.01), serum COR decreased (P < 0.05 on average), plasma CRH increased (P < 0.05, P < 0.01), serum BGP content significantly decreased (P < 0.01 on average), value of CD4(+), CD8(+) decreased (P < 0.05, P < 0.01), CD4(+)/CD8(+) increased, but without significant difference. The kidney deficient aging model shows significant decrease in antioxidant capacity, dysfunction of HPAT axis disorder and abnormal bone metabolism. However, D-galactose aging model only shows a significant difference in antioxidant capacity.

  5. Global Protein Oxidation Profiling Suggests Efficient Mitochondrial Proteome Homeostasis During Aging*

    PubMed Central

    Ramallo Guevara, Carina; Philipp, Oliver; Hamann, Andrea; Werner, Alexandra; Osiewacz, Heinz D.; Rexroth, Sascha; Rögner, Matthias; Poetsch, Ansgar

    2016-01-01

    The free radical theory of aging is based on the idea that reactive oxygen species (ROS) may lead to the accumulation of age-related protein oxidation. Because themajority of cellular ROS is generated at the respiratory electron transport chain, this study focuses on the mitochondrial proteome of the aging model Podospora anserina as target for ROS-induced damage. To ensure the detection of even low abundant modified peptides, separation by long gradient nLC-ESI-MS/MS and an appropriate statistical workflow for iTRAQ quantification was developed. Artificial protein oxidation was minimized by establishing gel-free sample preparation in the presence of reducing and iron-chelating agents. This first large scale, oxidative modification-centric study for P. anserina allowed the comprehensive quantification of 22 different oxidative amino acid modifications, and notably the quantitative comparison of oxidized and nonoxidized protein species. In total 2341 proteins were quantified. For 746 both protein species (unmodified and oxidatively modified) were detected and the modification sites determined. The data revealed that methionine residues are preferably oxidized. Further prominent identified modifications in decreasing order of occurrence were carbonylation as well as formation of N-formylkynurenine and pyrrolidinone. Interestingly, for the majority of proteins a positive correlation of changes in protein amount and oxidative damage were noticed, and a general decrease in protein amounts at late age. However, it was discovered that few proteins changed in oxidative damage in accordance with former reports. Our data suggest that P. anserina is efficiently capable to counteract ROS-induced protein damage during aging as long as protein de novo synthesis is functioning, ultimately leading to an overall constant relationship between damaged and undamaged protein species. These findings contradict a massive increase in protein oxidation during aging and rather suggest a

  6. 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.

  7. 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].

  8. 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.

  9. 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.

  10. Cerebrovascular hemodynamic correlates of aging in the Lou/c rat: a model of healthy aging.

    PubMed

    Dubeau, S; Ferland, G; Gaudreau, P; Beaumont, E; Lesage, F

    2011-06-15

    The LOU/c rat is an inbred strain considered a model of healthy aging. It exhibits a longer free disease lifespan and a low adiposity throughout life. While this animal model has been shown to maintain eating behavior and neuroendocrine, metabolic and cognitive functions with age, no study has yet investigated vascular correlates in this model of healthy aging. In the present work, multispectral optical imaging was used to investigate the hemodynamic response in the somatosensory cortex of LOU/c rats following forepaw stimulation in three age groups, 4, 24 and 40months. Results indicate reduced hemodynamic responses in the contralateral somatosensory cortex between young (4months) and older groups following stimulation. This decrease was associated with an increase in the spatial extent of activation. The ipsilateral response did not change with aging leading to decreased laterality. Estimations of the relative change in the local cerebral metabolic rate of oxygen during stimulation based on multimodal data showed no significant change with age. The exponent describing the relation between blood volume and blood flow changes, Grubb's parameter, did display a significant change with age which may suggest vessel compliance modifications. This work finds its relevance in recent findings underlying the importance of vascular changes with aging and its impact on neurodegenerative disease.

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

    NASA Astrophysics Data System (ADS)

    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 [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

  12. 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.

  13. Aging mechanism in model Pickering emulsion

    NASA Astrophysics Data System (ADS)

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

    We study the stability of a model Pickering emulsion system. A special counter-flow microfluidics set-up was used to prepare monodisperse Pickering emulsions, with 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 microfluidics setup. A surface coverage as low as 23$\\%$ is enough to stabilize the emulsions and we evidence a new regime of Pickering emulsion stability where the surface coverage of emulsion droplets of constant size increases in time, in coexistence with a large amount of dispersed 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.

  14. Exploring the power of yeast to model aging and age-related neurodegenerative disorders.

    PubMed

    Oliveira, Ana V; Vilaça, Rita; Santos, Cláudia N; Costa, Vítor; Menezes, Regina

    2017-02-01

    Aging is a multifactorial process determined by molecular, cellular and systemic factors and it is well established that advancing age is a leading risk factor for several neurodegenerative diseases. In fact, the close association of aging and neurodegenerative disorders has placed aging as the greatest social and economic challenge of the 21st century, and age-related diseases have also become a key priority for countries worldwide. The growing need to better understand both aging and neurodegenerative processes has led to the development of simple eukaryotic models amenable for mechanistic studies. Saccharomyces cerevisiae has proven to be an unprecedented experimental model to study the fundamental aspects of aging and to decipher the intricacies of neurodegenerative disorders greatly because the molecular mechanisms underlying these processes are evolutionarily conserved from yeast to human. Moreover, yeast offers several methodological advantages allowing a rapid and relatively easy way of establishing gene-protein-function associations. Here we review different aging theories, common cellular pathways driving aging and neurodegenerative diseases and discuss the major contributions of yeast to the state-of-art knowledge in both research fields.

  15. 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)

  16. Shared Ageing Research Models (ShARM): a new facility to support ageing research.

    PubMed

    Duran, Adele L; Potter, Paul; Wells, Sara; Kirkwood, Tom; von Zglinicki, Thomas; McArdle, Anne; Scudamore, Cheryl; Meng, Qing-Jun; de Haan, Gerald; Corcoran, Anne; Bellantuono, Ilaria

    2013-12-01

    In order to manage the rise in life expectancy and the concomitant increased occurrence of age-related diseases, research into ageing has become a strategic priority. Mouse models are commonly utilised as they share high homology with humans and show many similar signs and diseases of ageing. However, the time and cost needed to rear aged cohorts can limit research opportunities. Sharing of resources can provide an ethically and economically superior framework to overcome some of these issues but requires dedicated infrastructure. Shared Ageing Research Models (ShARM) ( www.ShARMUK.org ) is a new, not-for-profit organisation funded by Wellcome Trust, open to all investigators. It collects, stores and distributes flash frozen tissues from aged murine models through its biorepository and provides a database of live ageing mouse colonies available in the UK and abroad. It also has an online environment (MICEspace) for collation and analysis of data from communal models and discussion boards on subjects such as the welfare of ageing animals and common endpoints for intervention studies. Since launching in July 2012, thanks to the generosity of researchers in UK and Europe, ShARM has collected more than 2,500 tissues and has in excess of 2,000 mice registered in live ageing colonies. By providing the appropriate support, ShARM has been able to bring together the knowledge and experience of investigators in the UK and Europe to maximise research outputs with little additional cost and minimising animal use in order to facilitate progress in ageing research.

  17. 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

  18. Housekeeping Genes and Death Genes in the Penna Aging Model

    NASA Astrophysics Data System (ADS)

    Niewczas, E.; Kurdziel, A.; Cebrat, S.

    The Penna model of aging predicts the accumulation of defective genes expressed after the organism reaches the minimum reproduction age in the genetic pool of the population. The accumulation of defects in the genomes implicates the specific age structure of the modeled populations. Nevertheless, the fraction of defective alleles at loci switched on before the reproduction period does not depend on exact age when precisely they are switched on, it may be just after conception or after birth. We have modeled the mortality of a population in the period before the minimum reproduction age, even before birth, assuming that sets of genes of different size are switched on in different periods of the life span.

  19. 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.

  20. 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.

  1. The role of forest age in earth system models

    NASA Astrophysics Data System (ADS)

    Poulter, B.; Bellassen, V.; Lin, X.; Luyssaert, S.; Nachin, B.; Pederson, N.; Shchepashchenko, D.; Shvidenko, A.; Ciais, P.

    2012-12-01

    The age of a forest has a principal role in determining the magnitude of carbon stocks and fluxes. As forests grow older, carbon tends to accumulate in above and belowground biomass causing changes in forest canopy complexity, nutrient pools, and the balance between carbon uptake and release. While age is a standard variable for forestry models, the present generation of earth system models neglects a representation of forest age for several reasons. These include the challenge in representing sub-grid cell ecosystem heterogeneity, a poor understanding of how ecosystem processes evolve with age, and because of a lack of forest age data with which to initialize models. Here we present a globally gridded forest age distribution dataset that is derived from National Forest Inventory data and from satellite-derived disturbance frequencies. This gridded dataset is developed at 0.5° spatial resolution at the plant functional types classification level, one that is commonly used in dynamic global vegetation models. We find large national-scale differences in forest age distributions, for example, with a peak age-area for young forests in China, and more mature forests across Canada and in Russia. Comparing simulated forest carbon stocks and fluxes from three DGVM models (LPJ, ORCHIDEE, and ORCHIDEE-Forest Management) with a global forest database, we illustrate the importance of accounting for structural development as forests develop. With over half the world's forests modified by human activities, or influenced by natural disturbance, spatial patterns of forest age distributions are a necessary feature of forward models for closing the global carbon budget within a consistent modeling framework.

  2. 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.

  3. Travelling Wave Solutions in Multigroup Age-Structured Epidemic Models

    NASA Astrophysics Data System (ADS)

    Ducrot, Arnaut; Magal, Pierre; Ruan, Shigui

    2010-01-01

    Age-structured epidemic models have been used to describe either the age of individuals or the age of infection of certain diseases and to determine how these characteristics affect the outcomes and consequences of epidemiological processes. Most results on age-structured epidemic models focus on the existence, uniqueness, and convergence to disease equilibria of solutions. In this paper we investigate the existence of travelling wave solutions in a deterministic age-structured model describing the circulation of a disease within a population of multigroups. Individuals of each group are able to move with a random walk which is modelled by the classical Fickian diffusion and are classified into two subclasses, susceptible and infective. A susceptible individual in a given group can be crisscross infected by direct contact with infective individuals of possibly any group. This process of transmission can depend upon the age of the disease of infected individuals. The goal of this paper is to provide sufficient conditions that ensure the existence of travelling wave solutions for the age-structured epidemic model. The case of two population groups is numerically investigated which applies to the crisscross transmission of feline immunodeficiency virus (FIV) and some sexual transmission diseases.

  4. Mouse models of age-related mitochondrial neurosensory hearing loss.

    PubMed

    Han, Chul; Someya, Shinichi

    2013-07-01

    Hearing loss is the most common sensory disorder in the elderly population. Overall, 10% of the population has a hearing loss in the US, and this age-related hearing disorder is projected to afflict more than 28 million Americans by 2030. Age-related hearing loss is associated with loss of sensory hair cells (sensory hearing loss) and/or spiral ganglion neurons (neuronal hearing loss) in the cochlea of the inner ear. Many lines of evidence indicate that oxidative stress and associated mitochondrial dysfunction play a central role in age-related neurodegenerative diseases and are a cause of age-related neurosensory hearing loss. Yet, the molecular mechanisms of how oxidative stress and/or mitochondrial dysfunction lead to hearing loss during aging remain unclear, and currently there is no treatment for this age-dependent disorder. Several mouse models of aging and age-related diseases have been linked to age-related mitochondrial neurosensory hearing loss. Evaluation of these animal models has offered basic knowledge of the mechanism underlying hearing loss associated with oxidative stress, mitochondrial dysfunction, and aging. Here we review the evidence that specific mutations in the mitochondrial DNA or nuclear DNA that affect mitochondrial function result in increased oxidative damage and associated loss of sensory hair cells and/or spiral ganglion neurons in the cochlea during aging, thereby causing hearing loss in these mouse models. Future studies comparing these models will provide further insight into fundamental knowledge about the disordered process of hearing and treatments to improve the lives of individuals with communication disorders. This article is part of a Special Issue entitled 'Mitochondrial function and dysfunction in neurodegeneration'. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Models of the Aging Brain Structure and Individual Decline

    PubMed Central

    Ziegler, Gabriel; Dahnke, Robert; Gaser, Christian

    2012-01-01

    The aging brain’s structural development constitutes a spatiotemporal process that is accessible by MR-based computational morphometry. Here we introduce basic concepts and analytical approaches to quantify age-related differences and changes in neuroanatomical images of the human brain. The presented models first address the estimation of age trajectories, then we consider inter-individual variations of structural decline, using a repeated measures design. We concentrate our overview on preprocessed neuroanatomical images of the human brain to facilitate practical applications to diverse voxel- and surface-based structural markers. Together these methods afford analysis of aging brain structure in relation to behavioral, health, or cognitive parameters. PMID:22435060

  6. 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.

  7. Exact solution of an evolutionary model without aging.

    PubMed

    Onody, R N; de Medeiros, N G

    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.

  8. 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.

  9. Effect Of Oceanic Lithosphere Age Errors On Model Discrimination

    NASA Astrophysics Data System (ADS)

    DeLaughter, J. E.

    2016-12-01

    The thermal structure of the oceanic lithosphere is the subject of a long-standing controversy. Because the thermal structure varies with age, it governs properties such as heat flow, density, and bathymetry with important implications for plate tectonics. Though bathymetry, geoid, and heat flow for young (<70 MY) lithosphere fit a half space model which varies as the inverse square of age, it appears to be shallower than expected for older lithosphere indicating a plate model is a better fit. It is therefore useful to jointly fit bathymetry, geoid, and heat flow data to an inverse model to determine lithospheric structure details. Though inverse models usually include the effect of errors in bathymetry, heat flow, and geoid, they rarely examine the effects of errors in age. This may have the effect of introducing subtle biases into inverse models of the oceanic lithosphere. Because the inverse problem for thermal structure is both ill-posed and ill-conditioned, these overlooked errors may have a greater effect than expected. The problem is further complicated by the non-uniform distribution of age and errors in age estimates; for example, only 30% of the oceanic lithosphere is older than 80 MY and less than 3% is older than 150 MY. To determine the potential strength of such biases, I have used the age and error maps of Mueller et al (2008) to forward model the bathymetry for half space and GDH1 plate models. For ages less than 20 MY, both models give similar results. The errors induced by uncertainty in age are relatively large and suggest that when possible young lithosphere should be excluded when examining the lithospheric thermal model. As expected, GDH1 bathymetry converges asymptotically on the theoretical result for error-free data for older data. The resulting uncertainty is nearly as large as that introduced by errors in the other parameters; in the absence of other errors, the models can only be distinguished for ages greater than 80 MY. These results

  10. The Healthy Aging Research Network: Modeling Collaboration for Community Impact.

    PubMed

    Belza, Basia; Altpeter, Mary; Smith, Matthew Lee; Ory, Marcia G

    2017-03-01

    As the first Centers for Disease Control and Prevention (CDC) Prevention Research Centers Program thematic network, the Healthy Aging Research Network was established to better understand the determinants of healthy aging within older adult populations, identify interventions that promote healthy aging, and assist in translating research into sustainable community-based programs throughout the nation. To achieve these goals requires concerted efforts of a collaborative network of academic, community, and public health organizational partnerships. For the 2001-2014 Prevention Research Center funding cycles, the Healthy Aging Research Network conducted prevention research and promoted the wide use of practices known to foster optimal health. Organized around components necessary for successful collaborations (i.e., governance and infrastructure, shaping focus, community involvement, and evaluation and improvement), this commentary highlights exemplars that demonstrate the Healthy Aging Research Network's unique contributions to the field. The Healthy Aging Research Network's collaboration provided a means to collectively build capacity for practice and policy, reduce fragmentation and duplication in health promotion and aging research efforts, maximize the efficient use of existing resources and generate additional resources, and ultimately, create synergies for advancing the healthy aging agenda. This collaborative model was built upon a backbone organization (coordinating center); setting of common agendas and mutually reinforcing activities; and continuous communications. Given its successes, the Healthy Aging Research Network model could be used to create new and evaluate existing thematic networks to guide the translation of research into policy and practice.

  11. The development of small primate models for aging research.

    PubMed

    Fischer, Kathleen E; Austad, Steven N

    2011-01-01

    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.

  12. 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

  13. Age-related bone loss in the LOU/c rat model of healthy ageing.

    PubMed

    Duque, Gustavo; Rivas, Daniel; Li, Wei; Li, Ailian; Henderson, Janet E; Ferland, Guylaine; Gaudreau, Pierrette

    2009-03-01

    Inbred albino Louvain (LOU) rats are considered a model of healthy aging due to their increased longevity in the absence of obesity and with a low incidence of common age-related diseases. In this study, we characterized the bone phenotype of male and female LOU rats at 4, 20 and 27 months of age using quantitative micro computed tomographic (mCT) imaging, histology and biochemical analysis of circulating bone biomarkers. Bone quality and morphometry of the distal femora, assessed by mCT, was similar in male and female rats at 4 months of age and deteriorated over time. Histochemical staining of undecalcified bone showed a significant reduction in cortical and trabecular bone by 20 months of age. The reduction in mineralized tissue was accompanied by reduced numbers of osteoblasts and osteoclasts and a significant increase in marrow adiposity. Biochemical markers of bone turnover, C-telopeptide and osteocalcin, correlated with the age-related bone loss whereas the calciotropic hormones PTH and vitamin D remained unchanged over time. In summary, aged LOU rats exhibit low-turnover bone loss and marrow fat infiltration, which are the hallmarks of senile osteoporosis, and thus represent a novel model in which to study the molecular mechanisms leading to this disorder.

  14. 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

  15. 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.

  16. 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

  17. Age and equity in liver transplantation: An organ allocation model.

    PubMed

    Cucchetti, Alessandro; Ross, Lainie Friedman; Thistlethwaite, J Richard; Vitale, Alessandro; Ravaioli, Matteo; Cescon, Matteo; Ercolani, Giorgio; Burra, Patrizia; Cillo, Umberto; Pinna, Antonio Daniele

    2015-10-01

    A moral liver allocation policy must be fair. We considered a 2-step, 2-principle allocation system called "age mapping." Its first principle, equal opportunity, ensures that candidates of all ages have an equal chance of getting an organ. Its second principle, prudential lifespan equity, allocates younger donor grafts to younger candidates and older donors to older candidates in order to increase the likelihood that all recipients achieve a "full lifespan." Data from 2476 candidates and 1371 consecutive adult liver transplantations (from 1999 to 2012) were used to determine whether age mapping can reduce the gap in years of life lost (YLL) between younger and older recipients. A parametric Weibull prognostic model was developed to estimate total life expectancy after transplantation using survival of the general population matched by sex and age as a reference. Life expectancy from birth was calculated by adding age at transplant and total life expectancy after transplantation. In multivariate analysis, recipient age, hepatitis C virus status, Model for End-Stage Liver Disease score at transplant of >30, and donor age were significantly related to prognosis after surgery (P < 0.05). The mean (and standard deviation) number of years of life from birth, calculated from the current allocation model, for various age groups were: recipients 18-47 years (n = 340) = 65.2 (3.3); 48-55 years (n = 387) = 72.7 (2.1); 56-61 years (n = 372) = 74.7 (1.7) and for recipients >61 years (n = 272) = 77.4 (1.4). The total number of YLL equaled 523 years. Redistributing liver grafts, using an age mapping algorithm, reduces the lifespan gap between younger and older candidates by 33% (from 12.3% to 8.3%) and achieves a 14% overall reduction of YLL (73 years) compared to baseline liver distribution. In conclusion, deliberately incorporating age into an allocation algorithm promotes fairness and increases efficiency.

  18. AFISMIP: Age Field in Ice Sheet Modeling Intercomparison Project

    NASA Astrophysics Data System (ADS)

    Parrenin, F.

    2009-04-01

    The last few years have seen a great deal of effort invested by various research groups in developing numerical ice sheet models. One interest of these models is to evaluate the age field of current or past ice sheets. Indeed, such a modeling exercise can be used to prospect for new drilling sites aiming at retrieving very old ice (e.g. >1 Myr). Reciprocally, observations on the age field provided by (1) already drilled ice cores or (2) internal layers measured by radio-echo sounding, can constrain the velocity field in ice sheet. The purpose of the proposed experiments is to address the accuracy of the numerical models of the age field. Numerical simulations will be inter-compared or confronted to analytical solutions.

  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. Copyright © 2016 Elsevier Ireland Ltd. All

  20. 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

  1. "Oxygen supply" as modulator of aging processes: hypoxia and hyperoxia models for aging studies.

    PubMed

    Cataldi, Amelia; Di Giulio, Camillo

    2009-07-01

    Cell growth is regulated by several factors, including oxygen supply, which influence cell metabolism. Aging is characterized by decreased oxygen supply to tissue, a reduction of tissue PO(2) and of the activity of several enzymes and metabolic factors. The oxygen-gradient diffusion at capillary tissue level is essential for the cellular survival, while the homeostasis of the oxygen in the arterial blood is mediated by reflexes sensitive to oxygen decrease and by release of several factors. Aging is correlated with a reduction of cells' oxygen supply concomitant to a parallel decrease in oxygen demand by tissues. Both chronic hypoxia or hyperoxia are considered as stresses. Indeed, in both conditions, free radical species, which damage structural and functional components of the membrane, are generated. ROS (reactive oxygen species) are physiological products of aerobic life and their accumulation affects aging. Because hypoxia per se modulates mitochondria activity, influencing oxygen consumption, hypoxia and aging could share some link. Moreover, the observation that in hypoxia or hyperoxia there is an accumulation of lipofucsine as a general reaction to stress is consistent with the accumulation of such components during aging. Correlation between hypoxia-hyperoxia and life-span remains open until we solve the question of how and why do cells sense oxygen. In other words, to better understand aging we need to know what O(2) species are being sensed by cells. In conclusion, hypoxia and hyperoxia represent an experimental model adequate for studying aging processes.

  2. 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.

  3. Lattice Modeling of Early-Age Behavior of Structural Concrete

    PubMed Central

    Pan, Yaming; Prado, Armando; Porras, Rocío; Hafez, Omar M.; Bolander, John E.

    2017-01-01

    The susceptibility of structural concrete to early-age cracking depends on material composition, methods of processing, structural boundary conditions, and a variety of environmental factors. Computational modeling offers a means for identifying primary factors and strategies for reducing cracking potential. Herein, lattice models are shown to be adept at simulating the thermal-hygral-mechanical phenomena that influence early-age cracking. In particular, this paper presents a lattice-based approach that utilizes a model of cementitious materials hydration to control the development of concrete properties, including stiffness, strength, and creep resistance. The approach is validated and used to simulate early-age cracking in concrete bridge decks. Structural configuration plays a key role in determining the magnitude and distribution of stresses caused by volume instabilities of the concrete material. Under restrained conditions, both thermal and hygral effects are found to be primary contributors to cracking potential. PMID:28772590

  4. 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.

  5. 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.

  6. 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

  7. Tuberculosis in Cape Town: an age-structured transmission model

    PubMed Central

    Blaser, Nello; Zahnd, Cindy; Hermans, Sabine; Salazar-Vizcaya, Luisa; Estill, Janne; Morrow, Carl; Egger, Matthias; Keiser, Olivia; Wood, Robin

    2015-01-01

    Background Tuberculosis (TB) is the leading cause of death in South Africa. The burden of disease varies by age, with peaks in TB notification rates in the HIV-negative population at ages 0-5, 20-24 and 45-49 years. There is little variation between age groups in the rates in the HIV-positive population. The drivers of this age pattern remain unknown. Methods We developed an age-structured simulation model of Mycobacterium tuberculosis (Mtb) transmission in Cape Town, South Africa. We considered five states of TB progression: susceptible, infected (latent TB), active TB, treated TB and treatment default. Latently infected individuals could be re-infected; a previous Mtb infection slowed progression to active disease. We further considered three states of HIV progression: HIV negative, HIV positive, on antiretroviral therapy. To parameterize the model, we analysed treatment outcomes from the Cape Town electronic TB register, social mixing patterns from a Cape Town community and literature estimates for other parameters. To investigate the main drivers behind the age patterns, we conducted sensitivity analyses on all parameters related to the age structure. Results The model replicated the age patterns in HIV-negative TB notification rates of Cape Town in 2009. Simulated TB notification rate in HIV-negative patients was 1,000/100,000 person-years (pyrs) in children aged < 5 years and decreased to 51/100,000 in children 5-15 years. The peak in early adulthood occurred at 25-29 years (463/100,000 pyrs). After a subsequent decline, simulated TB notification rates gradually increased from the age of 30 years. Sensitivity analyses showed that the dip after the early adult peak was due to the protective effect of latent TB and that retreatment TB was mainly responsible for the rise in TB notification rates from the age of 30 years. Conclusion The protective effect of a first latent infection on subsequent infections and the faster progression in previously treated patients

  8. Tuberculosis in Cape Town: An age-structured transmission model.

    PubMed

    Blaser, Nello; Zahnd, Cindy; Hermans, Sabine; Salazar-Vizcaya, Luisa; Estill, Janne; Morrow, Carl; Egger, Matthias; Keiser, Olivia; Wood, Robin

    2016-03-01

    Tuberculosis (TB) is the leading cause of death in South Africa. The burden of disease varies by age, with peaks in TB notification rates in the HIV-negative population at ages 0-5, 20-24, and 45-49 years. There is little variation between age groups in the rates in the HIV-positive population. The drivers of this age pattern remain unknown. We developed an age-structured simulation model of Mycobacterium tuberculosis (Mtb) transmission in Cape Town, South Africa. We considered five states of TB progression: susceptible, infected (latent TB), active TB, treated TB, and treatment default. Latently infected individuals could be re-infected; a previous Mtb infection slowed progression to active disease. We further considered three states of HIV progression: HIV negative, HIV positive, on antiretroviral therapy. To parameterize the model, we analysed treatment outcomes from the Cape Town electronic TB register, social mixing patterns from a Cape Town community and used literature estimates for other parameters. To investigate the main drivers behind the age patterns, we conducted sensitivity analyses on all parameters related to the age structure. The model replicated the age patterns in HIV-negative TB notification rates of Cape Town in 2009. Simulated TB notification rate in HIV-negative patients was 1000/100,000 person-years (pyrs) in children aged <5 years and decreased to 51/100,000 in children 5-15 years. The peak in early adulthood occurred at 25-29 years (463/100,000 pyrs). After a subsequent decline, simulated TB notification rates gradually increased from the age of 30 years. Sensitivity analyses showed that the dip after the early adult peak was due to the protective effect of latent TB and that retreatment TB was mainly responsible for the rise in TB notification rates from the age of 30 years. The protective effect of a first latent infection on subsequent infections and the faster progression in previously treated patients are the key determinants of the

  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. 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.

  11. Past and recent attempts to model mortality at all ages.

    PubMed

    Hartmann, M

    1987-01-01

    "Most laws of mortality are partial in the sense that they apply only to a broad age group and not to all ages. This paper focuses on three laws of mortality that apply to all ages. Two of them were developed by the actuaries Thiele and Wittstein in the late 19th century. The third, developed by Heligman and Pollard, is of recent origin. The three laws are discussed with references to Scandinavian mortality data. The results suggest that the most recently proposed law can be used for generation of model life tables, for making population projections, simulations, and other statistical work where there is a need for a realistic model of human mortality."

  12. A parameterisation of the soot aging for global climate models

    NASA Astrophysics Data System (ADS)

    Riemer, N.; Vogel, H.; Vogel, B.

    2004-04-01

    The representation of soot in global climate models is desirable since it contributes to both the direct and indirect climate effect. While freshly emitted soot is initially hydrophobic and externally mixed, it can be transferred into an internal mixture by coagulation, condensation or photochemical processes. These aging processes affect the hygroscopic qualities and hence the growth behaviour, the optical properties and eventually the lifetime of the soot particles. However, due to computational limits the aging of soot in global climate models is often only parameterised by an estimated turnover rate resulting in a lifetime of soot of several days. Based on the results of our simulations with a comprehensive mesoscale model, we derive the timescale on which diesel soot is transferred from an external to internal mixture, and propose a parameterisation for the use in global climate models. This parameterisation is applicable to continental conditions in industrialised areas as can be found in Central Europe and North America. For daytime conditions, away from the sources, condensation is dominant and the aging process occurs very fast with a timescale of τ=2 h. During night time condensation is not effective. Then coagulation is the most important aging process and our parameterisation leads to a timescale between 10 h and 40 h.

  13. Computer modelling of age hardening for cast aluminium alloys

    NASA Astrophysics Data System (ADS)

    Wu, Linda; Ferguson, W. George

    2009-08-01

    Age hardening, or precipitation hardening, is one of the most widely adopted techniques for strengthening of aluminium alloys. Although various age hardening models have been developed for aluminium alloys, from the large volume of literature reviewed, it appears that the bulk of the research has been concentrated on wrought aluminium alloys, only a few of the established precipitation models have been applied to the casting aluminium alloys. In the present work, there are two modelling methods that have been developed and applied to the casting aluminium alloys A356 and A357. One is based on the Shercliff-Ashby methodology to produce a process model, by which we mean a mathematical relationship between process variables (alloy composition, ageing temperature and time) and material properties (yield strength or hardness) through microstructure evolution (precipitate radius, volume fraction). The other method is based on the Kampmann and Wagner Numerical (KWN) model which deals with concomitant nucleation, growth and coarsening and is thus capable of predicting the full evolution of the particle size distribution and then a strength model is used to evaluate the resulting change in hardness or yield strength at room temperature by taking into account contributions from lattice resistance, solid solution hardening and precipitation hardening.

  14. Age of stratospheric air and aging by mixing in global models

    NASA Astrophysics Data System (ADS)

    Garny, Hella; Dietmüller, Simone; Plöger, Felix; Birner, Thomas; Bönisch, Harald; Jöckel, Patrick

    2016-04-01

    The Brewer-Dobson circulation is often quantified by the integrated transport measure age of air (AoA). AoA is affected by all transport processes, including transport along the residual mean mass circulation and two-way mixing. A large spread in the simulation of AoA by current global models exists. Using CCMVal-2 and CCMI-1 global model data, we show that this spread can only in small parts be attributed to differences in the simulated residual circulation. Instead, large differences in the "mixing efficiency" strongly contribute to the differences in the simulated AoA. The "mixing efficiency" is defined as the ratio of the two-way mixing mass flux across the subtropical barrier to the net (residual) mass flux, and this mixing efficiency controls the relative increase in AoA by mixing. We derive the mixing efficiency from global model data using the analytical solution of a simplified version of the tropical leaky pipe (TLP) model, in which vertical diffusion is neglected. Thus, it is assumed that only residual mean transport and horizontal two-way mixing across the subtropical barrier controls AoA. However, in global models vertical mixing and numerical diffusion modify AoA, and these processes likely contribute to the differences in the mixing efficiency between models. We explore the contributions of diffusion and mixing on mean AoA by a) using simulations with the tropical leaky pipe model including vertical diffusion and b) explicit calculations of aging by mixing on resolved scales. Using the TLP model, we show that vertical diffusion leads to a decrease in tropical AoA, i.e. counteracts the increase in tropical mean AoA due to horizontal mixing. Thus, neglecting vertical diffusion leads to an underestimation of the mixing efficiency. With explicit calculations of aging by mixing via integration of daily local mixing tendencies along residual circulation trajectories, we explore the contributions of vertical and horizontal mixing for aging by mixing. The

  15. 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.

  16. 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.

  17. 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)

  18. Revisiting dark energy models using differential ages of galaxies

    NASA Astrophysics Data System (ADS)

    Rani, Nisha; Jain, Deepak; Mahajan, Shobhit; Mukherjee, Amitabha; Biesiada, Marek

    2017-03-01

    In this work, we use a test based on the differential ages of galaxies for distinguishing the dark energy models. As proposed by Jimenez and Loeb in [1], relative ages of galaxies can be used to put constraints on various cosmological parameters. In the same vein, we reconstruct H0dt/dz and its derivative (H0d2t/dz2) using a model independent technique called non-parametric smoothing. Basically, dt/dz is the change in the age of the object as a function of redshift which is directly linked with the Hubble parameter. Hence for reconstruction of this quantity, we use the most recent H(z) data. Further, we calculate H0dt/dz and its derivative for several models like Phantom, Einstein de Sitter (EdS), ΛCDM, Chevallier-Polarski-Linder (CPL) parametrization, Jassal-Bagla-Padmanabhan (JBP) parametrization and Feng-Shen-Li-Li (FSLL) parametrization. We check the consistency of these models with the results of reconstruction obtained in a model independent way from the data. It is observed that H0dt/dz as a tool is not able to distinguish between the ΛCDM, CPL, JBP and FSLL parametrizations but, as expected, EdS and Phantom models show noticeable deviation from the reconstructed results. Further, the derivative of H0dt/dz for various dark energy models is more sensitive at low redshift. It is found that the FSLL model is not consistent with the reconstructed results, however, the ΛCDM model is in concordance with the 3σ region of the reconstruction at redshift z>= 0.3.

  19. Network model of human aging: Frailty limits and information measures

    NASA Astrophysics Data System (ADS)

    Farrell, Spencer G.; Mitnitski, Arnold B.; Rockwood, Kenneth; Rutenberg, Andrew D.

    2016-11-01

    Aging is associated with the accumulation of damage throughout a persons life. Individual health can be assessed by the Frailty Index (FI). The FI is calculated simply as the proportion f of accumulated age-related deficits relative to the total, leading to a theoretical maximum of f ≤1 . Observational studies have generally reported a much more stringent bound, with f ≤fmax<1 . The value of fmax in observational studies appears to be nonuniversal, but fmax≈0.7 is often reported. A previously developed network model of individual aging was unable to recover fmax<1 while retaining the other observed phenomenology of increasing f and mortality rates with age. We have developed a computationally accelerated network model that also allows us to tune the scale-free network exponent α . The network exponent α significantly affects the growth of mortality rates with age. However, we are only able to recover fmax by also introducing a deficit sensitivity parameter 1 -q , which is equivalent to a false-negative rate q . Our value of q =0.3 is comparable to finite sensitivities of age-related deficits with respect to mortality that are often reported in the literature. In light of nonzero q , we use mutual information I to provide a nonparametric measure of the predictive value of the FI with respect to individual mortality. We find that I is only modestly degraded by q <1 , and this degradation is mitigated when increasing number of deficits are included in the FI. We also find that the information spectrum, i.e., the mutual information of individual deficits versus connectivity, has an approximately power-law dependence that depends on the network exponent α . Mutual information I is therefore a useful tool for characterizing the network topology of aging populations.

  20. 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

  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. Rotifers as models for the biology of aging.

    PubMed

    Snell, Terry W

    2014-03-01

    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 have

  3. 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.

  4. Estimating child mortality and modelling its age pattern for India.

    PubMed

    Roy, S G

    1989-06-01

    "Using data [for India] on proportions of children dead...estimates of infant and child mortality are...obtained by Sullivan and Trussell modifications of [the] Brass basic method. The estimate of child survivorship function derived after logit smoothing appears to be more reliable than that obtained by the Census Actuary. The age pattern of childhood mortality is suitably modelled by [a] Weibull function defining the probability of surviving from birth to a specified age and involving two parameters of level and shape. A recently developed linearization procedure based on [a] graphical approach is adopted for estimating the parameters of the function."

  5. 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.

  6. 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.

  7. Reassessing risk models for atypical hyperplasia: age may not matter.

    PubMed

    Mazzola, Emanuele; Coopey, Suzanne B; Griffin, Molly; Polubriaginof, Fernanda; Buckley, Julliette M; Parmigiani, Giovanni; Garber, Judy E; Smith, Barbara L; Gadd, Michele A; Specht, Michelle C; Guidi, Anthony; Hughes, Kevin S

    2017-09-01

    The aim of this study was to investigate the influence of age at diagnosis of atypical hyperplasia ("atypia", ductal [ADH], lobular [ALH], or severe ADH) on the risk of developing subsequent invasive breast cancer or ductal carcinoma in situ (DCIS). Using standard survival analysis methods, we retrospectively analyzed 1353 women not treated with chemoprevention among a cohort of 2370 women diagnosed with atypical hyperplasia to determine the risk relationship between age at diagnosis and subsequent breast cancer. For all atypia diagnoses combined, our cohort showed a 5-, 10-, and 15-year risk of invasive breast cancer or DCIS of 0.56, 1.25, and 1.30, respectively, with no significant difference in the (65,75] year age group. For women aged (35,75] years, we observed no significant difference in the 15-year risk of invasive breast cancer or DCIS after atypical hyperplasia, although the baseline risk for a 40-year-old woman is approximately 1/8 the risk of a 70-year-old woman. The risks associated with invasive breast cancer or DCIS for women in our cohort diagnosed with ADH, severe ADH, or ALH, regardless of age, were 7.6% (95% CI 5.9-9.3%) at 5 years, 25.1% (20.7-29.2%) at 10 years, and 40.1% (32.8-46.6%) at 15 years. In contrast to current risk prediction models (e.g., Gail, Tyrer-Cuzick) which assume that the risk of developing breast cancer increases in relation to age at diagnosis of atypia, we found the 15-year cancer risk in our cohort was not significantly different for women between the ages of 35 (excluded) and 75. This implies that the "hits" received by the breast tissue along the "high-risk pathway" to cancer might possibly supersede other factors such as age.

  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. Nothobranchius as a model for aging studies. A review

    PubMed Central

    Lucas-Sánchez, Alejandro; Almaida-Pagán, Pedro Francisco; Mendiola, Pilar; de Costa, Jorge

    2014-01-01

    In recent decades, the increase in human longevity has made it increasingly important to expand our knowledge on aging. To accomplish this, the use of animal models is essential, with the most common being mouse (phylogenetically similar to humans, and a model with a long life expectancy) and Caenorhabditis elegans (an invertebrate with a short life span, but quite removed from us in evolutionary terms). However, some sort of model is needed to bridge the differences between those mentioned above, achieving a balance between phylogenetic distance and life span. Fish of the genus Nothobranchius were suggested 10 years ago as a possible alternative for the study of the aging process. In the meantime, numerous studies have been conducted at different levels: behavioral (including the study of the rest-activity rhythm), populational, histochemical, biochemical and genetic, among others, with very positive results. This review compiles what we know about Nothobranchius to date, and examines its future prospects as a true alternative to the classic models for studies on aging. PMID:25110612

  10. 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.

  11. Automatic age and gender classification using supervised appearance model

    NASA Astrophysics Data System (ADS)

    Bukar, Ali Maina; Ugail, Hassan; Connah, David

    2016-11-01

    Age and gender classification are two important problems that recently gained popularity in the research community, due to their wide range of applications. Research has shown that both age and gender information are encoded in the face shape and texture, hence the active appearance model (AAM), a statistical model that captures shape and texture variations, has been one of the most widely used feature extraction techniques for the aforementioned problems. However, AAM suffers from some drawbacks, especially when used for classification. This is primarily because principal component analysis (PCA), which is at the core of the model, works in an unsupervised manner, i.e., PCA dimensionality reduction does not take into account how the predictor variables relate to the response (class labels). Rather, it explores only the underlying structure of the predictor variables, thus, it is no surprise if PCA discards valuable parts of the data that represent discriminatory features. Toward this end, we propose a supervised appearance model (sAM) that improves on AAM by replacing PCA with partial least-squares regression. This feature extraction technique is then used for the problems of age and gender classification. Our experiments show that sAM has better predictive power than the conventional AAM.

  12. Modeling Manufacturing Impacts on Aging and Reliability of Polyurethane Foams

    SciTech Connect

    Rao, Rekha R.; Roberts, Christine Cardinal; Mondy, Lisa Ann; Soehnel, Melissa Marie; Johnson, Kyle; Lorenzo, Henry T.

    2016-10-01

    Polyurethane is a complex multiphase material that evolves from a viscous liquid to a system of percolating bubbles, which are created via a CO2 generating reaction. The continuous phase polymerizes to a solid during the foaming process generating heat. Foams introduced into a mold increase their volume up to tenfold, and the dynamics of the expansion process may lead to voids and will produce gradients in density and degree of polymerization. These inhomogeneities can lead to structural stability issues upon aging. For instance, structural components in weapon systems have been shown to change shape as they age depending on their molding history, which can threaten critical tolerances. The purpose of this project is to develop a Cradle-to-Grave multiphysics model, which allows us to predict the material properties of foam from its birth through aging in the stockpile, where its dimensional stability is important.

  13. Nothobranchius furzeri: A Model for Aging Research and More.

    PubMed

    Platzer, Matthias; Englert, Christoph

    2016-09-01

    The short-lived killifish Nothobranchius furzeri inhabits ephemeral ponds in southeastern Africa and is characterized by rapid growth and early sexual maturation. With respect to the molecular, cellular, and integrative traits of aging, N. furzeri shows significant similarities to mammals, including humans. Recently, reference sequences for the N. furzeri genome have been published. Also, methods for transgenesis and genomic engineering have been established. In this review we discuss why the killifish is a valuable model for aging research and what we have learned from the genome sequence. The respective insights are not limited to the biology of aging but are also relevant for developmental biology and the evolution of sex determination. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Genetic mouse models of brain ageing and Alzheimer's disease.

    PubMed

    Bilkei-Gorzo, Andras

    2014-05-01

    Progression of brain ageing is influenced by a complex interaction of genetic and environmental factors. Analysis of genetically modified animals with uniform genetic backgrounds in a standardised, controlled environment enables the dissection of critical determinants of brain ageing on a molecular level. Human and animal studies suggest that increased load of damaged macromolecules, efficacy of DNA maintenance, mitochondrial activity, and cellular stress defences are critical determinants of brain ageing. Surprisingly, mouse lines with genetic impairment of anti-oxidative capacity generally did not show enhanced cognitive ageing but rather an increased sensitivity to oxidative challenge. Mouse lines with impaired mitochondrial activity had critically short life spans or severe and rapidly progressing neurodegeneration. Strains with impaired clearance in damaged macromolecules or defects in the regulation of cellular stress defences showed alterations in the onset and progression of cognitive decline. Importantly, reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body. Brain ageing is accompanied by an increased risk of developing Alzheimer's disease. Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease. Generally, therapeutic strategies effective against Alzheimer's disease in humans were also active in the Tg2576, APP23, APP/PS1 and 5xFAD lines, but a large number of false positive findings were also reported. The 3xtg AD model likely has the highest face and construct validity but further studies are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Autophagy and ageing: insights from invertebrate model organisms.

    PubMed

    Lionaki, Eirini; Markaki, Maria; Tavernarakis, Nektarios

    2013-01-01

    Ageing in diverse species ranging from yeast to humans is associated with the gradual, lifelong accumulation of molecular and cellular damage. Autophagy, a conserved lysosomal, self-destructive process involved in protein and organelle degradation, plays an essential role in both cellular and whole-animal homeostasis. Accumulating evidence now indicates that autophagic degradation declines with age and this gradual reduction of autophagy might have a causative role in the functional deterioration of biological systems during ageing. Indeed, loss of autophagy gene function significantly influences longevity. Moreover, genetic or pharmacological manipulations that extend lifespan in model organisms often activate autophagy. Interestingly, conserved signalling pathways and environmental factors that regulate ageing, such as the insulin/IGF-1 signalling pathway and oxidative stress response pathways converge on autophagy. In this article, we survey recent findings in invertebrates that contribute to advance our understanding of the molecular links between autophagy and the regulation of ageing. In addition, we consider related mechanisms in other organisms and discuss their similarities and idiosyncratic features in a comparative manner.

  16. 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.

  17. [The use of biological age on mental work capacity model in accelerated aging assessment of professional lorry-drivers].

    PubMed

    Bashkireva, A S

    2012-01-01

    The studies of biological age, aging rate, mental work capacity in professional drivers were conducted. The examination revealed peculiarities of system organization of functions determining the mental work capacity levels. Dynamics of the aging process of professional driver's organism in relation with calendar age and driving experience were shown using the biological age model. The results point at the premature decrease of the mental work capacity in professional drivers. It was proved, that premature age-related changes of physiologic and psychophysiologic indices in drivers are just "risk indicators", while long driving experience is a real risk factor, accelerating the aging process. The "risk group" with manifestations of accelerating aging was observed in 40-49-year old drivers with 15-19 years of professional experience. The expediency of using the following methods for the age rate estimation according to biologic age indices and necessity of prophylactic measures for premature and accelerated aging prevention among working population was demonstrated.

  18. Annual fish as a genetic model for aging.

    PubMed

    Herrera, Michael; Jagadeeswaran, Pudur

    2004-02-01

    Advancement in the genetics of aging and identification of longevity genes has been largely due to the model organisms such as Caenorhabditis elegans and Drosophila melanogaster. However, knowledge gained from these invertebrates will not be able to identify vertebrate-specific longevity genes. The mouse has a relatively long life span of about 3 years, which limits its utility for screening of longevity genes. Fish have been used in aging studies. However, systematic comparison of survivorship curves for fish is lacking. In this study, we compared the survivorship curves of zebrafish and 2 different annual fish, namely, Cynolebias nigripinnis and Nothobranchius rachovii. These studies established that Nothobranchius rachovii has the shortest life span (8.5 months, at which time 10% of population remains). We also established that it is possible to breed Nothobranchius rachovii under laboratory conditions, and showed that their embryos can be stored for several months and hatched at any time by adding water. In addition, we have isolated 31 cDNA markers out of 71 attempted amplifications based on corresponding homologous genomic sequences in zebrafish and Fugu available from public databases, suggesting that approximately 40% of the genes from Nothobranchius rachovii could be easily isolated. Thus, the ability to be bred under laboratory conditions and the availability of cDNA markers for mapping, along with the major advantage of a relatively short life span, make Nothobranchius rachovii an attractive vertebrate genetic model for aging over other available vertebrate models.

  19. A behavioural dynamic model of the relative age effect.

    PubMed

    Pierson, Kawika; Addona, Vittorio; Yates, Philip

    2014-01-01

    The relationship between date of birth and success in a variety of sports, including hockey, is well established. This phenomenon is known as the relative age effect (RAE). We model the RAE in Canadian youth hockey as a positive feedback loop where an initial age advantage is reinforced through additional training and playing opportunities based on perceived skill superiority. The same causal mechanism leads to a higher quit rate for relatively younger players. Our model effectively replicates the birth month distribution of Canadian National Hockey League players (R2 = 86.79%) when driven by Canadian birth distributions. We use this model to evaluate three policies that aim to lessen the RAE. All of the policies reduce the RAE with a significant delay. The most effective policy is a combination of providing additional support to age disadvantaged children and rotating the cut-off date for youth leagues between January 1st and July 1st annually. In equilibrium, this approach leads to a 96% reduction in the RAE compared to the base case.

  20. 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.

  1. An age-structured model with delay mortality.

    PubMed

    Tchuenche, J M

    2005-09-01

    Many species experience aperiodic mortality. Yet, there is little or no understanding of how this event affects population dynamics. We have considered one of the most simple class of age-structured models, namely, the MacKendrick Von Foerster type equations with suitable modifications to suit the purpose of this study. The main result shows the effect of delay in the estimate of the population. If the delay parameter is taken as a period, then the model equations describe the dynamics of seasonal insects such as locusts whose large population decreases very fast.

  2. Mixed models, linear dependency, and identification in age-period-cohort models.

    PubMed

    O'Brien, Robert M

    2017-07-20

    This paper examines the identification problem in age-period-cohort models that use either linear or categorically coded ages, periods, and cohorts or combinations of these parameterizations. These models are not identified using the traditional fixed effect regression model approach because of a linear dependency between the ages, periods, and cohorts. However, these models can be identified if the researcher introduces a single just identifying constraint on the model coefficients. The problem with such constraints is that the results can differ substantially depending on the constraint chosen. Somewhat surprisingly, age-period-cohort models that specify one or more of ages and/or periods and/or cohorts as random effects are identified. This is the case without introducing an additional constraint. I label this identification as statistical model identification and show how statistical model identification comes about in mixed models and why which effects are treated as fixed and which are treated as random can substantially change the estimates of the age, period, and cohort effects. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  3. 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.

  4. 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.

  5. Modelling safety of multistate systems with ageing components

    SciTech Connect

    Kołowrocki, Krzysztof; Soszyńska-Budny, Joanna

    2016-06-08

    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.

  6. Chronic depression as a model disease for cerebral aging.

    PubMed

    Bewernick, Bettina H; Schlaepfer, Thomas E

    2013-03-01

    Conceptualizations of the underlying neurobiology of major depression have changed their focus from dysfunctions of neurotransmission to dysfunctions of neurogenesis and neuroprotection. The "neurogenesis hypothesis of depression" posits that changes in the rate of neurogenesis are the underlying mechanism in the pathology and treatment of major depression. Stress, neuroinflammation, dysfunctional insulin regulation, oxidative stress, and alterations in neurotrophic factors possibly contribute to the development of depression. The influence of antidepressant therapies, namely pharmacotherapy and neuroprotectants, on cellular plasticity are summarized. A dysfunction of complex neuronal networks as a consequence of neural degeneration in neuropsychiatric diseases has led to the application of deep brain stimulation. We discuss the way depression seen in the light of the neurogenesis hypothesis can be used as a model disease for cerebral aging. A common pathological mechanism in depression and cerebral aging-a dysfunction of neuroprotection and neurogenesis-is discussed. This has implications for new treatment methods.

  7. A model for nonexponential relaxation and aging in dissipative systems

    NASA Astrophysics Data System (ADS)

    Pérez-Madrid, A.

    2005-06-01

    The nonexponential relaxation and aging inherent to complex dynamics manifested in a wide variety of dissipative systems are analyzed through a model of diffusion in phase space in the presence of a nonconservative force. The action of this force establishes a heat flow which maintains the system away from equilibrium. The inability of the system to find its equilibrium state becomes apparent through the presence of an effective temperature field. This is the temperature of the stationary nonequilibrium state reached by the system satisfying a generalized version of the fluctuation-dissipation theorem. The presence of a nonequilibrium temperature leads to a hierarchy of relaxation times responsible for the aging phenomena and to a relation similar to the Vogel-Fulcher-Tammann law [H. Vogel, Phys. Z. 22, 645 (1921); G. S. Fulcher, J. Am. Ceram. Soc. 8, 339 (1925); 8, 789 (1925); G. Tammann and W. Hesse, Z. Anorg. Allg. Chem. 156, 245 (1926)].

  8. 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

  9. 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

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

    PubMed

    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

  11. 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

  12. 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

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

    PubMed

    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.

  14. 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

  15. A new age-related model for blood stroke volume.

    PubMed

    Chuiko, G P; Dvornik, O V; Shyian, S I; Baganov, Ye A

    2016-12-01

    A new computer model for systolic pulse waves within the cardiovascular system is presented. The emphasis was made on blood stroke volume (BS). The new waveform for pulse wave demands the re-computing of the BS. The authors showed the applicability of suggested model for arterial aging problem. Suggested model is based on the well-known Korteweg-de Vries (KdV) equation. Instead of the common accepted solitary wave, the periodical cnoidal wave is used. Both waves are exact solutions of the KdV equation. The cnoidal waves are described by the Jacobi elliptic functions. Depending on a specific parameter called the elliptic module, m (0≤m≤1), these functions can be either harmonic or hyperbolic type. The explicit expression for the dimensionless BS was obtained. The dimensionless BS depends, as was found, on the elliptic module only. Dimensional analysis demonstrates the dimensionless BS has limited range of variation. This allows the direct estimation of elliptic module that turns out to be close but not exact equal to one. It is shown, that correct calculations of BS can not be done at m=1 (corresponds to simpler soliton model), and the periodicity of pulse waves has to be taken into consideration. Only the cnoidal model with the limited wavelength provides the correct computing of the BS. The natural bounds of dimensionless BS were found for the first time. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. 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.

  17. Sundowning syndrome in aging and dementia: research in mouse models.

    PubMed

    Bedrosian, Tracy A; Nelson, Randy J

    2013-05-01

    Both normal aging and dementia are associated with altered circadian regulation of physiology and behavior. Elderly individuals and dementia patients commonly experience disrupted sleep-wake cycles, which may lead to psychomotor agitation, confusion, and wandering. These behaviors are disruptive to both patients and caregivers. Sundowning syndrome, which encompasses many of these behaviors, is characterized by a temporal pattern in the severity of symptoms, usually expressed as worse during the late afternoon or evening. Other than antipsychotic medications, off-label medications, and restraint, few treatment options are available. The aim of this paper is to review mouse studies of circadian behavioral disturbances relevant to sundowning, in order to determine potential models for studying the mechanisms of sundowning syndrome. The emergence of a useful mouse model should facilitate the development of novel therapeutic approaches. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Stratospheric age-of-air trends: Reanalysis v. climate models

    NASA Astrophysics Data System (ADS)

    Monge-Sanz, Beatriz; Dee, Dick; Hersbach, Hans; Simmons, Adrian; Parodi, Jose A.; Haenel, Florian; Stiller, Gabriele; Chipperfield, Martyn; Feng, Wuhu

    2017-04-01

    Knowing how the Brewer-Dobson circulation (BDC) has evolved in the recent past and will continue to evolve is crucial for atmospheric composition in the UTLS and stratosphere, as well as for feedbacks with climate. Most climate models have predicted an intensification of the stratospheric circulation with the increase in greenhouse gases concentrations, which translates into younger age-of-air (AoA) values modelled in the stratosphere. Nevertheless, balloon and satellite observations do not agree with the widespread modelled trend towards younger age-of-air for the recent past (Engel et al., 2009; Stiller et al., 2012; Haenel et al. 2015). Furthermore, a few recent studies with chemistry transport models (CTMs) driven by ERA-Interim reanalysis (Dee et al., 2011) have also shown agreement with the observed trends and not with those from climate models (e.g. Monge-Sanz et al., 2012; Diallo et al., 2012; Ploeger et al., 2015). To increase our confidence in climate-chemistry projections, the causes for the apparent disagreement in trends of age-of-air between observations and most climate models need to be identified. In this study we have carried out simulations with a CTM to assess the stratospheric circulation with the ERA-Interim dataset produced by the European Centre for Medium-Range Weather Forecasts (ECMWF), as well as with data produced from an equivalent climate system. AoA trends from our model results with ERA-Interim fields are in good agreement with the recent age-of-air studies based on observations and differ from the results we obtain with the corresponding climate data. We will show that biases in the mean AoA values are also different for these datasets compared to observations. In addition we have used recent experimental datasets from the ECMWF system to identify potential causes for the differences in AoA distribution and trends. The validation of our model results has been performed against the new revised AoA dataset based on MIPAS SF6

  19. 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.

  20. Lattice percolation approach to 3D modeling of tissue aging

    NASA Astrophysics Data System (ADS)

    Gorshkov, Vyacheslav; Privman, Vladimir; Libert, Sergiy

    2016-11-01

    We describe a 3D percolation-type approach to modeling of the processes of aging and certain other properties of tissues analyzed as systems consisting of interacting cells. Lattice sites are designated as regular (healthy) cells, senescent cells, or vacancies left by dead (apoptotic) cells. The system is then studied dynamically with the ongoing processes including regular cell dividing to fill vacant sites, healthy cells becoming senescent or dying, and senescent cells dying. Statistical-mechanics description can provide patterns of time dependence and snapshots of morphological system properties. The developed theoretical modeling approach is found not only to corroborate recent experimental findings that inhibition of senescence can lead to extended lifespan, but also to confirm that, unlike 2D, in 3D senescent cells can contribute to tissue's connectivity/mechanical stability. The latter effect occurs by senescent cells forming the second infinite cluster in the regime when the regular (healthy) cell's infinite cluster still exists.

  1. Constraints on Pacific midplate swells from global depth-age and heat flow-age models

    NASA Astrophysics Data System (ADS)

    Stein, Carol A.; Stein, Seth

    Oceanic midplate swells are identified by shallow seafloor depths. In turn, models of the processes giving rise to these regions rely on assessments of how their depths, surface heat flow, and flexural properties differ from those for lithosphere which is presumed not to have been affected by these processes. Such comparisons have been inhibited because reference thermal models, which are assumed to describe unperturbed lithosphere, predict deeper depths and lower heat flow than typically observed for lithosphere older than 70 Ma. As a result, both depth and heat flow anomalies can be overestimated. To address this difficulty, we have derived model GDH1 (Global Depth and Heat flow) by joint fitting of heat flow and bathymetry. GDH1, which has a hotter and thinner lithosphere than previous models, fits the depth and heat flow data significantly better, including the data from older lithosphere previously treated as anomalous. It also provides an improved fit to depth-to-basement data for ocean drilling sites, and to geoid offsets across fracture zones. The improved fit occurs for depth-age data from both the DBDB-5 digital bathymetry, and from regional medians from ship tracks, which yield comparable depth-age curves. We use GDH1 to study three classes of midplate swells: the Hawaiian and other hot spot swells, the Darwin Rise area of widespread Cretaceous volcanism, and the Superswell, considered a present analogue to the Darwin Rise. Heat flow on the Hawaiian swell, though anomalously high with respect to previous reference models, is at most slightly high relative to GDH1. The situation is similar for the Bermuda, Cape Verde, and Crozet hot spots. The absence of a significant heat flow anomaly favors a primarily dynamic, rather than thermal, origin for these swells. Similarly, the present depths and heat flow for the Darwin Rise are consistent with GDH1, although they were anomalous with respect to previous reference models. The depth and heat flow data thus

  2. 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

  3. 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

  4. 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

  5. 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

  6. Modeling age-of-onset: Cox model with latent major gene effects

    SciTech Connect

    Li, H.; Thompson, E.A.

    1994-09-01

    Analysis of age-of-onset is a key factor in the segregation and linkage analysis of complex genetic traits, but is complicated by the censoring of unaffected individuals. Most previous work has used parametric distributional assumptions, but it is hard to characterize the distribution of age-of-onset by a single distribution. Other approaches discretize age-of-onset and use logistic regression to model incidence; this approach does not use the information fully. Frailty models have been used for age-of-oset in the biostatistics literature, but these models do not lend themselves to modeling the correlations due to genetic effects which segregate within a family. Here, we propose use of the Cox model with latent major gene effects; conditional on the major genotypes, Cox`s proportional hazards model is used for age-of-onset for each individual. This is a semiparametric model; we do not specify the baseline hazard function. Likelihood analysis of such models is restricted by the difficulty in evaluating of maximizing the likelihood, especially when data are available for some of the members of an extended pedigree. Markov chain Monte Carlo permits genotypic configurations to be realized from the posterior distributions given a current model and the observed data. Hence methods for likelihood analysis can be developed: Monte Carlo EM is used for estimation of the parameters and their variance-covariance matrix. Markers and observed covariates are easily incorporated into this analysis. We present the model, methods for likelihood analysis and the results of a simulation study. The results are comparable with those based on a Cox model with known genotypic dependence in a pedigree. An early-onset Alzheimer`s pedigree and some breast cancer pedigrees have been used as real data examples. Some possible extensions are also discussed.

  7. 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

  8. Age and structure of a model vapour-deposited glass

    NASA Astrophysics Data System (ADS)

    Reid, Daniel R.; Lyubimov, Ivan; Ediger, M. D.; de Pablo, Juan J.

    2016-10-01

    Glass films prepared by a process of physical vapour deposition have been shown to have thermodynamic and kinetic stability comparable to those of ordinary glasses aged for thousands of years. A central question in the study of vapour-deposited glasses, particularly in light of new knowledge regarding anisotropy in these materials, is whether the ultra-stable glassy films formed by vapour deposition are ever equivalent to those obtained by liquid cooling. Here we present a computational study of vapour deposition for a two-dimensional glass forming liquid using a methodology, which closely mimics experiment. We find that for the model considered here, structures that arise in vapour-deposited materials are statistically identical to those observed in ordinary glasses, provided the two are compared at the same inherent structure energy. We also find that newly deposited hot molecules produce cascades of hot particles that propagate far into the film, possibly influencing the relaxation of the material.

  9. Age and structure of a model vapour-deposited glass

    PubMed Central

    Reid, Daniel R.; Lyubimov, Ivan; Ediger, M. D.; de Pablo, Juan J.

    2016-01-01

    Glass films prepared by a process of physical vapour deposition have been shown to have thermodynamic and kinetic stability comparable to those of ordinary glasses aged for thousands of years. A central question in the study of vapour-deposited glasses, particularly in light of new knowledge regarding anisotropy in these materials, is whether the ultra-stable glassy films formed by vapour deposition are ever equivalent to those obtained by liquid cooling. Here we present a computational study of vapour deposition for a two-dimensional glass forming liquid using a methodology, which closely mimics experiment. We find that for the model considered here, structures that arise in vapour-deposited materials are statistically identical to those observed in ordinary glasses, provided the two are compared at the same inherent structure energy. We also find that newly deposited hot molecules produce cascades of hot particles that propagate far into the film, possibly influencing the relaxation of the material. PMID:27762262

  10. 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.

  11. Does active ageing contribute to life satisfaction for older people? Testing a new model of active ageing.

    PubMed

    Marsillas, Sara; De Donder, Liesbeth; Kardol, Tinie; van Regenmortel, Sofie; Dury, Sarah; Brosens, Dorien; Smetcoren, An-Sofie; Braña, Teresa; Varela, Jesús

    2017-09-01

    Several debates have emerged across the literature about the conceptualisation of active ageing. The aim of this study is to develop a model of the construct that is focused on the individual, including different elements of people's lives that have the potential to be modified by intervention programs. Moreover, the paper examines the contributions of active ageing to life satisfaction, as well as the possible predictive role of coping styles on active ageing. For this purpose, a representative sample of 404 Galician (Spain) community-dwelling older adults (aged ≥60 years) were interviewed using a structured survey. The results demonstrate that the proposed model composed of two broad categories is valid. The model comprises status variables (related to physical, psychological, and social health) as well as different types of activities, called processual variables. This model is tested using partial least squares (PLS) regression. The findings show that active ageing is a fourth-order, formative construct. In addition, PLS analyses indicate that active ageing has a moderate and positive path on life satisfaction and that coping styles may predict active ageing. The discussion highlights the potential of active ageing as a relevant concept for people's lives, drawing out policy implications and suggestions for further research.

  12. 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.

  13. Improved age modelling and high-precision age estimates of late Quaternary tephras, for accurate palaeoclimate reconstruction

    NASA Astrophysics Data System (ADS)

    Blockley, Simon P. E.; Bronk Ramsey, C.; Pyle, D. M.

    2008-10-01

    The role of tephrochronology, as a dating and stratigraphic tool, in precise palaeoclimate and environmental reconstruction, has expanded significantly in recent years. The power of tephrochronology rests on the fact that a tephra layer can stratigraphically link records at the resolution of as little as a few years, and that the most precise age for a particular tephra can be imported into any site where it is found. In order to maximise the potential of tephras for this purpose it is necessary to have the most precise and robustly tested age estimate possible available for key tephras. Given the varying number and quality of dates associated with different tephras it is important to be able to build age models to test competing tephra dates. Recent advances in Bayesian age modelling of dates in sequence have radically extended our ability to build such stratigraphic age models. As an example of the potential here we use Bayesian methods, now widely applied, to examine the dating of some key Late Quaternary tephras from Italy. These are: the Agnano Monte Spina Tephra (AMST), the Neapolitan Yellow Tuff (NYT) and the Agnano Pomici Principali (APP), and all of them have multiple estimates of their true age. Further, we use the Bayesian approaches to generate a revised mixed radiocarbon/varve chronology for the important Lateglacial section of the Lago Grande Monticchio record, as a further illustration of what can be achieved by a Bayesian approach. With all three tephras we were able to produce viable model ages for the tephra, validate the proposed 40Ar/ 39Ar age ranges for these tephras, and provide relatively high precision age models. The results of the Bayesian integration of dating and stratigraphic information, suggest that the current best 95% confidence calendar age estimates for the AMST are 4690-4300 cal BP, the NYT 14320-13900 cal BP, and the APP 12380-12140 cal BP.

  14. Mitochondrial damage and ageing using skin as a model organ.

    PubMed

    Hudson, Laura; Bowman, Amy; Rashdan, Eyman; Birch-Machin, Mark A

    2016-11-01

    Ageing describes the progressive functional decline of an organism over time, leading to an increase in susceptibility to age-related diseases and eventually to death, and it is a phenomenon observed across a wide range of organisms. Despite a vast repertoire of ageing studies performed over the past century, the exact causes of ageing remain unknown. For over 50 years it has been speculated that mitochondria play a key role in the ageing process, due mainly to correlative data showing an increase in mitochondrial dysfunction, mitochondrial DNA (mtDNA) damage, and reactive oxygen species (ROS) with age. However, the exact role of the mitochondria in the ageing process remains unknown. The skin is often used to study human ageing, due to its easy accessibility, and the observation that the ageing process is able to be accelerated in this organ via environmental insults, such as ultra violet radiation (UVR). This provides a useful tool to investigate the mechanisms regulating ageing and, in particular, the role of the mitochondria. Observations from dermatological and photoageing studies can provide useful insights into chronological ageing of the skin and other organs such as the brain and liver. Moreover, a wide range of diseases are associated with ageing; therefore, understanding the cause of the ageing process as well as regulatory mechanisms involved could provide potentially advantageous therapeutic targets for the prevention or treatment of such diseases. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. 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).

  16. Aging and contextual binding: Modeling recency and lag-recency effects with the temporal context model

    PubMed Central

    Howard, Marc W.; Kahana, Michael J.; Wingfield, Arthur

    2006-01-01

    Normal aging has been shown to spare recency effects in the initiation of free recall while disrupting temporally-defined associations. The temporal context model (TCM) explains recency and temporally-defined associations as consequences of a gradually-changing context signal and recovery of those contextual states, respectively. Here we extend TCM to account for the dissociation between recency and temporally defined associations in older adults. Modeling results suggested that the effect of aging was restricted to a decrement in the ability of items to recover the temporal contexts in which they were presented, a function that has been hypothesized to depend on the hippocampus. PMID:17048728

  17. Aging and contextual binding: modeling recency and lag recency effects with the temporal context model.

    PubMed

    Howard, Marc W; Kahana, Michael J; Wingfield, Arthur

    2006-06-01

    Normal aging has been shown to spare recency effects in the initiation of free recall while disrupting temporally defined associations. The temporal context model (TCM) explains recency and temporally defined associations as consequences of a gradually changing context signal and recovery of those contextual states, respectively. Here we extend TCM to account for the dissociation between recency and temporally defined associations in younger and older adults. Modeling results suggested that the effect of aging was restricted to a decrement in the ability of items to recover the temporal contexts in which they were presented, a function that has been hypothesized to depend on the hippocampus.

  18. 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

  19. 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.

  20. Frontiers of model animals for neuroscience: two prosperous aging model animals for promoting neuroscience research.

    PubMed

    Ito, Koichi

    2013-01-01

    A model animal showing spontaneous onset is a useful tool for investigating the mechanism of disease. Here, I would like to introduce two aging model animals expected to be useful for neuroscience research: the senescence-accelerated mouse (SAM) and the klotho mouse. The SAM was developed as a mouse showing a senescence-related phenotype such as a short lifespan or rapid advancement of senescence. In particular, SAMP8 and SAMP10 show age-related impairment of learning and memory. SAMP8 has spontaneous spongy degeneration in the brain stem and spinal cord with aging, and immunohistochemical studies reveal excess protein expression of amyloid precursor protein and amyloid β in the brain, indicating that SAMP8 is a model for Alzheimer's disease. SAMP10 also shows age-related impairment of learning and memory, but it does not seem to correspond to Alzheimer's disease because senile plaques primarily composed of amyloid β or neurofibrillary tangles primarily composed of phosphorylated tau were not observed. However, severe atrophy in the frontal cortex, entorhinal cortex, amygdala, and nucleus accumbens can be seen in this strain in an age-dependent manner, indicating that SAMP10 is a model for normal aging. The klotho mouse shows a phenotype, regulated by only one gene named α-klotho, similar to human progeria. The α-klotho gene is mainly expressed in the kidney and brain, and oxidative stress is involved in the deterioration of cognitive function of the klotho mouse. These animal models are potentially useful for neuroscience research now and in the near future.

  1. Modeling of aging in plutonium by molecular dynamics

    NASA Astrophysics Data System (ADS)

    Pochet, P.

    2003-04-01

    The origin of aging in plutonium lies in the extra formation of defects due to self-decay of 239Pu. The modeling of the formation of these defects is achieved by molecular dynamics (MD). In this work a simple EAM potential has been used to study defects formation in fcc plutonium and a 2 keV cascade is analyzed. A large pressure wave is generated around the cascade core. In the used MD code the pressure wave is not absorbed at the box boundaries and due to the periodic boundary conditions, the use of a very large box is crucial in order to avoid interaction of the cascade with itself. More than 800 000 atoms are needed to deal with this small 2 keV cascade without any artifacts. This effect comes from the very low bulk modulus of fcc Pu. The relative long time to achieve the annealing is also connected to the bulk modulus. These results are discussed in terms of large pressure wave: alloying effects are predicted using that viewpoint.

  2. Testing Multidimensional Models of Youth Civic Engagement: Model Comparisons, Measurement Invariance, and Age Differences

    ERIC Educational Resources Information Center

    Wray-Lake, Laura; Metzger, Aaron; Syvertsen, Amy K.

    2017-01-01

    Despite recognition that youth civic engagement is multidimensional, different modeling approaches are rarely compared or tested for measurement invariance. Using a diverse sample of 2,467 elementary, middle, and high school-aged youth, we measured eight dimensions of civic engagement: social responsibility values, informal helping, political…

  3. Histone methylation and aging: Lessons learned from model systems

    PubMed Central

    McCauley, Brenna S.; Dang, Weiwei

    2014-01-01

    Aging induces myriad cellular and, ultimately, physiological changes that cause a decline in an organism's functional capabilities. Although the aging process and pathways that regulate it have been extensively studied, only in the last decade have we begun to appreciate that dynamic histone methylation may contribute to this process. In this review, we discuss recent work implicating histone methylation in aging. Loss of certain histone methyltransferases and demethylases changes lifespan in invertebrates, and alterations in histone methylation in aged organisms regulate lifespan and aging phenotypes, including oxidative stress-induced hormesis in yeast, insulin signaling in Caenorhabiditis elegans and mammals, and the senescence-associated secretory phenotype in mammals. In all cases where histone methylation has been shown to impact aging and aging phenotypes, it does so by regulating transcription, suggesting that this is a major mechanism of its action in this context. Histone methylation additionally regulates or is regulated by other cellular pathways that contribute to or combat aging. Given the numerous processes that regulate aging and histone methylation, and are in turn regulated by them, the role of histone methylation in aging is almost certainly underappreciated. PMID:24859460

  4. Developing mouse models of aging: a consideration of strain differences in age-related behavioral and neural parameters.

    PubMed

    Ingram, D K; Jucker, M

    1999-01-01

    Increased interest is emerging for using mouse models to assess the genetics of brain aging and age-related neurodegenerative diseases. Despite this demand, relatively little information is available on aging in behavioral or neuromorphological parameters in various mouse strains that are being used to create transgenic and null mutant mice. We review several issues regarding selection of appropriate strains as follows: (1) Does the behavioral parameter exhibit a significant age by strain interaction? (2) Do the strains differ in lifespan? (3) Are there potential intervening variables, such as strain-specific performance strategies or disease, in the behavioral task being investigated that would confound the desired conclusions? (4) Does the behavioral difference have an underlying neural correlate? In this context we present a conceptual model pertaining to the selection of mouse strains and behavioral parameters for genetic analyses. We also review the importance of applying stereological techniques for determining age-related structural changes in the mouse brain as well as the potential value of a database that would catalog this information. Thus, our intention is to underscore the growing importance of mouse models of brain aging and the concomitant need for additional information about mouse aging in general.

  5. 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

  6. Chronic kidney disease: a clinical model of premature aging.

    PubMed

    Stenvinkel, Peter; Larsson, Tobias E

    2013-08-01

    Premature aging is a process associated with a progressive accumulation of deleterious changes over time, an impairment of physiologic functions, and an increase in the risk of disease and death. Regardless of genetic background, aging can be accelerated by the lifestyle choices and environmental conditions to which our genes are exposed. Chronic kidney disease is a common condition that promotes cellular senescence and premature aging through toxic alterations in the internal milieu. This occurs through several mechanisms, including DNA and mitochondria damage, increased reactive oxygen species generation, persistent inflammation, stem cell exhaustion, phosphate toxicity, decreased klotho expression, and telomere attrition. Because recent evidence suggests that both increased local signaling of growth factors (through the nutrient-sensing mammalian target of rapamycin) and decreased klotho expression are important modulators of aging, interventions that target these should be tested in this prematurely aged population. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  7. Block Constraints in Age-Period-Cohort Models with Unequal-Width Intervals

    ERIC Educational Resources Information Center

    Luo, Liying; Hodges, James S.

    2016-01-01

    Age-period-cohort (APC) models are designed to estimate the independent effects of age, time periods, and cohort membership. However, APC models suffer from an identification problem: There are no unique estimates of the independent effects that fit the data best because of the exact linear dependency among age, period, and cohort. Among methods…

  8. 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.

  9. Autophagy in kidney disease and aging: lessons from rodent models.

    PubMed

    Lenoir, Olivia; Tharaux, Pierre-Louis; Huber, Tobias B

    2016-11-01

    Autophagy is a highly regulated lysosomal protein degradation pathway that removes protein aggregates and damaged or excess organelles to maintain intracellular homeostasis and cell integrity. Dysregulation of autophagy is involved in the pathogenesis of a variety of metabolic and age-related diseases. Growing evidence suggests that autophagy is implicated in cell injury during renal diseases, both in the tubulointerstitial compartment and in glomeruli. Nevertheless, the impact of autophagy on renal disease progression and aging is still not fully understood. This review summarizes the recent advances in understanding the role of autophagy for kidney disease and aging. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  10. A model of suicidal ideation in adults aging with HIV.

    PubMed

    Vance, David E; Moneyham, Linda; Fordham, Pam; Struzick, Thomas C

    2008-01-01

    Continuing advances in antiretroviral therapy are increasing survival and longevity for people living with HIV. However, factors related to depression and suicidal ideation associated with aging and HIV may mean that the synergistic effects of aging with HIV could place many adults at undue risk for these conditions. Such factors include ageism and stigma, loneliness/decreased social support, neurological changes, declining health, fatigue, changes in appearance, and financial distress. Potential interventions that address these factors are needed to abate depression and prevent suicidal ideation. Nurses are in key positions to identify and intervene with HIV-infected and aging patients who may be at risk for depression and suicidal ideation.

  11. Radiocarbon age modeling: dissolution, bioturbation and sediment redistribution

    NASA Astrophysics Data System (ADS)

    Mekik, F.

    2012-12-01

    We generated radiocarbon dates for whole and fragmented planktonic foraminifer tests (by several species) from a series of core tops which have experienced little dissolution from two depth transects (Rio Grande Rise - RIO and Ontong Java Plateau - OJP) and from down core records from three tropical Pacific cores with significantly different sediment accumulation rates. We also generated new radiocarbon data from both whole Globorotalia menardii shells and its fragments within the same sediments in order to test the robustness of a calcite dissolution proxy, the G. menardii Fragmentation Index (MFI). Our data reveal that the ages of all sediment components increase with increasing dissolution. This is most easily observable on RIO where the age offset between the shallowest samples and deepest samples is ~5 ka, while the mixing ages of the cores are ~1.9ka. This result is new and significant because previous work has always been in the tropical Pacific where bioturbation and mixing ages are high. Furthermore, two of the 7 core top samples from RIO revealed whole G. menardii shells of Glacial age. This is surprising because G. menardiis have not been reported in sediments from the Atlantic Ocean older than 13,000 years. Lastly, we found that the higher the sediment accumulation rate, the closer the age offset between G. menradii whole shells and its fragments in the same sediments both on RIO and OJP. This is important for the interpretation of down core work with MFI.

  12. 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.

  13. 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

  14. 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.

  15. The ageing lens and cataract: a model of normal and pathological ageing.

    PubMed

    Michael, R; Bron, A J

    2011-04-27

    Cataract is a visible opacity in the lens substance, which, when located on the visual axis, leads to visual loss. Age-related cataract is a cause of blindness on a global scale involving genetic and environmental influences. With ageing, lens proteins undergo non-enzymatic, post-translational modification and the accumulation of fluorescent chromophores, increasing susceptibility to oxidation and cross-linking and increased light-scatter. Because the human lens grows throughout life, the lens core is exposed for a longer period to such influences and the risk of oxidative damage increases in the fourth decade when a barrier to the transport of glutathione forms around the lens nucleus. Consequently, as the lens ages, its transparency falls and the nucleus becomes more rigid, resisting the change in shape necessary for accommodation. This is the basis of presbyopia. In some individuals, the steady accumulation of chromophores and complex, insoluble crystallin aggregates in the lens nucleus leads to the formation of a brown nuclear cataract. The process is homogeneous and the affected lens fibres retain their gross morphology. Cortical opacities are due to changes in membrane permeability and enzyme function and shear-stress damage to lens fibres with continued accommodative effort. Unlike nuclear cataract, progression is intermittent, stepwise and non-uniform.

  16. Aging across the tree of life: The importance of a comparative perspective for the use of animal models in aging.

    PubMed

    Cohen, Alan A

    2017-07-06

    Use of model organisms in aging research is problematic because our ability to extrapolate across the tree of life is not clear. On one hand, there are conserved pathways that regulate lifespan in organisms including yeast, nematodes, fruit flies, and mice. On the other, many intermediate taxa across the tree of life appear not to age at all, and there is substantial variation in aging mechanisms and patterns, sometimes even between closely related species. There are good evolutionary and mechanistic reasons to expect this complexity, but it means that model organisms must be used with caution and that results must always be interpreted through a broader comparative framework. Additionally, it is essential to include research on non-traditional and unusual species, and to integrate mechanistic and demographic research. There will be no simple answers regarding the biology of aging, and research approaches should reflect this. This article is part of a Special Issue entitled: Animal models of aging - edited by Houtkooper Riekelt. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. 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.

  18. 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

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

    PubMed

    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.

  20. Applying the age-shift approach to model responses to midrotation fertilization

    Treesearch

    Colleen A. Carlson; Thomas R. Fox; H. Lee Allen; Timothy J. Albaugh

    2010-01-01

    Growth and yield models used to evaluate midrotation fertilization economics require adjustments to account for the typically observed responses. This study investigated the use of age-shift models to predict midrotation fertilizer responses. Age-shift prediction models were constructed from a regional study consisting of 43 installations of a nitrogen (N) by...

  1. GDF11 administration does not extend lifespan in a mouse model of premature aging

    PubMed Central

    Freitas-Rodríguez, Sandra; Rodríguez, Francisco; Folgueras, Alicia R.

    2016-01-01

    GDF11 has recently emerged as a powerful anti-aging candidate, found in young blood, capable of rejuvenating a number of aged tissues, such as heart, skeletal muscle and brain. However, recent reports have shown contradictory data questioning its capacity to reverse age-related tissue dysfunction. The availability of a mouse model of accelerated aging, which shares most of the features occurring in physiological aging, gives us an excellent opportunity to test in vivo therapies aimed at extending lifespan both in pathological and normal aging. On this basis, we wondered whether the proposed anti-aging functions of GDF11 would have an overall effect on longevity. We first confirmed the existence of a reduction in GDF11/8 levels in our mouse model of accelerated aging compared with wild-type littermates. However, we show herein that GDF11 daily administration does not extend lifespan of premature-aged mice. PMID:27507054

  2. 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…

  3. 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)

  4. 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.

  5. Autophagy drives epidermal deterioration in a Drosophila model of tissue aging.

    PubMed

    Scherfer, Christoph; Han, Violet C; Wang, Yan; Anderson, Aimee E; Galko, Michael J

    2013-04-01

    Organismal lifespan has been the primary readout in aging research. However, how longevity genes control tissue-specific aging remains an open question. To examine the crosstalk between longevity programs and specific tissues during aging, biomarkers of organ-specific aging are urgently needed. Since the earliest signs of aging occur in the skin, we sought to examine skin aging in a genetically tractable model. Here we introduce a Drosophila model of skin aging. The epidermis undergoes a dramatic morphological deterioration with age that includes membrane and nuclear loss. These changes were decelerated in a long-lived mutant and accelerated in a short-lived mutant. An increase in autophagy markers correlated with epidermal aging. Finally, the epidermis of Atg7 mutants retained younger characteristics, suggesting that autophagy is a critical driver of epidermal aging. This is surprising given that autophagy is generally viewed as protective during aging. Since Atg7 mutants are short-lived, the deceleration of epidermal aging in this mutant suggests that in the epidermis healthspan can be uncoupled from longevity. Because the aging readout we introduce here has an early onset and is easily visualized, genetic dissection using our model should identify other novel mechanisms by which lifespan genes feed into tissue-specific aging.

  6. Leaching of BTEX from Aged Crude Oil Contaminated Model Soils: Experimental and Modeling Results

    SciTech Connect

    Huesemann, Michael H.; Hausmann, Tom S.; Fortman, Timothy J.

    2005-01-01

    It is generally assumed that soil properties such as organic matter content, porosity, and mineral surface area have a significant effect on the bioavailability and leachability of aged petroleum hydrocarbons. In order to test this hypothesis, nine model soils or sorbents (i.e., fine and coarse quartz sand, montmorillonite and kaolinite clay, peat, 60? and 150? silica gel, a loam soil, and non-porous glass beads) were spiked with a crude oil, aged for 27 months in the laboratory, and transferred to glass columns for the performance of continuous flow leaching experiments. The column effluents were periodically sampled for 43 days and analyzed for BTEX. A one-dimensional flow model for predicting the dissolution and dispersion of individual hydrocarbons from a multi-component NAPL such as crude oil was used to fit the leaching data (i.e., the BTEX concentration versus time curves) by adjusting the equilibrium oil-leachate partitioning coefficient (Kol) for each respective hydrocarbon. The Peclet number, which is a measure of dispersion and a required modeling parameter, was measured in separate chloride tracer experiments for each soil column. Results demonstrate that soil properties did not significantly affect the leaching kinetics of BTEX from the columns. Instead, BTEX leaching curves could be successfully fitted with the one-dimensional NAPL dissolution flow model for all sorbents with the exception of montmorillonite clay. The fitting parameter Kol for each hydrocarbon was found to be similar to the Kol values that were independently measured for the same crude oil by Rixey et al. (Journal of Hazardous Materials B, 65: 137-156, 1999). In addition, the fitted Kol values were very similar for BTEX leaching from aged compared to freshly spiked loam soil. These findings indicate that leaching of BTEX in the aged soils that are contaminated with crude oil at the high concentrations commonly found in the environment (i.e., >20,000 mg/kg) was not affected by soil

  7. Building from a conceptual model of the resilience process during ageing, towards the Groningen Aging Resilience Inventory.

    PubMed

    van Abbema, Renske; Bielderman, Annemiek; De Greef, Mathieu; Hobbelen, Hans; Krijnen, Wim; van der Schans, Cees

    2015-09-01

    To develop and psychometrically test the Groningen Ageing Resilience Inventory. Ageing is a process that is often accompanied by functional limitation, disabilities and losses. Instead of focusing on these negative events of ageing, there are opportunities in focusing on adaptation mechanisms, like resilience, that are helpful to cope with those adversities. Cross-sectional study. The study was conducted from 2011-2012. First, a conceptual model of resilience during the ageing process was constructed. Next, items were formulated that made up a comprehensive template questionnaire reflecting the model. Finally, a cross-sectional study was performed to evaluate the construct validity and internal consistency of this template 16-item questionnaire. Participants (N = 229) with a mean age of 71·5 years, completed the template 16-item Groningen Ageing Resilience Inventory, and performance based tests and psychological questionnaires. Exploratory factor analysis resulted in a two factor solution of internal and external resources of resilience. Three items did not discriminate well between the two factors and were deleted, remaining a final 13-item questionnaire that shows evidence of good internal consistency. The direction and magnitude of the correlations with other measures support the construct validity. The Groningen Ageing Resilience Inventory is a useful instrument that can help nurses, other healthcare workers, researchers and providers of informal care to identify the internal and external resources of resilience in individuals and groups. In a multidisciplinary biopsychosocial approach this knowledge provides tools for empowering older patients in performing health promoting behaviors and self-care tasks. © 2015 John Wiley & Sons Ltd.

  8. Rb-Sr age of a Luna 16 basalt and the model age of lunar soils.

    NASA Technical Reports Server (NTRS)

    Papanastassiou, D. A.; Wasserburg, G. J.

    1972-01-01

    An internal isochron was determined on a small basalt fragment (sample B-1) returned from the Luna 16 mission, which yields an age of 3.42 plus or minus 0.8 b.y. and a low initial Sr87/Sr86 value. A comparison is made of the data from four lunar missions to mare sites which shows that the last period of major flooding of the mare basins is confined to a narrow time interval of only 0.55 b.y. The direct evidence of major lunar magmatic activity appears to be confined to the interval from 3.1 to 4.0 b.y. The Sr87/Sr86 values for all mare basalts are extremely primitive and lie in a rather narrow range. A diagram is given for initial Sr87/Sr86 as a function of time for all lunar rocks.

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

    PubMed

    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 muscular

  10. Age problem in the holographic dark energy model

    SciTech Connect

    Wei Hao; Zhang Shuangnan

    2007-09-15

    In this paper, we test the original holographic dark energy model with some old high redshift objects. The main idea is very simple: the universe cannot be younger than its constituents. We find that the original holographic dark energy model can be ruled out, unless a lower Hubble constant is taken.

  11. Optimality models in the age of experimental evolution and genomics

    PubMed Central

    Bull, J. J.; Wang, I.-N.

    2010-01-01

    Optimality models have been used to predict evolution of many properties of organisms. They typically neglect genetic details, whether by necessity or design. This omission is a common source of criticism, and although this limitation of optimality is widely acknowledged, it has mostly been defended rather than evaluated for its impact. Experimental adaptation of model organisms provides a new arena for testing optimality models and for simultaneously integrating genetics. First, an experimental context with a well-researched organism allows dissection of the evolutionary process to identify causes of model failure – whether the model is wrong about genetics or selection. Second, optimality models provide a meaningful context for the process and mechanics of evolution, and thus may be used to elicit realistic genetic bases of adaptation – an especially useful augmentation to well-researched genetic systems. A few studies of microbes have begun to pioneer this new direction. Incompatibility between the assumed and actual genetics has been demonstrated to be the cause of model failure in some cases. More interestingly, evolution at the phenotypic level has sometimes matched prediction even though the adaptive mutations defy mechanisms established by decades of classic genetic studies. Integration of experimental evolutionary tests with genetics heralds a new wave for optimality models and their extensions that does not merely emphasize the forces driving evolution. PMID:20646132

  12. Aging stem cells. A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging.

    PubMed

    Zhang, Weiqi; Li, Jingyi; Suzuki, Keiichiro; Qu, Jing; Wang, Ping; Zhou, Junzhi; Liu, Xiaomeng; Ren, Ruotong; Xu, Xiuling; Ocampo, Alejandro; Yuan, Tingting; Yang, Jiping; Li, Ying; Shi, Liang; Guan, Dee; Pan, Huize; Duan, Shunlei; Ding, Zhichao; Li, Mo; Yi, Fei; Bai, Ruijun; Wang, Yayu; Chen, Chang; Yang, Fuquan; Li, Xiaoyu; Wang, Zimei; Aizawa, Emi; Goebl, April; Soligalla, Rupa Devi; Reddy, Pradeep; Esteban, Concepcion Rodriguez; Tang, Fuchou; Liu, Guang-Hui; Belmonte, Juan Carlos Izpisua

    2015-06-05

    Werner syndrome (WS) is a premature aging disorder caused by WRN protein deficiency. Here, we report on the generation of a human WS model in human embryonic stem cells (ESCs). Differentiation of WRN-null ESCs to mesenchymal stem cells (MSCs) recapitulates features of premature cellular aging, a global loss of H3K9me3, and changes in heterochromatin architecture. We show that WRN associates with heterochromatin proteins SUV39H1 and HP1α and nuclear lamina-heterochromatin anchoring protein LAP2β. Targeted knock-in of catalytically inactive SUV39H1 in wild-type MSCs recapitulates accelerated cellular senescence, resembling WRN-deficient MSCs. Moreover, decrease in WRN and heterochromatin marks are detected in MSCs from older individuals. Our observations uncover a role for WRN in maintaining heterochromatin stability and highlight heterochromatin disorganization as a potential determinant of human aging. Copyright © 2015, American Association for the Advancement of Science.

  13. 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.

  14. Preparing the workforce for healthy aging programs: the Skills for Healthy Aging Resources and Programs (SHARP) model.

    PubMed

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

    2014-10-01

    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 and test a model community college career technical education program, Skills for Healthy Aging Resources and Programs (SHARP), for undergraduate college students, current personnel in aging service and community organizations, and others interested in retraining. A multidisciplinary cross-sector team from disciplines of public health, sociology, gerontology and nursing developed four competency-based courses that focus on healthy aging, behavior change strategies, program management, an internship, and an option for leader training in the Chronic Disease Self-Management Program. To enhance implementation and fidelity, intensive faculty development training was provided to all instructors and community agency partners. Baseline and postprogram evaluation of competencies for faculty and students was conducted. Process evaluation for both groups focused on satisfaction with the curricula and suggestions for program improvement. SHARP has been piloted five times at two community colleges. Trainees (n = 113) were primarily community college students (n = 108) and current aging service personnel (n = 5). Statistically significant improvements in all competencies were found for both faculty and students. Process evaluation outcomes identified the needed logical and component adaptations to enhance the feasibility of program implementation, dissemination, and student satisfaction. The SHARP program provides a well-tested, evidence-based effective model for addressing workforce preparation in support of healthy aging service program expansion and delivery.

  15. The use of urinary proteomics in the assessment of suitability of mouse models for ageing

    PubMed Central

    Nkuipou-Kenfack, Esther; Schanstra, Joost P.; Bajwa, Seerat; Pejchinovski, Martin; Vinel, Claire; Dray, Cédric; Valet, Philippe; Bascands, Jean-Loup; Vlahou, Antonia; Koeck, Thomas; Borries, Melanie; Busch, Hauke; Bechtel-Walz, Wibke; Huber, Tobias B.; Rudolph, Karl L.; Pich, Andreas; Mischak, Harald; Zürbig, Petra

    2017-01-01

    Ageing is a complex process characterised by a systemic and progressive deterioration of biological functions. As ageing is associated with an increased prevalence of age-related chronic disorders, understanding its underlying molecular mechanisms can pave the way for therapeutic interventions and managing complications. Animal models such as mice are commonly used in ageing research as they have a shorter lifespan in comparison to humans and are also genetically close to humans. To assess the translatability of mouse ageing to human ageing, the urinary proteome in 89 wild-type (C57BL/6) mice aged between 8–96 weeks was investigated using capillary electrophoresis coupled to mass spectrometry (CE-MS). Using age as a continuous variable, 295 peptides significantly correlated with age in mice were identified. To investigate the relevance of using mouse models in human ageing studies, a comparison was performed with a previous correlation analysis using 1227 healthy subjects. In mice and humans, a decrease in urinary excretion of fibrillar collagens and an increase of uromodulin fragments was observed with advanced age. Of the 295 peptides correlating with age, 49 had a strong homology to the respective human age-related peptides. These ortholog peptides including several collagen (N = 44) and uromodulin (N = 5) fragments were used to generate an ageing classifier that was able to discriminate the age among both wild-type mice and healthy subjects. Additionally, the ageing classifier depicted that telomerase knock-out mice were older than their chronological age. Hence, with a focus on ortholog urinary peptides mouse ageing can be translated to human ageing. PMID:28199320

  16. The use of urinary proteomics in the assessment of suitability of mouse models for ageing.

    PubMed

    Nkuipou-Kenfack, Esther; Schanstra, Joost P; Bajwa, Seerat; Pejchinovski, Martin; Vinel, Claire; Dray, Cédric; Valet, Philippe; Bascands, Jean-Loup; Vlahou, Antonia; Koeck, Thomas; Borries, Melanie; Busch, Hauke; Bechtel-Walz, Wibke; Huber, Tobias B; Rudolph, Karl L; Pich, Andreas; Mischak, Harald; Zürbig, Petra

    2017-01-01

    Ageing is a complex process characterised by a systemic and progressive deterioration of biological functions. As ageing is associated with an increased prevalence of age-related chronic disorders, understanding its underlying molecular mechanisms can pave the way for therapeutic interventions and managing complications. Animal models such as mice are commonly used in ageing research as they have a shorter lifespan in comparison to humans and are also genetically close to humans. To assess the translatability of mouse ageing to human ageing, the urinary proteome in 89 wild-type (C57BL/6) mice aged between 8-96 weeks was investigated using capillary electrophoresis coupled to mass spectrometry (CE-MS). Using age as a continuous variable, 295 peptides significantly correlated with age in mice were identified. To investigate the relevance of using mouse models in human ageing studies, a comparison was performed with a previous correlation analysis using 1227 healthy subjects. In mice and humans, a decrease in urinary excretion of fibrillar collagens and an increase of uromodulin fragments was observed with advanced age. Of the 295 peptides correlating with age, 49 had a strong homology to the respective human age-related peptides. These ortholog peptides including several collagen (N = 44) and uromodulin (N = 5) fragments were used to generate an ageing classifier that was able to discriminate the age among both wild-type mice and healthy subjects. Additionally, the ageing classifier depicted that telomerase knock-out mice were older than their chronological age. Hence, with a focus on ortholog urinary peptides mouse ageing can be translated to human ageing.

  17. The development of a ductility-based aging model for low temperature aged U-6Nb alloy

    SciTech Connect

    Bridges, B

    2005-03-24

    This study focuses on the ductility evaluation of low-temperature (100 and 200 C) aged U-6Nb alloy. The objective is to develop a ductility-based aging model to improve lifetime prediction for weapon components in the stockpile environment. Literature review shows that the work hardening n-value and the strain-rate hardening mvalue are the two most important metallurgical factors for the uniform and the post-uniform (necking) ductility control, respectively. Unfortunately, both n and m values of the U-6Nb alloy are lacking. The study shows that the total ductility of U-6Nb is dominated by the uniform ductility, which deteriorates in both 100 C and 200 C aging. Further analysis shows that the uniform ductility correlates well with the work hardening n-value of the later stage deformation in which dislocation-slip is the mechanism. The kinetics of the loss of uniform ductility and the associated reduction in work-hardening n-value in low temperature aging will be used for the development of a ductility-based aging model. The necking ductility appears to be a minor but significant factor in the total ductility of U-6Nb. It does not show a clear trend due to large data scatter. The uncertain nature of necking failure may always hinder a reliable measurement of necking ductility. Consequently, a precise measurement of strain-rate hardening m-value could be a viable alternative to model the metallurgical contribution to the necking ductility. The conventional strain rate step-change method and the ABI (Automated-Ball-Indentation) test both show promising result in m-value measurement.

  18. 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.

  19. Computational models in the age of large datasets.

    PubMed

    O'Leary, Timothy; Sutton, Alexander C; Marder, Eve

    2015-06-01

    Technological advances in experimental neuroscience are generating vast quantities of data, from the dynamics of single molecules to the structure and activity patterns of large networks of neurons. How do we make sense of these voluminous, complex, disparate and often incomplete data? How do we find general principles in the morass of detail? Computational models are invaluable and necessary in this task and yield insights that cannot otherwise be obtained. However, building and interpreting good computational models is a substantial challenge, especially so in the era of large datasets. Fitting detailed models to experimental data is difficult and often requires onerous assumptions, while more loosely constrained conceptual models that explore broad hypotheses and principles can yield more useful insights. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Modeling of lithium plating induced aging of lithium-ion batteries: Transition from linear to nonlinear aging

    NASA Astrophysics Data System (ADS)

    Yang, Xiao-Guang; Leng, Yongjun; Zhang, Guangsheng; Ge, Shanhai; Wang, Chao-Yang

    2017-08-01

    A physics-based Li-ion battery (LIB) aging model accounting for both lithium plating and solid electrolyte interphase (SEI) growth is presented, and is applied to study the aging behavior of a cell undergoing prolonged cycling at moderate operating conditions. Cell aging is found to be linear in the early stage of cycling but highly nonlinear in the end with rapid capacity drop and resistance rise. The linear aging stage is found to be dominated by SEI growth, while the transition from linear to nonlinear aging is attributed to the sharp rise of lithium plating rate. Lithium plating starts to occur in a narrow portion of the anode near the separator after a certain number of cycles. The onset of lithium plating is attributed to the drop of anode porosity associated with SEI growth, which aggravates the local electrolyte potential gradient in the anode. The presence of lithium metal accelerates the porosity reduction, further promoting lithium plating. This positive feedback leads to exponential increase of lithium plating rate in the late stage of cycling, as well as local pore clogging near the anode/separator interface which in turn leads to a sharp resistance rise.

  1. 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

  2. Budding yeast as a model organism to study the effects of age.

    PubMed

    Denoth Lippuner, Annina; Julou, Thomas; Barral, Yves

    2014-03-01

    Although a budding yeast culture can be propagated eternally, individual yeast cells age and eventually die. The detailed knowledge of this unicellular eukaryotic species as well as the powerful tools developed to study its physiology makes budding yeast an ideal model organism to study the mechanisms involved in aging. Considering both detrimental and positive aspects of age, we review changes occurring during aging both at the whole-cell level and at the intracellular level. The possible mechanisms allowing old cells to produce rejuvenated progeny are described in terms of accumulation and inheritance of aging factors. Based on the dynamic changes associated with age, we distinguish different stages of age: early age, during which changes do not impair cell growth; intermediate age, during which aging factors start to accumulate; and late age, which corresponds to the last divisions before death. For each aging factor, we examine its asymmetric segregation and whether it plays a causal role in aging. Using the example of caloric restriction, we describe how the aging process can be modulated at different levels and how changes in different organelles might interplay with each other. Finally, we discuss the beneficial aspects that might be associated with age.

  3. 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

  4. 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.

  5. 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

  6. User Manual for Personnel Inventory Aging and Promotion Model

    DTIC Science & Technology

    2009-06-01

    11 Controller form...................................................................12 Increase Decrease Personnel Form...closed. 11 Controller form Figure 3. Controller form When the model opens, the Controller form auto- matically opens. The form has...current date and time is the cur- rent time. 11 This results in one Excel file for each run. Note: The driver opens and creates literally

  7. [The senescence-accelerated oxys rats--a genetic model of premature aging and age-dependent degenerative diseases].

    PubMed

    Kolosova, N G; Stefanova, N A; Korbolina, E E; Fursova, A Zh; Kozhevnikova, O S

    2014-01-01

    The genetic model of accelerated senescence and the associated diseases--the OXYS strain of rats--was created using selection and inbreeding of Wistar rats sensitive to cataractogenic effects of galactose. In the first 5 generations, the development of cataract was induced by galactose overconsumption, and after that, the rats were selected for early spontaneous cataract. Genetically linked with the latter was a set of features of accelerated senescence, which were inherited by the subsequent generations of the animals. At present, we have a 103rd generation of OXYS rats, who at young age develop retinopathy (similar to age-related macular degeneration in humans), osteoporosis, arterial hypertension, accelerated thymus involution, sarcopenia, and neurodegenerative changes in the brain (with the features characteristic of Alzheimer's disease), besides the cataract. This review discusses possible mechanisms of the accelerated senescence: the results of comparison of retinal transcriptomes between OXYS and Wistar(control) rats at different ages, studies of the markers of Alzheimer's disease in the retina and in certain brain regions, and the outcome of the efforts to develop congenic strains of animals via a transfer of several quantitative trait loci (QTLs) of chromosome 1 from OXYS to WAG rats that are associated with the signs of accelerated senescence. The uniqueness of OXYS rats lies in the complex composition of manifestations of the traits; accordingly, this rat model can be used not only for studies of the mechanisms of aging and pathogenesis of the age-related diseases but also for objective evaluation of new methods of treatment and prevention.

  8. Age- and sex-specific thorax finite element model development and simulation.

    PubMed

    Schoell, Samantha L; Weaver, Ashley A; Vavalle, Nicholas A; Stitzel, Joel D

    2015-01-01

    The shape, size, bone density, and cortical thickness of the thoracic skeleton vary significantly with age and sex, which can affect the injury tolerance, especially in at-risk populations such as the elderly. Computational modeling has emerged as a powerful and versatile tool to assess injury risk. However, current computational models only represent certain ages and sexes in the population. The purpose of this study was to morph an existing finite element (FE) model of the thorax to depict thorax morphology for males and females of ages 30 and 70 years old (YO) and to investigate the effect on injury risk. Age- and sex-specific FE models were developed using thin-plate spline interpolation. In order to execute the thin-plate spline interpolation, homologous landmarks on the reference, target, and FE model are required. An image segmentation and registration algorithm was used to collect homologous rib and sternum landmark data from males and females aged 0-100 years. The Generalized Procrustes Analysis was applied to the homologous landmark data to quantify age- and sex-specific isolated shape changes in the thorax. The Global Human Body Models Consortium (GHBMC) 50th percentile male occupant model was morphed to create age- and sex-specific thoracic shape change models (scaled to a 50th percentile male size). To evaluate the thoracic response, 2 loading cases (frontal hub impact and lateral impact) were simulated to assess the importance of geometric and material property changes with age and sex. Due to the geometric and material property changes with age and sex, there were observed differences in the response of the thorax in both the frontal and lateral impacts. Material property changes alone had little to no effect on the maximum thoracic force or the maximum percent compression. With age, the thorax becomes stiffer due to superior rotation of the ribs, which can result in increased bone strain that can increase the risk of fracture. For the 70-YO models

  9. From cradle to grave: high-throughput studies of aging in model organisms.

    PubMed

    Spivey, Eric C; Finkelstein, Ilya J

    2014-07-01

    Aging-the progressive decline of biological functions-is a universal fact of life. Decades of intense research in unicellular and metazoan model organisms have highlighted that aging manifests at all levels of biological organization - from the decline of individual cells, to tissue and organism degeneration. To better understand the aging process, we must first aim to integrate quantitative biological understanding on the systems and cellular levels. A second key challenge is to then understand the many heterogeneous outcomes that may result in aging cells, and to connect cellular aging to organism-wide degeneration. Addressing these challenges requires the development of high-throughput aging and longevity assays. In this review, we highlight the emergence of high-throughput aging approaches in the most commonly used model organisms. We conclude with a discussion of the critical questions that can be addressed with these new methods.

  10. Education and Successful Aging Trajectories: A Longitudinal Population-Based Latent Variable Modelling Analysis.

    PubMed

    Cosco, Theodore D; Stephan, Blossom C M; Brayne, Carol; Muniz, Graciela

    2017-10-11

    As the population ages, interest is increasing in studying aging well. However, more refined means of examining predictors of biopsychosocial conceptualizations of successful aging (SA) are required. Existing evidence of the relationship between early-life education and later-life SA is unclear. The Successful Aging Index (SAI) was mapped onto the Cognitive Function and Aging Study (CFAS), a longitudinal population-based cohort (n = 1,141). SAI scores were examined using growth mixture modelling (GMM) to identify SA trajectories. Unadjusted and adjusted (age, sex, occupational status) ordinal logistic regressions were conducted to examine the association between trajectory membership and education level. GMM identified a three-class model, capturing high, moderate, and low functioning trajectories. Adjusted ordinal logistic regression models indicated that individuals in higher SAI classes were significantly more likely to have higher educational attainment than individuals in the lower SAI classes. These results provide evidence of a life course link between education and SA.

  11. Mini-Review: Retarding Aging in Murine Genetic Models of Neurodegeneration

    PubMed Central

    Albin, Roger L.; Miller, Richard A.

    2015-01-01

    Retardation of aging processes is a plausible approach to delaying the onset or slowing the progression of common neurodegenerative disorders. We review the results of experiments using murine genetic models of Alzheimer disease and Huntington disease to evaluate the effects of retarding aging. While positive results are reported in several of these experiments, there are several discrepancies in behavioral and pathologic outcomes both within and between different experiments. Similarly, different experiments yield varying assessments of potential proximate mechanisms of action of retarding aging. The anti-aging interventions used for some experiments include some that show only modest effects on lifespan, and others that have proven hard to reproduce. Several experiments used aggressive transgenic neurodegenerative disease models that may be less relevant in the context of age-related diseases. The experience with these models and interventions may be useful in designing future experiments assessing anti-aging interventions for disease-modifying treatment of neurodegenerative diseases. PMID:26477301

  12. The logistic, two-sex, age-structured population model.

    PubMed

    Yang, Kai; Milner, Fabio

    2009-03-01

    In this paper, we introduce the logistic effect into the two-sex population model introduced by Hoppensteadt. We address the problem of existence and uniqueness of continuous and classical solutions. We first give sufficient conditions for a unique continuous solution to exist locally and also globally. Next, the existence of classical solutions is established under some mild assumptions on the vital rates. Finally, we study the existence of equilibria and give an upper bound for the total population at steady state.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. Aging and symptoms of anxiety and depression: structural invariance of the tripartite model.

    PubMed

    Teachman, Bethany A; Siedlecki, Karen L; Magee, Joshua C

    2007-03-01

    Negative affect measures were evaluated in a cross-sectional community sample of adults aged 18-93 (N = 335) to examine the structure of neuroticism, anxiety, and depressive symptoms in young, middle, and older adult cohorts. Structural equation modeling was used to contrast 3 nested models: a 1-factor general distress model; a 2-factor high negative-low positive affect model; and a 3-factor "tripartite model" reflecting a higher order Negative Affect factor that is common to depression and anxiety problems and 2 lower order factors, Low Positive Affect (mostly specific to depression) and Arousal (specific to anxiety/panic). As expected, the tripartite model fit best for all age groups. Further, multigroup analyses indicated age invariance for the tripartite model, suggesting the model can be effectively applied with older populations.

  18. 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

  19. Applicability of Willems model for dental age estimations in Brazilian children.

    PubMed

    Franco, Ademir; Thevissen, Patrick; Fieuws, Steffen; Souza, Paulo Henrique Couto; Willems, Guy

    2013-09-10

    Several studies described tooth development as a reliable pathway for age estimations. Depending on the considered life span, the dental age indicators vary. In children, combinations of developing teeth provide the best information about age. In sub adults third molar mineralization is almost exclusively considered. The aim of this study was, firstly, to verify the Willems model in a Brazilian sample. Secondly, to observe differences between the Willems model and a new developed Brazilian model. Thirdly, the information of permanent teeth (PM) and third molar (TM), development was combined for age estimation in children. A sample of 1357 panoramic radiographs of Brazilian males (M) and females (F), with age between 5 and 23 years was collected. The technique of Gleiser and Hunt modified by Kohler (1955) [34] was applied for third molar staging in the entire sample. The Demirjian staging technique was used on the mandibular left permanent teeth (except third molars) of all individuals from 5 to 15 years. Kappa and weighted Kappa statistics were performed to verify inter- and intra-observer reliabilities. Based on the obtained Demirjian scores the Willems model was verified. Next the data were split to develop a new Brazilian model based on the Willems method and to verify the established model. The accuracy in age prediction between the Willems model and the new Brazilian model was compared. Additionally, regression models including PM, TM and PM plus TM information were compared. The Kappa and weighted Kappa statistics revealed high agreement between observers (0.88 Kappa; 0.93 weighted Kappa). The differences between predicted and chronological age for the verified Willems model were expressed in mean errors of -0.17 and -0.38 year for F and M respectively. The differences in mean error between the new developed Brazilian model and the Willems model were 0.02 (F) and 0.20 (M) year. The regression models combining PT and TM information provided only in the age

  20. The companion dog as a unique translational model for aging.

    PubMed

    Mazzatenta, Andrea; Carluccio, Augusto; Robbe, Domenico; Giulio, Camillo Di; Cellerino, Alessandro

    2017-10-01

    The dog is a unique species due to its wide variation among breeds in terms of size, morphology, behaviour and lifespan, coupled with a genetic structure that facilitates the dissection of the genetic architecture that controls these traits. Dogs and humans co-evolved and share recent evolutionary selection processes, such as adaptation to digest starch-rich diets. Many diseases of the dog have a human counterpart, and notably Alzheimer's disease, which is otherwise difficult to model in other organisms. Unlike laboratory animals, companion dogs share the human environment and lifestyle, are exposed to the same pollutants, and are faced with pathogens and infections. Dogs represented a very useful model to understand the relationship between size, insulin-like growth factor-1 genetic variation and lifespan, and have been used to test the effects of dietary restriction and immunotherapy for Alzheimer's disease. Very recently, rapamycin was tested in companion dogs outside the laboratory, and this approach where citizens are involved in research aimed at the benefit of dog welfare might become a game changer in geroscience. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. 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.

  2. Age-dependent Fourier model of the shape of the isolated ex vivo human crystalline lens

    PubMed Central

    Urs, Raksha; Ho, Arthur; Manns, Fabrice; Parel, Jean-Marie

    2010-01-01

    Purpose To develop an age-dependent mathematical model of the zero-order shape of the isolated ex vivo human crystalline lens, using one mathematical function, that can be subsequently used to facilitate the development of other models for specific purposes such as optical modeling and analytical and numerical modeling of the lens. Methods Profiles of whole isolated human lenses (n=30) aged 20 to 69, were measured from shadow-photogrammetric images. The profiles were fit to a 10th-order Fourier series consisting of cosine functions in polar-coordinate system that included terms for tilt and decentration. The profiles were corrected using these terms and processed in two ways. In the first, each lens was fit to a 10th-order Fourier series to obtain thickness and diameter, while in the second, all lenses were simultaneously fit to a Fourier series equation that explicitly include linear terms for age to develop an age-dependent mathematical model for the whole lens shape. Results Thickness and diameter obtained from Fourier series fits exhibited high correlation with manual measurements made from shadow-photogrammetric images. The root-mean-squared-error of the age-dependent fit was 205 μm. The age-dependent equations provide a reliable lens model for ages 20 to 60 years. Conclusion The contour of the whole human crystalline lens can be modeled with a Fourier series. Shape obtained from the age-dependent model described in this paper can be used to facilitate the development of other models for specific purposes such as optical modeling and analytical and numerical modeling of the lens. PMID:20338192

  3. 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.

  4. 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

  5. Aging-like skin changes induced by ultraviolet irradiation in an animal model of metabolic syndrome.

    PubMed

    Akase, Tomoko; Nagase, Takashi; Huang, Lijuan; Ibuki, Ai; Minematsu, Takeo; Nakagami, Gojiro; Ohta, Yasunori; Shimada, Tsutomu; Aburada, Masaki; Sugama, Junko; Sanada, Hiromi

    2012-04-01

    Both physiological skin aging and pathologic photo-aging caused by ultraviolet (UV) irradiation are mediated by latent inflammation and oxidative stress. Although numerous animal skin-aging models have used UV irradiation, most require massive doses or long-term irradiation. To establish a more refined skin-aging model, we focused on an animal model of metabolic syndrome (MS) because MS involves damage to various organs via oxidative stress or inflammation, similar to the changes associated with aging. We hypothesized that MS skin might exhibit more aging-like changes after milder, shorter-term UV irradiation than would normal animal skin under similar conditions, thus providing a useful model for skin aging. The authors therefore examined the skin from Tsumura Suzuki obese diabetic (TSOD) mice (MS model) and control Tsumura Suzuki non-obese (TSNO) mice before and after UV irradiation. Skin from TSOD mice had a thinner epidermis and dermis, a thicker fatty layer, reduced density and convolution of the fragmented collagen fibers, and upregulated expression of tumor necrosis factor (TNF)-α, a dual marker for inflammation and aging, compared to the skin from TSNO mice. UV irradiation affected TSOD skin more severely than TSNO skin, resulting in various changes resembling those in aged human skin, including damage to the dermis and subcutaneous fatty tissue, infiltration of inflammatory cells, and further upregulation of TNF-α expression. These results suggest that UV-irradiated TSOD mice may provide a new model of skin aging and imply that skin from humans with MS is more susceptible to UV- or aging-related damage than normal human skin.

  6. Ages and transit times as important diagnostics of model performance for predicting C allocation in ecosystem models

    NASA Astrophysics Data System (ADS)

    Ceballos-Núñez, Verónika; Richardson, Andrew; Sierra, Carlos

    2017-04-01

    The global carbon cycle is strongly controlled by the source/sink strength of vegetation as well as the capacity of terrestrial ecosystems to retain this carbon. However, it is uncertain how some vegetation dynamics such as the allocation of carbon to different ecosystem compartments should be represented in models. The assumptions behind model structures may result in highly divergent model predictions. Here, we asses model performance by calculating the age of the carbon in the system and in each compartment, and the overall transit time of C in the system. We used these diagnostics to assess the influence of three different carbon allocation schemes on the rates of C cycling in vegetation. First, we used published measurements of ecosystem C compartments from the Harvard Forest Environmental Measurement Site to find the best set of parameters for the different model structures. Second, we calculated C stocks, respiration fluxes, radiocarbon values, ages, and transit times. We found a good fit of the three model structures to the available data, but the time series of C in foliage and wood need to be complemented with other ecosystem compartments in order to reduce the high parameter collinearity that we observed and reduce model equifinality. Differences in model structures had a small impact on predicting ecosystem C compartments, but overall they resulted in very different predictions of age and transit time distributions. In particular, the inclusion of a storage compartment had an important impact on predicting system ages and transit times. In the case of the models with 1 or 2 storage compartments, the age of carbon in the system and in each of the compartments was distributed more towards younger ages than in the model that had no storage; the mean system age of these two models with storage was 80 years younger than in the model without storage. As expected from these age distributions, the mean transit time for the two models with storage compartments

  7. Aging and immortality in a cell proliferation model.

    PubMed

    Antal, T; Blagoev, K B; Trugman, S A; Redner, S

    2007-10-07

    We investigate a model of cell division in which the length of telomeres within a cell regulates its proliferative potential. At each division, telomeres undergo a systematic length decrease as well as a superimposed fluctuation due to exchange of telomere DNA between the two daughter cells. A cell becomes senescent when one or more of its telomeres become shorter than a critical length. We map this telomere dynamics onto a biased branching-diffusion process with an absorbing boundary condition whenever any telomere reaches the critical length. Using first-passage ideas, we find a phase transition between finite lifetime and immortality (infinite proliferation) of the cell population as a function of the influence of telomere shortening, fluctuations, and cell division.

  8. 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

  9. The importance of age-related decline in forest NPP for modeling regional carbon balances.

    PubMed

    Zaehle, Sönke; Sitch, Stephen; Prentice, I Colin; Liski, Jari; Cramer, Wolfgang; Erhard, Markus; Hickler, Thomas; Smith, Benjamin

    2006-08-01

    We show the implications of the commonly observed age-related decline in aboveground productivity of forests, and hence forest age structure, on the carbon dynamics of European forests in response to historical changes in environmental conditions. Size-dependent carbon allocation in trees to counteract increasing hydraulic resistance with tree height has been hypothesized to be responsible for this decline. Incorporated into a global terrestrial biosphere model (the Lund-Potsdam-Jena model, LPJ), this hypothesis improves the simulated increase in biomass with stand age. Application of the advanced model, including a generic representation of forest management in even-aged stands, for 77 European provinces shows that model-based estimates of biomass development with age compare favorably with inventory-based estimates for different tree species. Model estimates of biomass densities on province and country levels, and trends in growth increment along an annual mean temperature gradient are in broad agreement with inventory data. However, the level of agreement between modeled and inventory-based estimates varies markedly between countries and provinces. The model is able to reproduce the present-day age structure of forests and the ratio of biomass removals to increment on a European scale based on observed changes in climate, atmospheric CO2 concentration, forest area, and wood demand between 1948 and 2000. Vegetation in European forests is modeled to sequester carbon at a rate of 100 Tg C/yr, which corresponds well to forest inventory-based estimates.

  10. Aging and linear response in the Hébraud–Lequeux model for amorphous rheology

    NASA Astrophysics Data System (ADS)

    Sollich, Peter; Olivier, Julien; Bresch, Didier

    2017-04-01

    We analyse the aging dynamics of the Hébraud–Lequeux model, a self-consistent stochastic model for the evolution of local stress in an amorphous material. We show that the model exhibits initial-condition dependent freezing: the stress diffusion constant decays with time as D∼ 1/{{t}2} during aging so that the cumulative amount of memory that can be erased, which is given by the time integral of D(t), is finite. Accordingly the shear stress relaxation function, which we determine in the long-time regime, only decays to a plateau and becomes progressively elastic as the system ages. The frequency-dependent shear modulus exhibits a corresponding overall decay of the dissipative part with system age, while the characteristic relaxation times scale linearly with age as expected.

  11. Transcriptional profiling reveals progeroid Ercc1-/Δ mice as a model system for glomerular aging

    PubMed Central

    2013-01-01

    Background Aging-related kidney diseases are a major health concern. Currently, models to study renal aging are lacking. Due to a reduced life-span progeroid models hold the promise to facilitate aging studies and allow examination of tissue-specific changes. Defects in genome maintenance in the Ercc1-/Δ progeroid mouse model result in premature aging and typical age-related pathologies. Here, we compared the glomerular transcriptome of young and aged Ercc1-deficient mice to young and aged WT mice in order to establish a novel model for research of aging-related kidney disease. Results In a principal component analysis, age and genotype emerged as first and second principal components. Hierarchical clustering of all 521 genes differentially regulated between young and old WT and young and old Ercc1-/Δ mice showed cluster formation between young WT and Ercc1-/Δ as well as old WT and Ercc1-/Δ samples. An unexpectedly high number of 77 genes were differentially regulated in both WT and Ercc1-/Δ mice (p < 0.0001). GO term enrichment analysis revealed these genes to be involved in immune and inflammatory response, cell death, and chemotaxis. In a network analysis, these genes were part of insulin signaling, chemokine and cytokine signaling and extracellular matrix pathways. Conclusion Beyond insulin signaling, we find chemokine and cytokine signaling as well as modifiers of extracellular matrix composition to be subject to major changes in the aging glomerulus. At the level of the transcriptome, the pattern of gene activities is similar in the progeroid Ercc1-/Δ mouse model constituting a valuable tool for future studies of aging-associated glomerular pathologies. PMID:23947592

  12. 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.

  13. Nonlinear programming models to optimize uneven-aged loblolly pine management

    Treesearch

    Benedict J. Schulte; Joseph. Buongiorno; Kenneth Skog

    1999-01-01

    Nonlinear programming models of uneven-aged loblolly pine (Pinus taeda L.) management were developed to identify sustainable management regimes which optimize: 1) soil expectation value (SEV), 2) tree diversity, or 3) annual sawtimber yields. The models use the equations of SouthPro, a site- and density-dependent, multi-species matrix growth and yield model that...

  14. 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.

  15. 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…

  16. 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…

  17. Lyapunov functions and global stability for SIR and SEIR models with age-dependent susceptibility.

    PubMed

    Melnik, Andrey V; Korobeinikov, Andrei

    2013-04-01

    We consider global asymptotic properties for the SIR and SEIR age structured models for infectious diseases where the susceptibility depends on the age. Using the direct Lyapunov method with Volterra type Lyapunov functions, we establish conditions for the global stability of a unique endemic steady state and the infection-free steady state.

  18. A Diffusion Model Analysis of the Effects of Aging on Recognition Memory

    ERIC Educational Resources Information Center

    Ratcliff, Roger; Thapar, Anjali; McKoon, Gail

    2004-01-01

    The effects of aging on response time were examined in a recognition memory experiment with young, college age subjects and older, 60-75 year old subjects. The older subjects were slower than the young subjects but almost as accurate. Ratcliff's (1978) diffusion model was fit to the data and it provided a good account of response times, their…

  19. 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…

  20. 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…

  1. The Aging and Elderly Population with Mental Retardation: A Model Project in Rural Kentucky.

    ERIC Educational Resources Information Center

    Stone, James A.

    A model to serve rural (Kentucky) mentally retarded adults age 50 and over incorporates generic community resources such as residential, nutritional, medical, recreational, and transportation services with age appropriate activities and programs. The system is intended to provide an alternative to the life-long work setting of the workshop or work…

  2. 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…

  3. Site index model for naturally regenerated even-aged longleaf pine

    Treesearch

    Dwight K. Lauer; John S. Kush

    2013-01-01

    Data from the Regional Longleaf Growth Study (339 permanent sample plots) were used to develop a site index model for naturally regenerated, even-aged longleaf pine (Pinus palustris Mill.). The site index equation was derived using the generalized algebraic difference approach and is base-age invariant. Using height as a measure of site productivity...

  4. Establishment of a model of acetaminophen-induced hepatotoxicity in different weekly-aged ICR mice.

    PubMed

    Taguchi, K; Tokuno, M; Yamasaki, K; Kadowaki, D; Seo, H; Otagiri, M

    2015-10-01

    Acetaminophen (APAP), a widely used analgesic and antipyretic drug, has the potential to cause lethal hepatotoxicity. Mice are widely used for developing murine models of APAP-induced hepatotoxicity, and many researchers have used these models for APAP-related studies including the fields of biology, pharmacology and toxicology. Although drug-induced hepatotoxicity is dependent on a number of factors (species, gender and age), very few studies have investigated the effect of aging on APAP hepatotoxicity. In this study, we evaluated the effect of age on APAP-induced hepatotoxicity in different weekly-aged mice to establish a model of APAP-induced hepatotoxicity that is an accurate reflection of general experimental conditions. Male ICR mice 4, 6, 8, 10 and 12 weeks old were given APAP intraperitoneally, and mortality, hepatic damage and the plasma concentration of APAP metabolites were evaluated. It was found that younger male ICR mice were relatively resistant to hepatotoxicity induced by intraperitoneal APAP administration. In addition, the APAP-glucuronide concentration in plasma remained essentially the same among the differently-aged mice, while APAP-sulfate levels were dramatically decreased in an age-dependent manner. Thus, it is recommended that mice of the same ages be used in studies related to APAP-induced hepatotoxixity. These results provide evidence in support of not only the age-related changes in susceptibility to APAP-derived hepatotoxicity in mice but also in developing mouse models for APAP-related studies.

  5. A Diffusion Model Analysis of the Effects of Aging on Recognition Memory

    ERIC Educational Resources Information Center

    Ratcliff, Roger; Thapar, Anjali; McKoon, Gail

    2004-01-01

    The effects of aging on response time were examined in a recognition memory experiment with young, college age subjects and older, 60-75 year old subjects. The older subjects were slower than the young subjects but almost as accurate. Ratcliff's (1978) diffusion model was fit to the data and it provided a good account of response times, their…

  6. 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…

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. Characterization of plasma thiol redox potential in a common marmoset model of aging.

    PubMed

    Roede, James R; Uppal, Karan; Liang, Yongliang; Promislow, Daniel E L; Wachtman, Lynn M; Jones, Dean P

    2013-01-01

    Due to its short lifespan, ease of use and age-related pathologies that mirror those observed in humans, the common marmoset (Callithrix jacchus) is poised to become a standard nonhuman primate model of aging. Blood and extracellular fluid possess two major thiol-dependent redox nodes involving cysteine (Cys), cystine (CySS), glutathione (GSH) and glutathione disulfide (GSSG). Alteration in these plasma redox nodes significantly affects cellular physiology, and oxidation of the plasma Cys/CySS redox potential (E hCySS) is associated with aging and disease risk in humans. The purpose of this study was to determine age-related changes in plasma redox metabolites and corresponding redox potentials (E h) to further validate the marmoset as a nonhuman primate model of aging. We measured plasma thiol redox states in marmosets and used existing human data with multivariate adaptive regression splines (MARS) to model the relationships between age and redox metabolites. A classification accuracy of 70.2% and an AUC of 0.703 were achieved using the MARS model built from the marmoset redox data to classify the human samples as young or old. These results show that common marmosets provide a useful model for thiol redox biology of aging.

  13. 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.

  14. 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

  15. 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

  16. 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

  17. Drosophila melanogaster as a model system for the evaluation of anti-aging compounds.

    PubMed

    Jafari, Mahtab

    2010-01-01

    Understanding the causes of aging is a complex problem due to the multiple factors that influence aging, which include genetics, environment, metabolism and reproduction, among others. These multiple factors create logistical difficulties in the evaluation of anti-aging agents. There is a need for good model systems to evaluate potential anti-aging compounds. The model systems used should represent the complexities of aging in humans, so that the findings may be extrapolated to human studies, but they should also present an opportunity to minimize the variables so that the experimental results can be accurately interpreted. In addition to positively affecting lifespan, the impact of the compound on the physiologic confounders of aging, including fecundity and the health span--the period of life where an organism is generally healthy and free from serious or chronic illness--of the model organism needs to be evaluated. Fecundity is considered a major confounder of aging in fruit flies. It is well established that female flies that are exposed to toxic substances typically reduce their dietary intake and their reproductive output and display an artifactual lifespan extension. As a result, drugs that achieve longevity benefits by reducing fecundity as a result of diminished food intake are probably not useful candidates for eventual treatment of aging in humans and should be eliminated during the screening process. Drosophila melanogaster provides a suitable model system for the screening of anti-aging compounds as D. melanogaster and humans have many conserved physiological and biological pathways. In this paper, I propose an algorithm to screen anti-aging compounds using Drosophila melanogaster as a model system.

  18. 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

  19. 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

    2015-05-28

    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.

  20. Modeling the multiday evolution and aging of secondary organic aerosol during MILAGRO 2006.

    PubMed

    Dzepina, Katja; Cappa, Christopher D; Volkamer, Rainer M; Madronich, Sasha; Decarlo, Peter F; Zaveri, Rahul A; Jimenez, Jose L

    2011-04-15

    In this study, we apply several recently proposed models to the evolution of secondary organic aerosols (SOA) and organic gases advected from downtown Mexico City at an altitude of ∼3.5 km during three days of aging, in a way that is directly comparable to simulations in regional and global models. We constrain the model with and compare its results to available observations. The model SOA formed from oxidation of volatile organic compounds (V-SOA) when using a non-aging SOA parameterization cannot explain the observed SOA concentrations in aged pollution, despite the increasing importance of the low-NO(x) channel. However, when using an aging SOA parameterization, V-SOA alone is similar to the regional aircraft observations, highlighting the wide diversity in current V-SOA formulations. When the SOA formed from oxidation of semivolatile and intermediate volatility organic vapors (SI-SOA) is computed following Robinson et al. (2007) the model matches the observed SOA mass, but its O/C is ∼2× too low. With the parameterization of Grieshop et al. (2009), the total SOA mass is ∼2× too high, but O/C and volatility are closer to the observations. Heating or dilution cause the evaporation of a substantial fraction of the model SOA; this fraction is reduced by aging although differently for heating vs dilution. Lifting of the airmass to the free-troposphere during dry convection substantially increases SOA by condensation of semivolatile vapors; this effect is reduced by aging.

  1. Characterizing cognitive aging of spatial and contextual memory in animal models

    PubMed Central

    Foster, Thomas C.; DeFazio, R. A.; Bizon, Jennifer L.

    2012-01-01

    Episodic memory, especially memory for contextual or spatial information, is particularly vulnerable to age-related decline in humans and animal models of aging. The continuing improvement of virtual environment technology for testing humans signifies that widely used procedures employed in the animal literature for examining spatial memory could be developed for examining age-related cognitive decline in humans. The current review examines cross species considerations for implementing these tasks and translating findings across different levels of analysis. The specificity of brain systems as well as gaps in linking human and animal laboratory models is discussed. PMID:22988436

  2. 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.

  3. The use of genetically engineered model systems for research on human aging.

    PubMed

    Lepperdinger, Guenter; Berger, Peter; Breitenbach, Michael; Frohlich, Kai-Uwe; Grillari, Johannes; Grubeck-Loebenstein, Beatrix; Madeo, Frank; Minois, Nadege; Zwerschke, Werner; Jansen-Durr, Pidder

    2008-05-01

    A major goal in the field of aging research is to identify molecular mechanisms of aging at the cellular level, which are anticipated to form the basis for the development of age-associated dysfunctions and diseases in human beings. Recent progress in research into model organisms of aging has allowed determining precise molecular mechanisms and genetic determinants of the aging process, which appear to be conserved in evolution and some of which apply to human aging as well. The consortium of the authors focuses on aging mechanisms at the cellular level, and exploits the potential of genetic analyses in lower eukaryotic model organisms for a better understanding of regulatory pathways implicated in aging processes. We have established a new database (GiSAO), which provides a unique resource for the analysis of genome-wide expression patterns as being regulated by senescence, apoptosis and oxidative stress in our model systems. This has led to the identification of candidate genes, which are being tested for their impact on lifespan regulation in yeast, the fruit fly Drosophila melanogaster and the nematode C. elegans.

  4. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. 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.

  6. Toward Reducing Ageism: PEACE (Positive Education about Aging and Contact Experiences) Model.

    PubMed

    Levy, Sheri R

    2016-08-10

    The population of older adults is growing worldwide. Negative ageism (negative attitudes and behavior toward older adults) is a serious international concern that negatively influences not only older adults but also individuals across the age continuum. This article proposes and examines the application of an integrative theoretical model across empirical evidence in the literature on ageism in psychology, medicine, social work, and sociology. The proposed Positive Education about Aging and Contact Experiences (PEACE) model focuses on 2 key contributing factors expected to reduce negative ageism: (a) education about aging including facts on aging along with positive older role models that dispel negative and inaccurate images of older adulthood; and (b) positive contact experiences with older adults that are individualized, provide or promote equal status, are cooperative, involve sharing of personal information, and are sanctioned within the setting. These 2 key contributing factors have the potential to be interconnected and work together to reduce negative stereotypes, aging anxiety, prejudice, and discrimination associated with older adults and aging. This model has implications for policies and programs that can improve the health and well-being of individuals, as well as expand the residential, educational, and career options of individuals across the age continuum.

  7. 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.

  8. 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

  9. Individual-tree diameter growth model for managed, even-aged, upland oak stands

    Treesearch

    Donald E. Hilt

    1983-01-01

    A distance-independent, individual-tree diameter growth model was developed for managed, even-aged, upland oak stands. The 5-year basal-area growth of individual trees is first modeled as a function of dbh squared for given stands. Parameters from these models are then modeled as a function of mean stand diameter, percent stocking of the stand, and site index. A...

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

    PubMed

    Djordjevic, Ivan B

    2015-08-24

    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

  11. Parameterization of European perch Perca fluviatilis length-at-age data using stochastic Gompertz growth models.

    PubMed

    Troynikov, V S; Gorfine, H K; Ložys, L; Pūtys, Z; Jakubavičiūtė, E; Day, R W

    2011-12-01

    Three stochastic versions of the Gompertz growth model were used to parameterize total length (L(T) )-at-age data for perch Perca fluviatilis, an important target species for commercial and recreational fishers and a food species for predatory fishes and aquatic birds. Each model addresses growth heterogeneity by incorporating random parameters from a specific positive distribution: Weibull, gamma or log-normal. The modelling outputs for each version of the model provide L(T) distributions for selected ages and percentiles of L(T) at age for both males and females. The results highlight the importance of using a stochastic approach and the logistic-like growth pattern for analysing growth data for P. fluviatilis in Curonian Lagoon (Lithuania). Outputs from this modelling can be extended to a stochastic analysis of fish cohort dynamics, incorporating all length-based biological relationships, and the selectivity-related interactions between fish cohorts and fishing gear.

  12. 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

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

    PubMed

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

    2015-12-01

    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.

  14. Accelerated failure time models provide a useful statistical framework for aging research.

    PubMed

    Swindell, William R

    2009-03-01

    Survivorship experiments play a central role in aging research and are performed to evaluate whether interventions alter the rate of aging and increase lifespan. The accelerated failure time (AFT) model is seldom used to analyze survivorship data, but offers a potentially useful statistical approach that is based upon the survival curve rather than the hazard function. In this study, AFT models were used to analyze data from 16 survivorship experiments that evaluated the effects of one or more genetic manipulations on mouse lifespan. Most genetic manipulations were found to have a multiplicative effect on survivorship that is independent of age and well-characterized by the AFT model "deceleration factor". AFT model deceleration factors also provided a more intuitive measure of treatment effect than the hazard ratio, and were robust to departures from modeling assumptions. Age-dependent treatment effects, when present, were investigated using quantile regression modeling. These results provide an informative and quantitative summary of survivorship data associated with currently known long-lived mouse models. In addition, from the standpoint of aging research, these statistical approaches have appealing properties and provide valuable tools for the analysis of survivorship data.

  15. 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.

  16. Predicting age-related differences in visual information processing using a two-stage queuing model.

    PubMed

    Ellis, R D; Goldberg, J H; Detweiler, M C

    1996-05-01

    Recent work on age-related differences in some types of visual information processing has qualitatively stated that younger adults are able to develop parallel processing capability, while older adults remain serial processors. A mathematical model based on queuing theory was used to quantitatively predict and parameterize age-related differences in the perceptual encoding and central decision-making aspects of a multiple-frame search task. Statistical results indicated main effects for frame duration, display load, age group, and session of practice. Comparison of the full model and a restricted model indicated an efficient contribution of the encoding speed parameter. The best-fitting parameter set indicated that (1) younger participants processed task information with a two-channel parallel system, while older participants were serial processors; and (2) perceptual encoding had a large impact on age-related differences in task performance. Results are discussed with implications for human factors design principles.

  17. COMPONENT DEGRADATION SUSCEPTIBILITIES AS THE BASES FOR MODELING REACTOR AGING RISK

    SciTech Connect

    Unwin, Stephen D.; Lowry, Peter P.; Toyooka, Michael Y.

    2010-07-18

    The extension of nuclear power plant operating licenses beyond 60 years in the United States will be necessary if we are to meet national energy needs while addressing the issues of carbon and climate. Characterizing the operating risks associated with aging reactors is problematic because the principal tool for risk-informed decision-making, Probabilistic Risk Assessment (PRA), is not ideally-suited to addressing aging systems. The components most likely to drive risk in an aging reactor - the passives - receive limited treatment in PRA, and furthermore, standard PRA methods are based on the assumption of stationary failure rates: a condition unlikely to be met in an aging system. A critical barrier to modeling passives aging on the wide scale required for a PRA is that there is seldom sufficient field data to populate parametric failure models, and nor is there the availability of practical physics models to predict out-year component reliability. The methodology described here circumvents some of these data and modeling needs by using materials degradation metrics, integrated with conventional PRA models, to produce risk importance measures for specific aging mechanisms and component types. We suggest that these measures have multiple applications, from the risk-screening of components to the prioritization of materials research.

  18. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. [Establish Assessment Model of 18 Years of Age in Chinese Han Population by Mandibular Third Molar].

    PubMed

    Fan, Fei; Dai, Xin-hua; Wang, Liang; Li, Yuan; Zhang, Kui; Deng, Zhen-hua

    2016-02-01

    To explore the value of estimating chronologic age based on the grades of mandibular third molar development. To evaluate whether mandibular third molar could be used as an indicator for estimating the age under or over 18 years. The mineralization status of mandibular third molar of 1 845 individuals aged 10 - 30 was graded and marked based on Demirjian's classification of grades reformed by Orhan. Gender difference was examined by t-test. A cubic regression model was established to analyze the correlation between third molar and chronologic age. Each grade of age cumulative distribution diagram and ROC curve was respectively performed to evaluate the relationship between third molar and the age of 18. Using Bayes discriminant analysis, an equation was established for estimating the age of 18. The inner-rater reliability was 0.903. Statistical analysis showed a moderate correlation between age and grade. Significant differences of both genders were found only in grade D and H (P < 0.05). Males at the grades from 1 to D and females at the grades from 1 to C were under 18 years old, and both males and females at grade H were over 18 years old. The area under the ROC curve was 0.797 (P < 0.05). Third molar development shows a high correlation with age, and combined with other indicators, it can be used to estimate the age of 18.

  20. 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

  1. Overexpression of Pa_1_10620 encoding a mitochondrial Podospora anserina protein with homology to superoxide dismutases and ribosomal proteins leads to lifespan extension.

    PubMed

    Grimm, Carolin; Böhl, Lena; Osiewacz, Heinz D

    2015-02-01

    In biological systems, reactive oxygen species (ROS) represent 'double edged swords': as signaling molecules they are essential for proper development, as reactive agents they cause molecular damage and adverse effects like degeneration and aging. A well-coordinated control of ROS is therefore of key importance. Superoxide dismutases (SODs) are enzymes active in the detoxification of superoxide. The number of isoforms of these proteins varies among species. Here we report the characterization of the putative protein encoded by Pa_1_10620 that has been previously annotated to code for a mitochondrial ribosomal protein but shares also sequence domains with SODs. We report that the gene is transcribed in P. anserina cultures of all ages and that the encoded protein localizes to mitochondria. In strains overexpressing Pa_1_10620 in a genetic background in which PaSod3, the mitochondrial MnSOD of P. anserina, is deleted, no SOD activity could be identified in isolated mitochondria. However, overexpression of the gene leads to lifespan extension suggesting a pro-survival function of the protein in P. anserina.

  2. A survival model for individual shortleaf pine trees in even-aged natural stands

    Treesearch

    Thomas B. Lynch; Michael M. Huebschmann; Paul A. Murphy

    2000-01-01

    A model was developed that predicts the probability of survival for individual shortleaf pine (Pinus echinata Mill.) trees growing in even-aged natural stands. Data for model development were obtained from the first two measurements of permanently established plots located in naturally occurring shortleaf pine forests on the Ouachita and...

  3. A survival model for individual shortleaf pine trees in even-aged natural stands

    Treesearch

    Thomas B. Lynch; Michael M. Huebschmann; Paul A. Murphy

    2000-01-01

    A model was developed that predicts the probability of survival for individual shortleaf pine (Pinus echinata Mill.) trees growing in even-aged natural stands. Data for model development were obtained from the first two measurements of permanently established plots located in naturally occurring shortleaf pine forests on the Ouachita and Ozark...

  4. A Survival Model for Shortleaf Pine Tress Growing in Uneven-Aged Stands

    Treesearch

    Thomas B. Lynch; Lawrence R. Gering; Michael M. Huebschmann; Paul A. Murphy

    1999-01-01

    A survival model for shortleaf pine (Pinus echinata Mill.) trees growing in uneven-aged stands was developed using data from permanently established plots maintained by an industrial forestry company in western Arkansas. Parameters were fitted to a logistic regression model with a Bernoulli dependent variable in which "0" represented...

  5. Growth model for uneven-aged loblolly pine stands : simulations and management implications

    Treesearch

    C.-R. Lin; J. Buongiorno; Jeffrey P. Prestemon; K. E. Skog

    1998-01-01

    A density-dependent matrix growth model of uneven-aged loblolly pine stands was developed with data from 991 permanent plots in the southern United States. The model predicts the number of pine, soft hardwood, and hard hardwood trees in 13 diameter classes, based on equations for ingrowth, upgrowth, and mortality. Projections of 6 to 10 years agreed with the growth...

  6. 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 ...

  7. Nonlinear Programming Models to Optimize Uneven-Aged Shortleaf Pine Management

    Treesearch

    Benedict J. Schulte; Joseph Buongiorno

    2002-01-01

    Nonlinear programming models of uneven-aged shortleaf pine (Pinus echinata Mill.) management were developed to identify sustainable management regimes that optimize soil expectation value (SEV) or annual sawtimber yields. The models recognize three species groups (shortleaf pine and other softwoods, soft hardwoods and hard hardwoods) and 13 2-inch...

  8. 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 ...

  9. Sensitivity Analysis of Hierarchical Models for the Ages of Galactic Halo White Dwarfs

    NASA Astrophysics Data System (ADS)

    Si, S.; van Dyk, D. A.; von Hippel, T.

    2017-03-01

    The ages of white dwarfs are of great importance in stellar evolution. Si et al. developed a novel approach to increase the precision of such estimates by combining multiple white dwarfs in a Bayesian hierarchical model. In this paper, we further investigate the robustness of the Bayesian hierarchical model by performing a simulation study.

  10. Aging Influence on Gray Matter Structural Associations within the Default Mode Network Utilizing Bayesian Network Modeling.

    PubMed

    Wang, Yan; Chen, Kewei; Zhang, Jiacai; Yao, Li; Li, Ke; Jin, Zhen; Ye, Qing; Guo, Xiaojuan

    2014-01-01

    Recent neuroimaging studies have revealed normal aging-related alterations in functional and structural brain networks such as the default mode network (DMN). However, less is understood about specific brain structural dependencies or interactions between brain regions within the DMN in the normal aging process. In this study, using Bayesian network (BN) modeling, we analyzed gray matter volume data from 109 young and 82 old subjects to characterize the influence of aging on associations between core brain regions within the DMN. Furthermore, we investigated the discriminability of the aging-associated BN models for the young and old groups. Compared to their young counterparts, the old subjects showed significant reductions in connections from right inferior temporal cortex (ITC) to medial prefrontal cortex (mPFC), right hippocampus (HP) to right ITC, and mPFC to posterior cingulate cortex and increases in connections from left HP to mPFC and right inferior parietal cortex to right ITC. Moreover, the classification results showed that the aging-related BN models could predict group membership with 88.48% accuracy, 88.07% sensitivity, and 89.02% specificity. Our findings suggest that structural associations within the DMN may be affected by normal aging and provide crucial information about aging effects on brain structural networks.

  11. The Werner syndrome. A model for the study of human aging.

    PubMed

    Nehlin, J O; Skovgaard, G L; Bohr, V A

    2000-06-01

    Human aging is a complex process that leads to the gradual deterioration of body functions with time. Various models to approach the study of aging have been launched over the years such as the genetic analysis of life span in the yeast S. cerevisiae, the worm C. elegans, the fruitfly, and mouse, among others. In human models, there have been extensive efforts using replicative senescence, the study of centenerians, comparisons of young versus old at the organismal, cellular, and molecular levels, and the study of premature aging syndromes to understand the mechanisms leading to aging. One good model for studying human aging is a rare autosomal recessive disorder known as the Werner syndrome (WS), which is characterized by accelerated aging in vivo and in vitro. A genetic defect implicated in WS was mapped to the WRN locus. Mutations in this gene are believed to be associated, early in adulthood, with clinical symptoms normally found in old individuals. WRN functions as a DNA helicase, and recent evidence, summarized in this review, suggests specific biochemical roles for this multifaceted protein. The interaction of WRN protein with RPA (replication protein A) and p53 will undoubtedly direct efforts to further dissect the genetic pathway(s) in which WRN protein functions in DNA metabolism and will help to unravel its contribution to the human aging process.

  12. Age-related structural changes in upper extremity muscle tissue in a nonhuman primate model.

    PubMed

    Santago, Anthony C; Plate, Johannes F; Shively, Carol A; Register, Thomas C; Smith, Thomas L; Saul, Katherine R

    2015-10-01

    Longitudinal studies of upper extremity aging in humans include logistical concerns that animal models can overcome. The vervet is a promising species with which to study aging-related processes. However, age-related changes in upper extremity muscle structure have not been quantified in this species. This study measured age-related changes to muscle structure, examined relationships between muscle structure and measures of physical performance, and evaluated the presence of rotator cuff tears. Muscle structure (volume, optimal fiber length, and physiologic cross-sectional area (PCSA)) of 10 upper extremity muscles was quantified from the right upper limb of 5 middle-aged and 6 older adult female vervets. Total measured PCSA was smaller (P = .001) in the older adult vervets than in the middle-aged vervets. Muscle volume reduction predominate the age-related reductions in PCSA. Total measured PCSA was not correlated to any measures of physical performance. No rotator cuff tears were observed. Supraspinatus volume was relatively larger and deltoid volume relatively smaller in the vervet compared with a human. The vervet is an appropriate translational model for age-related upper extremity muscle volume loss. Functional measures were not correlated to PCSA, suggesting the vervets may have enough strength for normal function despite loss of muscle tissue. Reduced relative demand on the supraspinatus may be responsible for the lack of naturally occurring rotator cuff tears. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  13. 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.

  14. 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

  15. A mouse model of accelerated liver aging due to a defect in DNA repair

    PubMed Central

    Gregg, Siobhán Q.; Gutiérrez, Verónica; Robinson, Andria Rasile; Woodell, Tyler; Nakao, Atsunori; Ross, Mark A.; Michalopoulos, George K.; Rigatti, Lora; Rothermel, Carrie E.; Kamileri, Irene; Garinis, George; Stolz, Donna Beer; Niedernhofer, Laura J.

    2011-01-01

    The liver changes with age leading to an impaired ability to respond to hepatic insults and increased incidence of liver disease in the elderly. Therefore, there is critical need for rapid model systems to study aging-related liver changes. One potential opportunity is murine models of human progerias, or diseases of accelerated aging. Ercc1−/Δ mice model a rare human progeroid syndrome caused by inherited defects in DNA repair. To determine if hepatic changes that occur with normal aging occur prematurely in Ercc1−/Δ mice, we systematically compared liver from 5 month-old, progeroid Ercc1−/Δ mice to old (24–36 month) wild-type (WT) mice. Both displayed areas of necrosis, foci of hepatocellular degeneration and acute inflammation. Loss of hepatic architecture, fibrosis, steatosis, pseudocapillarization, and anisokaryosis were more dramatic in Ercc1−/Δ mice than in old WT mice. Liver enzymes were significantly elevated in serum of Ercc1−/Δ mice and old WT mice, while albumin was reduced, demonstrating liver damage and dysfunction. The regenerative capacity of Ercc1−/Δ liver following partial hepatectomy was significantly reduced. There was evidence of increased oxidative damage in Ercc1−/Δ and old WT liver, including lipofuscin, lipid hydroperoxides and acrolein as well as increased hepatocellular senescence. There was a highly significant correlation in genome-wide transcriptional changes between old WT and 16 but not 5 week-old Ercc1−/Δ mice emphasizing that the Ercc1−/Δ mice acquire an aging profile in early adulthood. Conclusion There are strong functional, regulatory and histopathological parallels between accelerated aging driven by a DNA repair defect and normal aging. This supports a role for DNA damage in driving aging and validates a murine model for rapidly testing hypotheses about causes and treatment for aging-related hepatic changes. PMID:21953681

  16. How aging and bilingualism influence language processing: theoretical and neural models

    PubMed Central

    Rossi, Eleonora; Diaz, Michele T.

    2016-01-01

    Healthy non-pathological aging is characterized by cognitive and neural decline, and although language is one of the more stable areas of cognition, older adults often show deficits in language production, showing word finding failures, increased slips of the tongue, and increased pauses in speech. Overall, research on language comprehension in older healthy adults show that it is more preserved than language production. Bilingualism has been shown to confer a great deal of neuroplasticity across the life span, including a number of cognitive benefits especially in executive functions such as cognitive control. Many models of bilingual language processing have been proposed to explain bilingual language processing. However, the question remains open of how such models might be modulated by age-related changes in language. Here, we discuss how current models of language processing in non-pathological aging, and models of bilingual language processing can be integrated to provide new research directions. PMID:28919933

  17. A structural equation model of environmental correlates of adolescent obesity for age and gender groups.

    PubMed

    Nesbit, K C; Kolobe, T H; Sisson, S B; Ghement, I R

    2015-08-01

    The relationships between environmental correlates of adolescent obesity are complex and not yet well defined by current research, especially when considering age and gender. The purpose of this study was to test a model of proximal (home) and distal (neighbourhood) environmental correlates of obesity for adolescent age and gender groups. This was a descriptive, cross-sectional study, using the 2007 National Survey of Children's Health of 39 542 children ages 11-17 years. The model fit the data well for early adolescents (ages 11-14 years) (root mean square standard error of approximation [RMSEA] 0.040, 90% confidence interval [CI]: 0.039-0.041; comparative fit index [CFI] 0.947; Tucker-Lewis index [TLI] 0.929) and middle adolescents (ages 15-17 years) (RMSEA 0.037, 90% CI: 0.036-0.038; CFI 0.052; TLI 0.937). The model also fit the data well for boy adolescents (RMSEA 0.038, 90% CI: 0.037-0.039; CFI 0.951; TLI 0.935) and girl adolescents (RMSEA 0.038, 90% CI: 0.037-0.040; CFI 0.949; TLI 0.932). All models provide loadings of the environmental correlates of adolescent obesity for specific age and gender groups that can be used for early identification of risks and targeted interventions. © 2014 World Obesity.

  18. 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

  19. 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

  20. Mechanism of Origin of Conduction Disturbances in Aging Human Atrial Bundles: Experimental and Model Study

    PubMed Central

    Spach, Madison S.; Heidlage, J. Francis; Dolber, Paul C.; Barr, Roger C.

    2007-01-01

    BACKGROUND Aging is associated with a significant increase in atrial tachyarrhythmias, especially atrial fibrillation. A macroscopic repolarization gradient created artificially by a stimulus at one site prior to a premature stimulus from a second site is widely considered to be part of the experimental protocol necessary for the initiation of such arrhythmias in the laboratory. How such gradients occur naturally in aging atrial tissue has remained unknown. OBJECTIVE This study was to determine if the pattern of cellular connectivity in aging human atrial bundles produces a mechanism for variable early premature responses. METHODS Extracellular and intracellular potentials were recorded following control and premature stimuli at a single site in aging human atrial bundles. We also measured cellular geometry, the distribution of connexins, and the distribution of collagenous septa. A model of the atrial bundles was constructed based on the morphological results. Action potential propagation and the sodium current were analyzed following premature stimuli in the model. RESULTS Similar extracellular potential waveform responses occurred following early premature stimuli in the aging bundles and in the model. Variable premature conduction patterns were accounted for by the single model of aging atrial structure. A major feature of the model results was that the conduction events and the magnitude of the sodium current at multiple sites were very sensitive to small changes in the location and the timing of premature stimuli. CONCLUSION In aging human atrial bundles stimulated from only a single site, premature stimuli induce variable arrhythmogenic conduction responses. The generation of these responses is greatly enhanced by remodeling of cellular connectivity during aging. The results provide insight into sodium current-structural interactions as a general mechanism of arrhythmogenic atrial responses to premature stimuli. PMID:17275753

  1. 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

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

    PubMed

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

    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 micromol/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.

  3. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Age structure and capital dilution effects in neo-classical growth models.

    PubMed

    Blanchet, D

    1988-01-01

    Economists often over estimate capital dilution effects when applying neoclassical growth models which use age structured population and depreciation of capital stock. This occurs because capital stock is improperly characterized. A standard model which assumes a constant depreciation of capital intimates that a population growth rate equal to a negative constant savings ratio is preferable to any higher growth rate. Growth rates which are lower than a negative constant savings ratio suggest an ever growing capital/labor ratio and an ever growing standard of living, even if people do not save. This is suggested because the natural reduction of the capital stock through depreciation is slower than the population decrease which is simply unrealistic. This model overlooks the fact that low or negative growth rates result in an ageing of the capital stock, and this ageing subsequently results in an increase of the overall rate of capital depreciation. In that overly simplistic model, depreciation was assumed independent of the age of the captial stock. Incorporating depreciation as a variable into a model allows a more symmetric treatment of capital. Using models with heterogenous capital, this article explores what occurs when more than 1 kind of capital good is involved in production and when these various captial goods have different lengths of life. Applying economic models, it also examines what occurs when the length of life of capital may vary. These variations correct the negative impact that population growth can have on per capital production and consumption.

  5. Sympathetic modulation of sensory nerve activity with age: human and rodent skin models.

    PubMed

    Khalil, Z; LeVasseur, S; Merhi, M; Helme, R D

    1997-11-01

    1. Sensory nerves serve an afferent role and mediate neurogenic components of inflammation and tissue repair via an axon reflex release of sensory peptides at sites of injury. Dysfunction of these nerves with age could contribute to delayed tissue healing. 2. Complementary animal and human skin models were used in the present studies to investigate changes in the modulation of sensory nerve function by sympathetic efferents during ageing. Laser Doppler flowmetry was used to monitor neurogenic skin vascular responses. 3. The animal model used skin of the hind footpad of anaesthetized rats combined with electrical stimulation of the sciatic nerve, while the human model comprised capsaicin electrophoresis to the volar surface of the forearm. Sympathetic modulation was effected by systemic phentolamine pretreatment in animals and local application in the human model. 4. The results obtained from the human model confirmed the reported decline in sensory nerve function and showed no change in sympathetic modulation with age. The results from the animal model confirm and expand results obtained from the human model. 5. The use of low (5 Hz) and high (15 Hz) frequency electrical stimulation (20 V, 2 ms for 1 min) revealed a preferential response of aged sensory nerves to low-frequency electrical stimulation parameters with differential sympathetic modulation that is dependent on the frequency of stimulation.

  6. Normal and diseased personal eye modeling using age-appropriate lens parameters

    PubMed Central

    Chen, Ying-Ling; Shi, L.; Lewis, J. W. L.; Wang, M.

    2012-01-01

    Personalized eye modeling of normal and diseased eye conditions is attractive due to the recent availability of detailed ocular measurements in clinic environments and the promise of its medical and industrial applications. In the customized modeling, the optical properties of the crystalline lens including the gradient refractive index, the lens bio-geometry and orientation are typically assigned with average lens parameters from literature since typically they are not clinically available. Although, through the optical optimization by assigning lens parameters as variables, the clinical measured wavefront aberration can be achieved, the optimized lens biometry and orientation often end up at edges of the statistical distribution. Without an effective validation of these models today, the fidelity of the final lens (and therefore the model) remains questionable. To develop a more reliable customized model without detailed lens information, we incorporate age-appropriate lens parameters as the initial condition of optical optimization. A biconic lens optimization was first performed to provide a correct lens profile for accurate lower order aberration and then followed by the wavefront optimization. Clinical subjects were selected from all ages with both normal and diseased corneal and refractive conditions. 19 ammetropic eyes ( + 4D to −11D), and 16 keratoconus eyes (mild to moderate with cylinder 0.25 to 6D) were modeled. Age- and gender-corrected refractive index was evaluated. Final models attained the lens shapes comparable to the statistical distribution in their age. PMID:22714237

  7. Damage Mechanisms of Filled Siloxanes for Predictive Multiscale Modeling of Aging Behavior

    SciTech Connect

    Balazs, B; Maxwell, R; de Teresa, S; Dinh, L; Gee, R

    2002-04-02

    Predictions of component performance versus lifetime are often risky for complex materials in which there may be many underlying aging or degradation mechanisms. In order to develop more accurate predictive models for silica-filled siloxane components, we are studying damage mechanisms over a broad range of size domains, linked together through several modeling efforts. Atomistic and molecular dynamic modeling has elucidated the chemistry of the silica filler to polymer interaction, as this interaction plays a key role in this material's aging behavior. This modeling work has been supported by experimental data on the removal of water from the silica surface, the effect of the surrounding polymer on this desiccation, and on the subsequent change in the mechanical properties of the system. Solid State NMR efforts have characterized the evolution of the polymer and filler dynamics as the material is damaged through irradiation or desiccation. These damage signatures have been confirmed by direct measurements of changes in polymer crosslink density and filler interaction as measured by solvent swelling, and by mechanical property tests. Data from the changes at these molecular levels are simultaneously feeding the development of age-aware constitutive models for polymer behavior. In addition, the microstructure of the foam, including under load, has been determined by Computed Tomography, and this data is being introduced into Finite Element Analysis codes to allow component level models. All of these techniques are directed towards the incorporation of molecular and microstructural aging signatures into predictive models for overall component performance.

  8. The quadratic hazard model for analyzing longitudinal data on aging, health, and the life span.

    PubMed

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

    2012-06-01

    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.

  9. Spectral ageing in the era of big data: integrated versus resolved models

    NASA Astrophysics Data System (ADS)

    Harwood, Jeremy J.

    2017-04-01

    Continuous injection models of spectral ageing have long been used to determine the age of radio galaxies from their integrated spectrum; however, many questions about their reliability remain unanswered. With various large area surveys imminent (e.g. LOw Frequency ARray, MeerKAT, Murchison Widefield Array) and planning for the next generation of radio interferometers are well underway (e.g. next generation VLA, Square Kilometre Array), investigations of radio galaxy physics are set to shift away from studies of individual sources to the population as a whole. Determining if and how integrated models of spectral ageing can be applied in the era of big data is therefore crucial. In this paper, I compare classical integrated models of spectral ageing to recent well-resolved studies that use modern analysis techniques on small spatial scales to determine their robustness and validity as a source selection method. I find that integrated models are unable to recover key parameters and, even when known a priori, provide a poor, frequency-dependent description of a source's spectrum. I show a disparity of up to a factor of 6 in age between the integrated and resolved methods but suggest, even with these inconsistencies, such models still provide a potential method of candidate selection in the search for remnant radio galaxies and in providing a cleaner selection of high redshift radio galaxies in z - α selected samples.

  10. Evaluating Health Span in Preclinical Models of Aging and Disease: Guidelines, Challenges, and Opportunities for Geroscience

    PubMed Central

    Huffman, Derek M.; Justice, Jamie N.; Stout, Michael B.; Kirkland, James L.; Barzilai, Nir

    2016-01-01

    Life extension is no longer considered sufficient evidence of delayed aging in research animals. It must also be demonstrated that a broad swathe of health indicators have been extended. During a retreat of the Geroscience Network, a consortium of basic and clinical aging researchers, potential measures of mouse health were considered for their potential as easily standardized, highly informative metrics. Major health domains considered were neuromuscular, cognitive, cardiovascular, metabolic, and inflammatory functions as well as body composition and energetics and a multitude of assays interrogating these domains. A particularly sensitive metric of health is the ability to respond to, and recover, from stress. Therefore, the Network also considered stresses of human relevance that could be implemented in mouse models to assess frailty and resilience. Mouse models already exist for responses to forced immobility, cancer chemotherapy, infectious diseases, dietary challenges, and surgical stress, and it was felt that these could be employed to determine whether putative senescence-retarding interventions increased and extended organismal robustness. The Network discussed challenges in modeling age-related human chronic diseases and concluded that more attention needs to be paid to developing disease models with later age of onset, models of co- and multimorbidity, diversifying the strains and sexes commonly used in aging research, and considering additional species. PMID:27535967

  11. The quadratic hazard model for analyzing longitudinal data on aging, health, and the life span

    NASA Astrophysics Data System (ADS)

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

    2012-06-01

    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.

  12. Groundwater ages in an alluvial aquifer: Confronting lumped parameter models (3H, CFCs and SF6) and numerical transport modeling.

    NASA Astrophysics Data System (ADS)

    Mouloudi, R.; Gourcy, L.; Kloppmann, W.; Violette, S.

    2012-04-01

    Groundwater age dating using tritium and dissolved gases was undertaken in an alluvial aquifer to determine groundwater transit time and flow rate as key parameters for assessing diffuse nitrate pollution.The studied site of about 260 km2 is crossed by the Ain River and bordered by the Rhône River which is the natural drain for the aquifer. It is mainly recharged by precipitation but also receives water from the Dombes plain (NW and W), intensively cultivated, and from the Bugey and Jura karstic mountains (NE and E part). In this study, we investigated the relevance of the gas-tracers CFCs and SF6 as age dating tools in alluvial shallow aquifers. The exponential model was chosen to conceptualize the alluvial aquifer recharge, 3H also used. Age-dating gave a mean recharge date of 5 to 18 years. CFCs, SF6 and 3H age estimation was confronted with the results of 2D transport modelling. Lumped parameter models were used to estimate the distribution of CFC and SF6 ages. Groundwater age is a measurable quantity, provided many assumptions. One of the underlying questions is the physical meaning of "ages" obtained by the lumped parameter models. Indeed, knowledge of an apparent age does not necessarily imply knowledge of the groundwater residence time. An independent approach of groundwater age determination is based on solving the solute transport problem. Few studies seek to compare the hydrodynamic and tracers approaches. This comparison aims to increase our hydrogeological understanding of the Ain alluvial plain and to better define " groundwater age" and its meanings. The hydrodynamic modelling was performed using MARTHE code (Thiéry, 2004). It was calibrated over a period of 8 years at a 10 days' time step. Results of the transitory regime calibration are satisfactory and allowed the use of this model for solute transport of 3H, CFCs and SF6. Different approaches are possible for the comparison of tracer and hydrodynamic models. The first is to reproduce the tracer

  13. Fission yeast and other yeasts as emergent models to unravel cellular aging in eukaryotes.

    PubMed

    Roux, Antoine E; Chartrand, Pascal; Ferbeyre, Gerardo; Rokeach, Luis A

    2010-01-01

    In the past years, simple organisms such as yeasts and worms have contributed a great deal to aging research. Studies pioneered in Saccharomyces cerevisiae were useful to elucidate a significant number of molecular mechanisms underlying cellular aging and to discover novel longevity genes. Importantly, these genes proved many times to be conserved in multicellular eukaryotes. Consequently, such discovery approaches are being extended to other yeast models, such as Schizosaccharomyces pombe, Candida albicans, Kluyveromyces lactis, and Cryptococcus neoformans. In fission yeast, researchers have found links between asymmetrical cell division and nutrient signaling pathways with aging. In this review, we discuss the state of knowledge on the mechanisms controlling both replicative and chronological aging in S pombe and the other emergent yeast models.

  14. 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.

  15. Age-related Dysregulation of Inflammation and Innate Immunity: Lessons Learned from Rodent Models

    PubMed Central

    Brubaker, Aleah L.; Palmer, Jessica L.; Kovacs, Elizabeth J.

    2011-01-01

    In the elderly patient population, it has become increasingly evident that immune dysregulation is a contributing factor to age-related pathologies and their associated morbidity and mortality. In particular, elderly subjects are plagued by poor responses to infectious challenge and immunization and are at heightened risk for the development of autoimmune, neuroinflammatory and tumor-associated pathologies. Rodent models of aging and age-related disorders have been utilized to better describe how innate immune cell dysfunction contributes to these clinical scenarios. As the elderly population continues to increase in size, use of these aging rodent models to study immune dysregulation may translate into increased healthy living years for these individuals. PMID:22396887

  16. 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.

  17. 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.

  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. Developmental trajectories of verbal and visuospatial abilities in healthy older adults: comparison of the hemisphere asymmetry reduction in older adults model and the right hemi-ageing model.

    PubMed

    Hatta, Takeshi; Iwahara, Akihiko; Hatta, Taketoshi; Ito, Emi; Hatta, Junko; Hotta, Chie; Nagahara, Naoko; Fujiwara, Kazumi; Hamajima, Nobuyuki

    2015-01-01

    Two models of cognitive ageing, the hemisphere asymmetry reduction in older adults (HAROLD) model and the right hemi-ageing model, were compared based upon the verbal memory and visuospatial task performance of 338 elderly participants. Comparison of the developmental trajectories for four age groups (50s, 60s, 70s and 80s) supported the HAROLD model, but not the right hemi-ageing model. Performance differences between the verbal memory and visuospatial tasks in the earlier age groups decreased in the later age groups. There was a sex difference in the cognitive-decline trajectories for verbal and visuospatial task performance after the 50s.

  20. Aging-like skin changes in metabolic syndrome model mice are mediated by mineralocorticoid receptor signaling.

    PubMed

    Nagase, Takashi; Akase, Tomoko; Sanada, Hiromi; Minematsu, Takeo; Ibuki, Ai; Huang, Lijuan; Asada, Mayumi; Yoshimura, Kotaro; Nagase, Miki; Shimada, Tsutomu; Aburada, Masaki; Nakagami, Gojiro; Sugama, Junko

    2013-02-01

    Aging is accelerated, at least in part, by pathological condition such as metabolic syndrome (MetS), and various molecular pathways such as oxidative stress are common mediators of aging and MetS. We previously developed the aging-like skin model by single ultraviolet (UV) irradiation on the MetS model mice. Recent studies revealed that mineralocorticoid receptor (MR) signaling plays a pivotal role for various tissue inflammation and damages in MetS. Although previous studies reported that MR is expressed in the skin and that overexpression of MR in the skin resulted in the skin atrophy, the physiological or pathological functions of MR in the skin are not fully elucidated. Here, we show the involvement of MR signaling in the aging-like skin changes in our own model. Elevations of oxidative stress and inflammation markers were observed in the MetS mice, and the UV-evoked aging-like skin damages were attenuated by topical antioxidant. MR expression was higher in the MetS mouse skin, and notably, expression of its effecter gene Sgk1 was significantly upregulated in the aging-like skin in the UV-irradiated MetS mice. Furthermore, topical application of MR antagonist spironolactone suppressed Sgk1 expression, oxidative stress, inflammation, and the aging-like changes in the skin. The 2-week UV onto the non-MetS mice, the more usual photoaging model, resulted in the skin damages mostly equivalent to the MetS mice with single UV, but they were not associated with upregulation of MR signaling. Our studies suggested an unexpected role of MR signaling in the skin aging in MetS status.

  1. The effect of aging on posterior intertransverse lumbar fusion: a New Zealand white rabbit model.

    PubMed

    Daubs, Michael D; Tyser, Andy; Lawrence, Brandon D; Sinclair, Sarina K; Patel, Alpesh A; Adams, Jacob; Brodke, Darrel S

    2015-03-01

    In vivo assessment of lumbar spinal fusion between a younger and older cohort of New Zealand white rabbits. Directly compare fusion within young and aged New Zealand white rabbits to establish an aged spinal fusion model translational research. Prior studies have utilized skeletally mature young rabbits (6-12 mo old) that may not be appropriate as an analog for studying the aging human spine. Ten aged (>36 mo old) and 10 young (12 mo old) New Zealand white rabbits underwent a single-level, bilateral, L5-6 posterolateral intertransverse fusion using autogenous iliac crest bone graft. The animals were killed at 6 weeks postoperatively, and the specimens were then evaluated with quantitative microcomputerized tomography and manual palpation by 6 orthopedic surgeons. The fusions were graded as either fused or not fused by each examiner. The spines were then embedded in poly(methyl methacrylate) and cut into 2-mm-thick sections for histologic analysis. A higher percentage of young rabbits were determined to be successfully fused through manual palpation testing compared with the aged rabbits. Micro-computed tomography (CT) analysis revealed a significantly greater fusion mass volume in the younger rabbits than in the older cohort. In addition, the fusion density of the younger rabbits was found to be significantly lower than that of the older rabbits when normalized to the bone density in the nonfused portion of the spine. Histologic analysis showed that the quality of the bone within the fusion mass was consistent between the young and old rabbits. A greater number of young animals had bilateral continuous bone graft compared with the aged animals. The aged (>36 mo) New Zealand white rabbit model appears to be a valid model to evaluate the effect of aging on lumbar fusion and has the potential to more accurately model conditions that are present in the older human spine.

  2. Effect of aging and damage on the brain modelled by a phase transition

    NASA Astrophysics Data System (ADS)

    Miyazima, Sasuke; Sakakibara, Mitsuharu

    1992-03-01

    Aging and the effects of damage on the brain are considered on the basis of the Hopfield model. As the damage to the brain or the debility of neurons is increased by aging, a sudden change similar to critical phenomena is observed in the ability to retrieve information or in recognition. This type of critical behavior is very similar to the percolation phenomenon in physics. Furthermore the relearning effect, which corresponds to so-called rehabilitation, is discussed.

  3. 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.

  4. A whole-body mathematical model of cholesterol metabolism and its age-associated dysregulation

    PubMed Central

    2012-01-01

    Background Global demographic changes have stimulated marked interest in the process of aging. There has been, and will continue to be, an unrelenting rise in the number of the oldest old ( >85 years of age). Together with an ageing population there comes an increase in the prevalence of age related disease. Of the diseases of ageing, cardiovascular disease (CVD) has by far the highest prevalence. It is regarded that a finely tuned lipid profile may help to prevent CVD as there is a long established relationship between alterations to lipid metabolism and CVD risk. In fact elevated plasma cholesterol, particularly Low Density Lipoprotein Cholesterol (LDL-C) has consistently stood out as a risk factor for having a cardiovascular event. Moreover it is widely acknowledged that LDL-C may rise with age in both sexes in a wide variety of groups. The aim of this work was to use a whole-body mathematical model to investigate why LDL-C rises with age, and to test the hypothesis that mechanistic changes to cholesterol absorption and LDL-C removal from the plasma are responsible for the rise. The whole-body mechanistic nature of the model differs from previous models of cholesterol metabolism which have either focused on intracellular cholesterol homeostasis or have concentrated on an isolated area of lipoprotein dynamics. The model integrates both current and previously published data relating to molecular biology, physiology, ageing and nutrition in an integrated fashion. Results The model was used to test the hypothesis that alterations to the rate of cholesterol absorption and changes to the rate of removal of LDL-C from the plasma are integral to understanding why LDL-C rises with age. The model demonstrates that increasing the rate of intestinal cholesterol absorption from 50% to 80% by age 65 years can result in an increase of LDL-C by as much as 34 mg/dL in a hypothetical male subject. The model also shows that decreasing the rate of hepatic clearance of LDL

  5. Oxidative damage and cellular defense mechanisms in sea urchin models of aging.

    PubMed

    Du, Colin; Anderson, Arielle; Lortie, Mae; Parsons, Rachel; Bodnar, Andrea

    2013-10-01

    The free radical, or oxidative stress, theory of aging proposes that the accumulation of oxidative cellular damage is a major contributor to the aging process and a key determinant of species longevity. This study investigates the oxidative stress theory in a novel model for aging research, the sea urchin. Sea urchins present a unique model for the study of aging because of the existence of species with tremendously different natural life spans, including some species with extraordinary longevity and negligible senescence. Cellular oxidative damage, antioxidant capacity, and proteasome enzyme activities were measured in the tissues of three sea urchin species: short-lived Lytechinus variegatus, long-lived Strongylocentrotus franciscanus, and Strongylocentrotus purpuratus, which has an intermediate life span. Levels of protein carbonyls and 4-hydroxynonenal measured in tissues (muscle, nerve, esophagus, gonad, coelomocytes, ampullae) and 8-hydroxy-2'-deoxyguanosine measured in cell-free coelomic fluid showed no general increase with age. The fluorescent age pigment lipofuscin, measured in muscle, nerve, and esophagus, increased with age; however, it appeared to be predominantly extracellular. Antioxidant mechanisms (total antioxidant capacity, superoxide dismutase) and proteasome enzyme activities were maintained with age. In some instances, levels of oxidative damage were lower and antioxidant activity higher in cells or tissues of the long-lived species compared to the short-lived species; however, further studies are required to determine the relationship between oxidative damage and longevity in these animals. Consistent with the predictions of the oxidative stress theory of aging, the results suggest that negligible senescence is accompanied by a lack of accumulation of cellular oxidative damage with age, and maintenance of antioxidant capacity and proteasome enzyme activities may be important mechanisms to mitigate damage.

  6. Oxidative Damage and Cellular Defense Mechanisms in Sea Urchin Models of Aging

    PubMed Central

    Du, Colin; Anderson, Arielle; Lortie, Mae; Parsons, Rachel; Bodnar, Andrea

    2013-01-01

    The free radical or oxidative stress theory of aging proposes that the accumulation of oxidative cellular damage is a major contributor to the aging process and a key determinant of species longevity. This study investigates the oxidative stress theory in a novel model for aging research, the sea urchin. Sea urchins present a unique model for the study of aging due to the existence of species with tremendously different natural life spans including some species with extraordinary longevity and negligible senescence. Cellular oxidative damage, antioxidant capacity and proteasome enzyme activities were measured in the tissues of three sea urchin species: short-lived Lytechinus variegatus, long-lived Strongylocentrotus franciscanus and Strongylocentrotus purpuratus which has an intermediate lifespan. Levels of protein carbonyls and 4-hydroxynonenal (HNE) measured in tissues (muscle, nerve, esophagus, gonad, coelomocytes, ampullae) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) measured in cell-free coelomic fluid showed no general increase with age. The fluorescent age-pigment lipofuscin measured in muscle, nerve and esophagus, increased with age however it appeared to be predominantly extracellular. Antioxidant mechanisms (total antioxidant capacity, superoxide dismutase) and proteasome enzyme activities were maintained with age. In some instances, levels of oxidative damage were lower and antioxidant activity higher in cells or tissues of the long-lived species compared to the short-lived species, however further studies are required to determine the relationship between oxidative damage and longevity in these animals. Consistent with the predictions of the oxidative stress theory of aging, the results suggest that negligible senescence is accompanied by a lack of accumulation of cellular oxidative damage with age and maintenance of antioxidant capacity and proteasome enzyme activities may be important mechanisms to mitigate damage. PMID:23707327

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

    PubMed

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

    2016-01-01

    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. 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). 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% among males ages 10-29, and 55% among males ages 30-34.

  8. Senescence-accelerated Mice (SAMs) as a Model for Brain Aging and Immunosenescence

    PubMed Central

    Shimada, Atsuyoshi; Hasegawa-Ishii, Sanae

    2011-01-01

    The Senescence-Accelerated Mouse (SAM) represents a group of inbred mouse strains developed as a model for the study of human aging and age-related diseases. Senescence-prone (SAMP) strains exhibit an early onset of age-related decline in the peripheral immunity such as thymic involution, loss of CD4+ T cells, impaired helper T cell function, decreased antibody-forming capacity, dysfunction of antigen-presenting cells, decreased natural killer activity, increased auto-antibodies, and susceptibility to virus infection. Senescence-prone SAMP10 mice undergo age-related changes in the brain such as brain atrophy, shrinkage and loss of cortical neurons, retraction of cortical neuronal dendrites, loss of dendritic spines, loss of synapses, impaired learning and memory, depressive behavior, accumulation of neuronal DNA damage, neuronal ubiquitinated inclusions, reduced hippocampal cholinergic receptors, decreased neurotrophic factors, decreased hippocampal zinc and zinc transporters, increased sphyngomyelinase, and elevated oxidative-nitrative stress. Recent data indicating increased pro-inflammatory cytokines in the brain of SAMP10 mice are directing investigators toward an integration of immune and neural abnormalities to enhance understanding of the principles of brain aging. We highlight how mouse brain cells adopt cytokine-mediated responses and how SAMP10 mice are defective in these responses. SAMP10 model would be useful to study how age-related disturbances in peripheral immunity have an impact on dysregulation of brain tissue homeostasis, resulting in age-related neurodegeneration. PMID:22396891

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

    PubMed Central

    2016-01-01

    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

  10. Characterizing cognitive aging of working memory and executive function in animal models.

    PubMed

    Bizon, Jennifer L; Foster, Thomas C; Alexander, Gene E; Glisky, Elizabeth L

    2012-01-01

    Executive functions supported by prefrontal cortical (PFC) systems provide essential control and planning mechanisms to guide goal-directed behavior. As such, age-related alterations in executive functions can mediate profound and widespread deficits on a diverse array of neurocognitive processes. Many of the critical neuroanatomical and functional characteristics of prefrontal cortex are preserved in rodents, allowing for meaningful cross species comparisons relevant to the study of cognitive aging. In particular, as rodents lend themselves to genetic, cellular and biochemical approaches, rodent models of executive function stand to significantly contribute to our understanding of the critical neurobiological mechanisms that mediate decline of executive processes across the lifespan. Moreover, rodent analogs of executive functions that decline in human aging represent an essential component of a targeted, rational approach for developing and testing effective treatment and prevention therapies for age-related cognitive decline. This paper reviews behavioral approaches used to study executive function in rodents, with a focus on those assays that share a foundation in the psychological and neuroanatomical constructs important for human aging. A particular emphasis is placed on behavioral approaches used to assess working memory and cognitive flexibility, which are sensitive to decline with age across species and for which strong rodent models currently exist. In addition, other approaches in rodent behavior that have potential for providing analogs to functions that reliably decline to human aging (e.g., information processing speed) are discussed.

  11. Revisiting gerontology's scrapbook: from Metchnikoff to the Spectrum Model of Aging.

    PubMed

    Martin, Diane J; Gillen, Laura L

    2014-02-01

    The historical roots of gerontology date to a time when old age was characterized as physical and mental decline. Nonetheless, Metchnikoff questioned the inevitability of this decline, believing that quality of life could be improved by broadening our understanding of the science of aging, a multifaceted concept that extends well beyond the biological science interpretation so prevalent in gerontology's history. This article examines foundational gerontological theories in an effort to unravel complex interactions that constitute physiological aging processes, the psychological manifestations of individual adaptation, and the importance of social and spiritual relationships in aging successfully. Evaluating these theories through an interdisciplinary lens will benefit scholars, researchers, and aging services professionals because it offers opportunities to extend gerontological concepts from theory to development of models that can ultimately be applied in common practice to promote successful aging, regardless of one's physical or cognitive health status. To that end, we propose the Spectrum Model of Aging. Utilizing components of game theory, we believe it offers a synergistic approach to improving quality of later life and thus promises to move the field of gerontology beyond disciplinary boundaries.

  12. 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

  13. 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.

  14. Aging and percolation dynamics in a Non-Poissonian temporal network model

    NASA Astrophysics Data System (ADS)

    Moinet, Antoine; Starnini, Michele; Pastor-Satorras, Romualdo

    2016-08-01

    We present an exhaustive mathematical analysis of the recently proposed Non-Poissonian Activity Driven (NoPAD) model [Moinet et al., Phys. Rev. Lett. 114, 108701 (2015), 10.1103/PhysRevLett.114.108701], a temporal network model incorporating the empirically observed bursty nature of social interactions. We focus on the aging effects emerging from the non-Poissonian dynamics of link activation, and on their effects on the topological properties of time-integrated networks, such as the degree distribution. Analytic expressions for the degree distribution of integrated networks as a function of time are derived, exploring both limits of vanishing and strong aging. We also address the percolation process occurring on these temporal networks, by computing the threshold for the emergence of a giant connected component, highlighting the aging dependence. Our analytic predictions are checked by means of extensive numerical simulations of the NoPAD model.

  15. A constituent-based model of age-related changes in conduit arteries.

    PubMed

    Tsamis, Alkiviadis; Rachev, Alexander; Stergiopulos, Nikos

    2011-10-01

    In the present report, a constituent-based theoretical model of age-related changes in geometry and mechanical properties of conduit arteries is proposed. The model was based on the premise that given the time course of the load on an artery and the accumulation of advanced glycation end-products in the arterial tissue, the initial geometric dimensions and properties of the arterial tissue can be predicted by a solution of a boundary value problem for the governing equations that follow from finite elasticity, structure-based constitutive modeling within the constrained mixture theory, continuum damage theory, and global growth approach for stress-induced structure-based remodeling. An illustrative example of the age-related changes in geometry, structure, composition, and mechanical properties of a human thoracic aorta is considered. Model predictions were in good qualitative agreement with available experimental data in the literature. Limitations and perspectives for refining the model are discussed.

  16. Periodic and quasi-periodic behavior in resource-dependent age structured population models.

    PubMed

    Dilão, R; Domingos, T

    2001-03-01

    To describe the dynamics of a resource-dependent age structured population, a general non-linear Leslie type model is derived. The dependence on the resources is introduced through the death rates of the reproductive age classes. The conditions assumed in the derivation of the model are regularity and plausible limiting behaviors of the functions in the model. It is shown that the model dynamics restricted to its omega-limit sets is a diffeomorphism of a compact set, and the period-1 fixed points of the model are structurally stable. The loss of stability of the non-zero steady state occurs by a discrete Hopf bifurcation. Under general conditions, and after the loss of stability of the structurally stable steady states, the time evolution of population numbers is periodic or quasi-periodic. Numerical analysis with prototype functions has been performed, and the conditions leading to chaotic behavior in time are discussed.

  17. Modeling the durability of ZOSTAVAX® vaccine efficacy in people ≥60 years of age.

    PubMed

    Li, Xiaoming; Zhang, Jane H; Betts, Robert F; Morrison, Vicki A; Xu, Ruifeng; Itzler, Robbin F; Acosta, Camilo J; Dasbach, Erik J; Pellissier, James M; Johnson, Gary R; Chan, Ivan S F

    2015-03-17

    Since 2006, the vaccine, ZOSTAVAX(®), has been licensed to prevent herpes zoster. Only limited clinical follow-up data are available to evaluate duration of protection, an important consideration when developing HZ vaccination policy recommendations. Four Poisson regression models were developed based on an integrated analysis of data from the Shingles Prevention Study and its Short Term Persistence extension to estimate the effects of years-since-vaccination and chronological-age on vaccine efficacy among people ≥60 years old. The models included number of HZ cases parsed into categories by chronological-age and time-since-vaccination as the dependent variable with different explanatory variables in each model. In all models, the interaction between vaccine-group and chronological-age was statistically significant indicating that vaccine efficacy decreases with the expected effects of advancing age but the interaction between vaccine-group and time-since-vaccination was not statistically significant indicating that much of the reduction in vaccine efficacy over time-since-vaccination can be explained by increasing age.

  18. A structural model of age, grey matter volumes, education, and personality traits.

    PubMed

    Kitamura, Soichiro; Yasuno, Fumihiko; Yamamoto, Akihide; Kazui, Hiroaki; Kudo, Takashi; Matsuoka, Kiwamu; Kiuchi, Kuniaki; Kosaka, Jun; Nagatsuka, Kazuyuki; Iida, Hidehiro; Kishimoto, Toshifumi

    2016-01-01

    When the relationship between ageing and changes in personality traits is considered, it is important to know how they are influenced by biological and environmental factors. The present study examined the relationships between various factors associated with the effect of ageing on personality traits, including structural changes of the brain and environmental factors such as education. We recruited 41 healthy subjects. We administered the NEO Five-Factor Inventory to assess personality factors. Magnetic resonance imaging was performed, and regional grey matter (GM) volumes were obtained. We identified associations in the correlation analysis of age, cerebral GM volume, years of education, and the personality trait of openness. Path analysis was used to estimate the relationships among these factors. The path analysis model of age, GM volume, years of education, and the personality trait of openness revealed that age has an indirect negative association with openness through GM volume and years of education. Ageing was related to a decrease in GM volume, which was in turn related to a decrease in the openness score. Older subjects generally had fewer years of education, which was related to a lower openness score. Maintaining openness against the effects of ageing is desirable, and our results imply that interventions against age-related cerebral atrophy and the promotion of opportunities for higher education may contribute to the development and stability of a healthy personality during the adult life course. © 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.

  19. 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.

  20. The mare model for follicular maturation and reproductive aging in the woman.

    PubMed

    Carnevale, E M

    2008-01-01

    Reproductive aging and assisted reproduction are becoming progressively more relevant in human medicine. Research with human subjects is limited in many aspects, and consequently animal models may have considerable utility. Such models have provided insight into follicular function, oocyte maturation, and reproductive aging. However, models are often selected based on factors other than physiological or functional similarities. Although the mare has received limited attention as a model for reproduction in women, comparisons between these species indicate that the mare has many attributes of a good model. As the mare ages, cyclic and hormonal changes parallel those of older women. The initial sign of reproductive aging in both species is a shortening of the reproductive cycle with elevated concentrations of FSH. Subsequently, cycles become longer with intermittent ovulations and elevated concentrations of FSH and LH. Reproduction ceases with failure of follicular growth and elevated gonadotropins, apparently because of ovarian failure. In the older woman and mare, oocytes have been maintained in meiotic arrest for decades -- approximately four to five for the woman and two to three for the mare; in both species, reduced oocyte quality is the end factor identified in age-associated infertility. After induction of oocyte maturation in vivo, the timeline to ovulation is the same for the mare and woman, suggesting a comparable sequence of events. The mare's anatomy, long follicular phase and single dominant follicle provide a foundation for studies in oocyte and follicular development. The aim of this review is to evaluate the mare as an animal model to study age-associated changes in reproduction and to improve our understanding of oocyte and follicular maturation in vivo.

  1. AgedCare+GP: description and evaluation of an in-house model of general practice in a residential aged-care facility.

    PubMed

    Pain, Tilley; Stainkey, Lesley; Chapman, Sue

    2014-01-01

    This paper describes a medical model to provide in-house GP services to residents of aged-care facilities. Access to GP services for aged-care residents is decreasing, partially due to the changing demographic of the Australian GP workforce. The model we have developed is an in-house GP (AgedCare+GP) trialled in a publicly funded residential aged-care facility (RACF). The service model was based on the GP cooperative used in our after-hours general practice (AfterHours+GP). Briefly, the service model involves rostering a core group of GPs to provide weekly sessional clinics at the RACF. Financial contributions from appropriate Medicare Benefits Schedule (MBS) items for aged-care planning (including chronic conditions) provided adequate funds to operate the clinic for RACF residents. Evaluation of the service model used the number of resident transfers to the local emergency department as the primary outcome measure. There were 37 transfers of residents in the 3 months before the commencement of the AgedCare+GP and 11 transfers over a 3-month period at the end of the first year of operation; a reduction of almost 70%. This project demonstrates that AgedCare+GP is a successful model for GP service provision to RACF residents, and it also reduces the number of emergency department transfers.

  2. Ultra-long-range dynamic correlations in a microscopic model for aging gels

    NASA Astrophysics Data System (ADS)

    Chaudhuri, Pinaki; Berthier, Ludovic

    2017-06-01

    We use large-scale computer simulations to explore the nonequilibrium aging dynamics in a microscopic model for colloidal gels. We find that gelation resulting from a kinetically arrested phase separation is accompanied by "anomalous" particle dynamics revealed by superdiffusive particle motion and compressed exponential relaxation of time correlation functions. Spatiotemporal analysis of the dynamics reveals intermittent heterogeneities producing spatial correlations over extremely large length scales. Our study is a microscopically resolved model reproducing all features of the spontaneous aging dynamics observed experimentally in soft materials.

  3. Multiple morbidities in companion dogs: a novel model for investigating age-related disease

    PubMed Central

    Jin, Kelly; Hoffman, Jessica M.; Creevy, Kate E.; O’Neill, Dan G.; Promislow, Daniel E.L.

    2016-01-01

    The proportion of men and women surviving over 65 years has been steadily increasing over the last century. In their later years, many of these individuals are afflicted with multiple chronic conditions, placing increasing pressure on healthcare systems. The accumulation of multiple health problems with advanced age is well documented, yet the causes are poorly understood. Animal models have long been employed in attempts to elucidate these complex mechanisms with limited success. Recently, the domestic dog has been proposed as a promising model of human aging for several reasons. Mean lifespan shows twofold variation across dog breeds. In addition, dogs closely share the environments of their owners, and substantial veterinary resources are dedicated to comprehensive diagnosis of conditions in dogs. However, while dogs are therefore useful for studying multimorbidity, little is known about how aging influences the accumulation of multiple concurrent disease conditions across dog breeds. The current study examines how age, body weight, and breed contribute to variation in multimorbidity in over 2,000 companion dogs visiting private veterinary clinics in England. In common with humans, we find that the number of diagnoses increases significantly with age in dogs. However, we find no significant weight or breed effects on morbidity number. This surprising result reveals that while breeds may vary in their average longevity and causes of death, their age-related trajectories of morbidities differ little, suggesting that age of onset of disease may be the source of variation in lifespan across breeds. Future studies with increased sample sizes and longitudinal monitoring may help us discern more breed-specific patterns in morbidity. Overall, the large increase in multimorbidity seen with age in dogs mirrors that seen in humans and lends even more credence to the value of companion dogs as models for human morbidity and mortality. PMID:27876455

  4. 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

  5. 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

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

    PubMed Central

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

    1998-01-01

    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

  7. 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. © 2015 International Society for Neurochemistry.

  8. Advanced age diminishes tendon-to-bone healing in a rat model of rotator cuff repair.

    PubMed

    Plate, Johannes F; Brown, Philip J; Walters, Jordan; Clark, John A; Smith, Thomas L; Freehill, Michael T; Tuohy, Christopher J; Stitzel, Joel D; Mannava, Sandeep

    2014-04-01

    Advanced patient age is associated with recurrent tearing and failure of rotator cuff repairs clinically; however, basic science studies have not evaluated the influence of aging on tendon-to-bone healing after rotator cuff repair in an animal model. Hypothesis/ This study examined the effect of aging on tendon-to-bone healing in an established rat model of rotator cuff repair using the aged animal colony from the National Institute on Aging of the National Institutes of Health. The authors hypothesized that normal aging decreases biomechanical strength and histologic organization at the tendon-to-bone junction after acute repair. Controlled laboratory study. In 56 F344xBN rats, 28 old and 28 young (24 and 8 months of age, respectively), the supraspinatus tendon was transected and repaired. At 2 or 8 weeks after surgery, shoulder specimens underwent biomechanical testing to compare load-to-failure and load-relaxation response between age groups. Histologic sections of the tendon-to-bone interface were assessed with hematoxylin and eosin staining, and collagen fiber organization was assessed by semiquantitative analysis of picrosirius red birefringence under polarized light. Peak failure load was similar between young and old animals at 2 weeks after repair (31% vs 26% of age-matched uninjured controls, respectively; P > .05) but significantly higher in young animals compared with old animals 8 weeks after repair (86% vs 65% of age-matched uninjured controls, respectively; P < .01). Eight weeks after repair, fibroblasts appeared more organized and uniformly aligned in young animals on hematoxylin and eosin slides compared with old animals. Collagen birefringence analysis of the tendon-to-bone junction demonstrated that young animals had increased collagen fiber organization and similar histologic structure compared with age-matched controls (53.7 ± 2.4 gray scales; P > .05). In contrast, old animals had decreased collagen fiber organization and altered structure

  9. Efficient Workflows for Curation of Heterogeneous Data Supporting Modeling of U-Nb Alloy Aging

    SciTech Connect

    Ward, Logan Timothy; Hackenberg, Robert Errol

    2016-08-31

    These are slides from a presentation summarizing a graduate research associate's summer project. The following topics are covered in these slides: data challenges in materials, aging in U-Nb Alloys, Building an Aging Model, Different Phase Trans. in U-Nb, the Challenge, Storing Materials Data, Example Data Source, Organizing Data: What is a Schema?, What does a "XML Schema" look like?, Our Data Schema: Nice and Simple, Storing Data: Materials Data Curation System (MDCS), Problem with MDCS: Slow Data Entry, Getting Literature into MDCS, Staging Data in Excel Document, Final Result: MDCS Records, Analyzing Image Data, Process for Making TTT Diagram, Bottleneck Number 1: Image Analysis, Fitting a TTP Boundary, Fitting a TTP Curve: Comparable Results, How Does it Compare to Our Data?, Image Analysis Workflow, Curating Hardness Records, Hardness Data: Two Key Decisions, Before Peak Age? - Automation, Interactive Viz, Which Transformation?, Microstructure-Informed Model, Tracking the Entire Process, General Problem with Property Models, Pinyon: Toolkit for Managing Model Creation, Tracking Individual Decisions, Jupyter: Docs and Code in One File, Hardness Analysis Workflow, Workflow for Aging Models, and conclusions.

  10. 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.

  11. Frontiers of Model Animals for Neuroscience:Two Prosperous Aging Model Animals forPromoting Neuroscience Research

    PubMed Central

    Ito, Koichi

    2013-01-01

    A model animal showing spontaneous onset is a useful tool for investigating the mechanism of disease. Here, I would like to introduce two aging model animals expected to be useful for neuroscience research: the senescence-accelerated mouse (SAM) and the klotho mouse. The SAM was developed as a mouse showing a senescence-related phenotype such as a short lifespan or rapid advancement of senescence. In particular, SAMP8 and SAMP10 show age-related impairment of learning and memory. SAMP8 has spontaneous spongy degeneration in the brain stem and spinal cord with aging, and immunohistochemical studies reveal excess protein expression of amyloid precursor protein and amyloid β in the brain, indicating that SAMP8 is a model for Alzheimer’s disease. SAMP10 also shows age-related impairment of learning and memory, but it does not seem to correspond to Alzheimer’s disease because senile plaques primarily composed of amyloid β or neurofibrillary tangles primarily composed of phosphorylated tau were not observed. However, severe atrophy in the frontal cortex, entorhinal cortex, amygdala, and nucleus accumbens can be seen in this strain in an age-dependent manner, indicating that SAMP10 is a model for normal aging. The klotho mouse shows a phenotype, regulated by only one gene named α-klotho, similar to human progeria. The α-klotho gene is mainly expressed in the kidney and brain, and oxidative stress is involved in the deterioration of cognitive function of the klotho mouse. These animal models are potentially useful for neuroscience research now and in the near future. PMID:24172191

  12. Limiting extensibility constitutive model with distributed fibre orientations and ageing of abdominal aorta.

    PubMed

    Horný, Lukáš; Netušil, Marek; Daniel, Matěj

    2014-10-01

    The abdominal aorta is susceptible to age-related pathological changes (arteriosclerosis, atherosclerosis, aneurysm, and tortuosity). Computational biomechanics and mechanobiology provide models capable of predicting mutual interactions between a changing mechanical environment and patho-physiological processes in ageing. However, a key factor is a constitutive equation which should reflect the internal tissue architecture. Our study investigates three microstructurally-motivated invariant-based hyperelastic anisotropic models suitable for description of the passive mechanical behaviour of the human abdominal aorta at a multiaxial state of stress known from recent literature. The three adopted models have also been supplemented with a newly proposed constitutive model (limiting extensibility with fibre dispersion). All models additively decouple the mechanical response of the isotropic (elastin and smooth muscle cells represented by the neo-Hookean term) and the anisotropic (collagen) parts. Two models use exponential functions to capture large strain stiffening ascribed to the engagement of collagen fibres into the load-bearing process. The other two models are based on the concept of limiting extensibility. Perfect alignment of reinforcing fibres with two preferred directions as well as fibre dispersion are considered. Constitutive models are calibrated to the inflation-extension response adopted from the literature based on the computational model of the residually-stressed thick-walled tube. A correlation analysis of determined material parameters was performed to reveal dependence on the age. The results of the nonlinear regression suggest that limiting fibre extensibility is the concept which is suitable to be used for the constitutive description of the aorta at multiaxial stress states and is highly sensitive to ageing-induced changes in mechanical response.

  13. 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. (c) 2015 APA, all rights reserved).

  14. Rhyacian A-type tholeiitic granites in southern Brazil: Geochemistry, U-Pb zircon ages and Nd model ages

    NASA Astrophysics Data System (ADS)

    Mesquita, Maria José; Bitencourt, Maria de Fátima; Nardi, Lauro Stoll; Picanço, Jefferson; Chemale, Farid, Jr.; Pimenta, Vanessa de Almeida

    2017-04-01

    In the southern South American platform, 2.5 to 2.0 Ga terranes, probably related to the Atlantica supercontinent, occur mainly as minor reworked inliers within Neoproterozoic, Brasiliano/Pan-African orogenic belts, as the Ribeira Belt in southern Brazil. The dispersion of such fragments has generated uncertainties about their geotectonic reconstruction, and their study has been supported mainly by elemental and isotope geochemistry. The southern Ribeira Belt lies between the Paranapanema and Luiz Alves cratons and contains reworked Neoarquean and Paleoproterozoic terranes which outcrop as basement nuclei in supracrustal sequences, as the Setuva Complex. The Água Comprida Suite, situated in the northern part of the Setuva Complex, consists of Amphibole-Biotite Syenogranite (ABS), Porphyritic Biotite Syenogranite (PBS), and Equigranular Biotite Syenogranite (EBS). All granites are foliated and intensively deformed. The oldest foliation (Sn) is marked by augen feldspars set in a recrystallized matrix, followed by a crenulation cleavage (Sn+1) which evolves to discrete shear zones. ABS is a metaluminous, reduced A-type granite with FeOt / (FeOt + MgO) > 0.9, with high HFSE and REE contents, corresponding to magmas related to continental medium to high-K tholeiitic series. PBS and specially EBS are highly differentiated, metaluminous to peraluminous (EBS), oxidized granites. The increase of Al2O3 and Rb, and decrease of HFS and RE elements relative to ABS indicate their evolution from tholeiitic magmas. The Água Comprida Suite granites are cogenetic rocks evolved from a within-plate mantle source, marked by high Nb, Ta, and Y. The influence of previously metasomatised mantle sources is evidenced by negative Nb, Ti, and P anomalies. The age of ABS is 2187 ± 26 Ma, and that of PBS is between 2180 ± 13 to 2186 ± 22 Ma. The Nd model age of 2.4 Ga, and ɛNd(2.18 Ga) between - 0.23 and - 0.27 support the interpretation of ABS being formed from juvenile material with a

  15. 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.

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

    PubMed

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

    2015-09-01

    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 months-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.

  17. Effects of age, gender, and gonadectomy on neurochemistry and behavior in animal models of Parkinson's disease.

    PubMed

    Tamás, Andrea; Lubics, Andrea; Lengvári, István; Reglodi, Dóra

    2006-04-01

    The effects of aging and gender on the neurochemistry of the dopaminergic system have been studied extensively; however, data on comparative behavioral consequences of lesions of the dopaminergic system in aging and in female animals are limited. This study presents experimental results on the behavioral and morphological outcome in young, aging, and gonadectomized male and female rats in the 6-OHDA model of Parkinson's disease. Both young and aging male animals were more susceptible to 6-OHDA than females: female rats had significantly less dopaminergic cell loss and showed a higher degree of behavioral recovery. Although the dopaminergic cell loss was only slightly more in the aging rats of the same sex, they showed more severe behavioral deficits in both gender groups. Ovariectomy did not significantly influence the dopaminergic cell loss, but behavioral recovery was worse when compared to non-ovariectomized females. In contrast, castrated males had significantly less dopaminergic cell loss than non-castrated males, but the behavioral recovery was not significantly better. The obtained results are discussed in light of the available literature on the age and gender differences in animals models of Parkinson's disease.

  18. Global stability of a multi-group model with vaccination age, distributed delay and random perturbation.

    PubMed

    Xu, Jinhu; Zhou, Yicang

    2015-10-01

    A multi-group epidemic model with distributed delay and vaccination age has been formulated and studied. Mathematical analysis shows that the global dynamics of the model is determined by the basic reproduction number R0: the disease-free equilibrium is globally asymptotically stable if R0 ≤ 1, and the endemic equilibrium is globally asymptotically stable if R0 > 1. Lyapunov functionals are constructed by the non-negative matrix theory and a novel grouping technique to establish the global stability. The stochastic perturbation of the model is studied and it is proved that the endemic equilibrium of the stochastic model is stochastically asymptotically stable in the large under certain conditions.

  19. Renal Pathology in a Nontraditional Aging Model: The Naked Mole-Rat (Heterocephalus glaber).

    PubMed

    Delaney, M A; Kinsel, M J; Treuting, P M

    2016-03-01

    The naked mole-rat (NMR; Heterocephalus glaber) is growing in popularity as a model for aging research due to its extreme longevity (up to 30 years), highly adapted physiology, and resistance to cancer, particularly when compared with traditional aging models such as laboratory mice and rats. Despite the NMR's seemingly lengthy health span, several age-related lesions have been documented. During a 15-year retrospective evaluation of a zoo-housed population, histologic changes in the kidneys were reported in 127 of 138 (92%) adult NMRs. Of these, renal tubular mineralization was very common (115 of 127; 90.6%) and found in NMRs without concurrent renal lesions (36 of 127; 28.3%). Many of the other described lesions were considered progressive stages of a single process, generally referred to as chronic nephritis or nephropathy, and diagnosed in 73 of 127 (57.5%), while end-stage renal disease was reported in only 12 (9.4%) NMRs. Renal lesions of these NMRs were comparable to disease entities reported in laboratory rats and certain strains of inbred and noninbred mice. Although many lesions of NMR kidneys were similar to those found in aged laboratory rodents, some common urinary diseases were not represented in the examined colonies. The goal of this study was to describe renal lesions in NMRs from a zoologic setting to familiarize investigators and pathologists with an apparently common and presumably age-related disease in this nontraditional model. © The Author(s) 2015.

  20. 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

  1. 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

  2. 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.

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

    DOE PAGES

    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

  4. 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

  5. A model of cognitive decline and suicidal ideation in adults aging with HIV.

    PubMed

    Vance, David E; Ross, Jill A; Moneyham, Linda; Farr, Kenneth F; Fordham, Pam

    2010-06-01

    The number of older adults with HIV continues to grow primarily because of the effectiveness of highly active antiretroviral therapy. Despite this welcomed benefit from pharmaceutical advances, aging with this disease presents an entirely new set of problems. The combination of aging and HIV can create a variety of stressors that may weaken one's resolve and further debilitate already compromised cognitive systems, which may increase rates of depression, suicidal ideation, and suicide. Studies indicate that older adults with HIV experience higher levels of depression and suicidal ideation than other older adults do or than younger adults with HIV do. Cognitive declines associated with both HIV and aging may provide insight into this phenomenon. A model of cognitive decline and suicidal ideation in adults aging with HIV is provided. Implications for nursing practice and research are discussed.

  6. Weak temperature dependence of ageing of structural properties in atomistic model glassformers

    NASA Astrophysics Data System (ADS)

    Jenkinson, Thomas; Crowther, Peter; Turci, Francesco; Royall, C. Patrick

    2017-08-01

    Ageing phenomena are investigated from a structural perspective in two binary Lennard-Jones glassformers, the Kob-Andersen and Wahnström mixtures. In both, the geometric motif assumed by the glassformer upon supercooling, the locally favoured structure (LFS), has been established. The Kob-Andersen mixture forms bicapped square antiprisms; the Wahnström model forms icosahedra. Upon ageing, we find that the structural relaxation time has a time-dependence consistent with a power law. However, the LFS population and potential energy increase and decrease, respectively, in a logarithmic fashion. Remarkably, over the time scales investigated, which correspond to a factor of 104 change in relaxation times, the rate at which these quantities age appears almost independent of temperature. Only at temperatures far below the Vogel-Fulcher-Tamman temperature do the ageing dynamics slow.

  7. 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

  8. 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.

  9. Aged garlic extract and S-allylcysteine prevent apoptotic cell death in a chemical hypoxia model.

    PubMed

    Orozco-Ibarra, Marisol; Muñoz-Sánchez, Jorge; Zavala-Medina, Martín E; Pineda, Benjamín; Magaña-Maldonado, Roxana; Vázquez-Contreras, Edgar; Maldonado, Perla D; Pedraza-Chaverri, José; Chánez-Cárdenas, María Elena

    2016-02-01

    Aged garlic extract (AGE) and its main constituent S-allylcysteine (SAC) are natural antioxidants with protective effects against cerebral ischemia or cancer, events that involve hypoxia stress. Cobalt chloride (CoCl2) has been used to mimic hypoxic conditions through the stabilization of the α subunit of hypoxia inducible factor (HIF-1α) and up-regulation of HIF-1α-dependent genes as well as activation of hypoxic conditions such as reactive oxygen species (ROS) generation, loss of mitochondrial membrane potential and apoptosis. The present study was designed to assess the effect of AGE and SAC on the CoCl2-chemical hypoxia model in PC12 cells. We found that CoCl2 induced the stabilization of HIF-1α and its nuclear localization. CoCl2 produced ROS and apoptotic cell death that depended on hypoxia extent. The treatment with AGE and SAC decreased ROS and protected against CoCl2-induced apoptotic cell death which depended on the CoCl2 concentration and incubation time. SAC or AGE decreased the number of cells in the early and late stages of apoptosis. Interestingly, this protective effect was associated with attenuation in HIF-1α stabilization, activity not previously reported for AGE and SAC. Obtained results show that AGE and SAC decreased apoptotic CoCl2-induced cell death. This protection occurs by affecting the activity of HIF-1α and supports the use of these natural compounds as a therapeutic alternative for hypoxic conditions.

  10. 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

  11. Effect of age on sperm fertility potential: oocyte donation as a model.

    PubMed

    Gallardo, E; Simón, C; Levy, M; Guanes, P P; Remohí, J; Pellicer, A

    1996-08-01

    To determine the effect of age on sperm fecundability using oocyte donation as an in vivo model. Oocyte donation and IVF programs at the Instituto Valenciano de Infertilidad. Retrospective study in which four groups of oocyte donation cycles were established according to age of the male providing the semen sample: group 1 (n = 31) < 30 years; group 2 (n = 195) 31 to 40 years; group 3 (n = 98) 41 to 50 years; group 4 (n = 21) > 51 years, the oldest being 64 years. All donated oocytes were obtained from patients < 35 years old. Male age, sperm characteristics (volume, concentration, motility, morphology), fertilization, embryo quality, pregnancy, implantation, and abortion rates among recipients. Similar sperm characteristics in fresh as well as after preparation for IVF were observed among males of different ages. Fertilization, embryo quality, pregnancy, and implantation were similar among the established groups. The mean age of the females included in each group significantly increased from group 1 to group 4. Age (up to 64 years) does not affect sperm characteristics or its ability to fertilize human eggs. Similarly, embryo development in vitro as well as implantation in recipient uteri are not affected by age of the male providing the semen sample.

  12. Neurogenesis in a rat model of age-related cognitive decline.

    PubMed

    Bizon, J L; Lee, H J; Gallagher, M

    2004-08-01

    Age-related decrements in hippocampal neurogenesis have been suggested as a basis for learning impairment during aging. In the current study, a rodent model of age-related cognitive decline was used to evaluate neurogenesis in relation to hippocampal function. New hippocampal cell survival was assessed approximately 1 month after a series of intraperitoneal injections of 5-bromo-2'-deoxyuridine (BrdU). Correlational analyses between individual measures of BrdU-positive cells and performance on the Morris water maze task provided no indication that this measure of neurogenesis was more preserved in aged rats with intact cognitive abilities. On the contrary, among aged rats, higher numbers of BrdU-positive cells in the granule cell layer were associated with a greater degree of impairment on the learning task. Double-labelling studies confirmed that the majority of the BrdU+ cells were of the neuronal phenotype; the proportion of differentiated neurons was not different across a broad range of cognitive abilities. These data demonstrate that aged rats that maintain cognitive function do so despite pronounced reductions in hippocampal neurogenesis. In addition, these findings suggest the interesting possibility that impaired hippocampal function is associated with greater survival of newly generated hippocampal neurons at advanced ages.

  13. Random regression model of growth during the first three months of age in Spanish Merino sheep.

    PubMed

    Molina, A; Menéndez-Buxadera, A; Valera, M; Serradilla, J M

    2007-11-01

    A total of 88,727 individual BW records of Spanish Merino lambs, obtained from 30,214 animals between 2 and 92 d of age, were analyzed using a random regression model (RRM). These animals were progeny of 546 rams and 15,586 ewes raised in 30 flocks, between 1992 and 2002, with a total of 45,941 animals in the pedigree. The contemporary groups (animals of the same flock, year, and season, with 452 levels), the lambing number (11 levels), the combination sex of lambs with type of litter (4 levels), and a fixed regression coefficient of age on BW were included as fixed effects. A total of 7 RRM were compared, and the best fit was obtained for a model of order 3 for the direct and maternal genetic effects and for the individual permanent environmental effect. For the maternal permanent environmental effect the best model had an order 2. The residual variance was assumed to be heterogeneous with 10 age classes; the covariance between both genetic effects was included. According to the results of the selected RRM, the heritability for both genetic effects (h(a)2 and h(m)2) increased with age, with estimates of 0.123 to 0.186 for h(a)2 and of 0.059 to 0.108 for h(m)2. The correlations between direct and genetic maternal effects were -0.619 to -0.387 during the first 45 d of age and decreased as age increased, until reaching values from -0.366 to -0.275 between 45 to 75 d of age. Important changes in ranking of the animals were found based on the breeding value estimation with the current method and with the random regression procedure. The use of RRM to analyze the genetic trajectory of growth in this population of Merino sheep is highly recommended.

  14. Modelling in vivo skeletal muscle ageing in vitro using three-dimensional bioengineered constructs.

    PubMed

    Sharples, Adam P; Player, Darren J; Martin, Neil R W; Mudera, Vivek; Stewart, Claire E; Lewis, Mark P

    2012-12-01

    Degeneration of skeletal muscle (SkM) with age (sarcopenia) is a major contributor to functional decline, morbidity and mortality. Methodological implications often make it difficult to embark on interventions in already frail and diseased elderly individuals. Using in vitro three-dimensional (3D) bioengineered skeletal muscle constructs that model aged phenotypes and incorporate a representative extracellular matrix (collagen), are under tension, and display morphological and transcript expression of mature skeletal muscle may more accurately characterize the SkM niche. Furthermore, an in vitro model would provide greater experimental manipulation with regard to gene, pharmacological and exercise (mechanical stretch/electrical stimulation) therapies and thus strategies for combating muscle wasting with age. The present study utilized multiple population-doubled (MPD) murine myoblasts compared with parental controls (CON), previously shown to have an aged phenotype in monolayer cultures (Sharples et al., 2011), seeded into 3D type I collagen matrices under uniaxial tension. 3D bioengineered constructs incorporating MPD cells had reduced myotube size and diameter vs. CON constructs. MPD constructs were characterized by reduced peak force development over 24 h after cell seeding, reduced transcript expression of remodelling matrix metalloproteinases, MMP2 and MMP9, with reduced differentiation/hypertrophic potential shown by reduced IGF-I, IGF-IR, IGF-IEa, MGF mRNA. Increased IGFBP2 and myostatin in MPD vs. CON constructs also suggested impaired differentiation/reduced regenerative potential. Overall, 3D bioengineered skeletal muscle constructs represent an in vitro model of the in vivo cell niche with MPD constructs displaying similar characteristics to ageing/atrophied muscle in vivo, thus potentially providing a future test bed for therapeutic interventions to contest muscle degeneration with age. © 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd

  15. Age at first birth and fathers' subsequent health: evidence from sibling and twin models.

    PubMed

    Pudrovska, Tetyana; Carr, Deborah

    2009-06-01

    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.

  16. 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.

  17. Age and regulatory focus determine preferences for health-related role models.

    PubMed

    Lockwood, Penelope; Chasteen, Alison L; Wong, Carol

    2005-09-01

    The authors hypothesized that the effectiveness of role models varies across the adult life span because of differences in health-related regulatory orientations. Because young adults have strong health-related promotion orientations, they should be motivated by positive models who illustrate the benefits of good health. Because older adults have more balanced health-related promotion and prevention orientations, they should be motivated not only by positive models but also by negative models who illustrate the costs of poor health. Results indicated that both young and older adults perceived positive models to be motivating, but older adults found negative models to be more motivating than did young adults. Age differences in responses to negative models were partially mediated by differences in health-related prevention orientation.

  18. Improving age-depth models using sedimentary proxies for accumulation rates in fluvio-lacustrine deposits

    NASA Astrophysics Data System (ADS)

    Minderhoud, Philip S. J.; Cohen, Kim M.; Toonen, Willem. H. J.; Erkens, Gilles; Hoek, Wim Z.

    2017-04-01

    Lacustrine fills, including those of oxbow lakes in river floodplains, often hold valuable sedimentary and biological proxy records of palaeo-environmental change. Precise dating of accumulated sediments at levels throughout these records is crucial for interpretation and correlation of (proxy) data existing within the fills. Typically, dates are gathered from multiple sampled levels and their results are combined in age-depth models to estimate the ages of events identified between the datings. In this paper, a method of age-depth modelling is presented that varies the vertical accumulation rate of the lake fill based on continuous sedimentary data. In between Bayesian calibrated radiocarbon dates, this produces a modified non-linear age-depth relation based on sedimentology rather than linear or spline interpolation. The method is showcased on a core of an infilled palaeomeander at the floodplain edge of the river Rhine near Rheinberg (Germany). The sequence spans from 4.7 to 2.9 ka cal BP and consists of 5.5 meters of laminated lacustrine, organo-clastic mud, covered by 1 meter of peaty clay. Four radiocarbon dates provide direct dating control, mapping and dating in the wider surroundings provide additional control. The laminated, organo-clastic facies of the oxbow fill contains a record of nearby fluvial-geomorphological activity, including meander reconfiguration events and passage of rare large floods, recognized as fluctuations in coarseness and amount of allochthonous clastic sediment input. Continuous along-core sampling and measurement of loss-on-ignition (LOI) provided a fast way of expressing the variation in clastic sedimentation influx from the nearby river versus autochthonous organic deposition derived from biogenic production in the lake itself. This low-cost sedimentary proxy data feeds into the age-depth modelling. The sedimentology-modelled age-depth relation (re)produces the distinct lithological boundaries in the fill as marked changes in

  19. Increased ghrelin signaling prolongs survival in mouse models of human aging through activation of sirtuin1

    PubMed Central

    Fujitsuka, N; Asakawa, A; Morinaga, A; Amitani, M S; Amitani, H; Katsuura, G; Sawada, Y; Sudo, Y; Uezono, Y; Mochiki, E; Sakata, I; Sakai, T; Hanazaki, K; Yada, T; Yakabi, K; Sakuma, E; Ueki, T; Niijima, A; Nakagawa, K; Okubo, N; Takeda, H; Asaka, M; Inui, A

    2016-01-01

    Caloric restriction (CR) is known to retard aging and delay functional decline as well as the onset of diseases in most organisms. Ghrelin is secreted from the stomach in response to CR and regulates energy metabolism. We hypothesized that in CR ghrelin has a role in protecting aging-related diseases. We examined the physiological mechanisms underlying the ghrelin system during the aging process in three mouse strains with different genetic and biochemical backgrounds as animal models of accelerated or normal human aging. The elevated plasma ghrelin concentration was observed in both klotho-deficient and senescence-accelerated mouse prone/8 (SAMP8) mice. Ghrelin treatment failed to stimulate appetite and prolong survival in klotho-deficient mice, suggesting the existence of ghrelin resistance in the process of aging. However, ghrelin antagonist hastened death and ghrelin signaling potentiators rikkunshito and atractylodin ameliorated several age-related diseases with decreased microglial activation in the brain and prolonged survival in klotho-deficient, SAMP8 and aged ICR mice. In vitro experiments, the elevated sirtuin1 (SIRT1) activity and protein expression through the cAMP–CREB pathway was observed after ghrelin and ghrelin potentiator treatment in ghrelin receptor 1a-expressing cells and human umbilical vein endothelial cells. Furthermore, rikkunshito increased hypothalamic SIRT1 activity and SIRT1 protein expression of the heart in the all three mouse models of aging. Pericarditis, myocardial calcification and atrophy of myocardial and muscle fiber were improved by treatment with rikkunshito. Ghrelin signaling may represent one of the mechanisms activated by CR, and potentiating ghrelin signaling may be useful to extend health and lifespan. PMID:26830139

  20. Age at Marriage as a Mobility Contingency: Estimates for the Nye-Berardo Model

    ERIC Educational Resources Information Center

    Call, Vaughn R. A.; Otto, Luther B.

    1977-01-01

    This study provides estimates for the Nye and Berardo model of the effect of age at marriage on socioeconomic attainments. The major findings are that marital timing has neither a total effect on educational and occupational attainments, nor does it mediate the total effects of family socioeconomic statuses. (Author)

  1. Individual tree growth models for natural even-aged shortleaf pine

    Treesearch

    Chakra B. Budhathoki; Thomas B. Lynch; James M. Guldin

    2006-01-01

    Shortleaf pine (Pinus echinata Mill.) measurements were available from permanent plots established in even-aged stands of the Ouachita Mountains for studying growth. Annual basal area growth was modeled with a least-squares nonlinear regression method utilizing three measurements. The analysis showed that the parameter estimates were in agreement...

  2. Crisis Model for Older Adults: Special Considerations for an Aging Population

    ERIC Educational Resources Information Center

    Jungers, Christin M.; Slagel, Leslie

    2009-01-01

    As the U.S. population ages, counselors must begin structuring their interactions to meet the unique needs of older adults, especially in the area of crisis intervention. The purposes of this article are to draw attention to the rapidly growing, often disregarded older population and to introduce the Crisis Model for Older Adults (CM-OA), an…

  3. 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...

  4. Modeling the aging heart: from local respiratory defects to global rhythm disturbances.

    PubMed

    Khrapko, Konstantin; Trayanova, Natalia; Nattel, Stanley

    2015-05-05

    In this issue, Baris et al. (2015) describe cardiac rhythm abnormalities in a mouse model of mitochondrial dysfunction in widely distributed cells of the aging human heart. How do a few metabolically challenged cells disrupt cardiac rhythm? We suggest that these cells provide "crystallization centers" for latent dysfunctional zones to allow arrhythmia emergence.

  5. Invariance of an Extended Technology Acceptance Model Across Gender and Age Group

    ERIC Educational Resources Information Center

    Ahmad, Tunku Badariah Tunku; Madarsha, Kamal Basha; Zainuddin, Ahmad Marzuki; Ismail, Nik Ahmad Hisham; Khairani, Ahmad Zamri; Nordin, Mohamad Sahari

    2011-01-01

    In this study, we examined the likelihood of a TAME (extended technology acceptance model), in which the interrelationships among computer self-efficacy, perceived usefulness, intention to use and self-reported use of computer-mediated technology were tested. In addition, the gender- and age-invariant of its causal structure were evaluated. The…

  6. 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...

  7. 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…

  8. On the Problem of the Numerical Model Construction of Zero-Age Substars

    NASA Astrophysics Data System (ADS)

    Zakhozhaj, V. A.; Blokhina, M. D.; Pysarenko, A. I.; Yatsenko, A. A.; Slusarenko, Yu. V.

    The numerical modelling of substars inner structure is analysed and main definitions are suggested. Here we present results of calculation of degeneracy parameter psi, permitting to make calculate the dependence of number of free electrons on function temperature and density typical interior of zero-age substars (ZAS).

  9. 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…

  10. 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

  11. Rowe and Kahn's Model of Successful Aging Revisited: Positive Spirituality--The Forgotten Factor.

    ERIC Educational Resources Information Center

    Crowther, Martha R.; Parker, Michael W.; Achenbaum, W. A.; Larimore, Walter L.; Koenig, Harold G.

    2002-01-01

    Explains the concept of positive spirituality and offers evidence that links positive spirituality with health. Describes effective partnerships between health professionals and religious communities and summarized the information as a basis for strengthening the existing successful aging model proposed by Rowe and Kahn. (Contains 59 references…

  12. Education for Positive Ageing: A Partnership Model for Effecting Sustainable Outcomes.

    ERIC Educational Resources Information Center

    Feldman, Susan; Mahoney, Helen; Seedsman, Terence

    2002-01-01

    Pre/posttest results from 282 elementary students who interacted with older adults and observations by teachers and elders revealed changes in attitudes and awareness about aging. In stage 2, preservice teachers and older adults worked together in elementary schools. A model for sustainable lifespan curriculum involving elementary schools, teacher…

  13. Modelling cell lifespan and proliferation: is likelihood to die or to divide independent of age?

    PubMed Central

    Dowling, Mark R; Milutinović, Dejan; Hodgkin, Philip D

    2005-01-01

    In cell lifespan studies the exponential nature of cell survival curves is often interpreted as showing the rate of death is independent of the age of the cells within the population. Here we present an alternative model where cells that die are replaced and the age and lifespan of the population pool is monitored until a steady state is reached. In our model newly generated individual cells are given a determined lifespan drawn from a number of known distributions including the lognormal, which is frequently found in nature. For lognormal lifespans the analytic steady-state survival curve obtained can be well-fit by a single or double exponential, depending on the mean and standard deviation. Thus, experimental evidence for exponential lifespans of one and/or two populations cannot be taken as definitive evidence for time and age independence of cell survival. A related model for a dividing population in steady state is also developed. We propose that the common adoption of age-independent, constant rates of change in biological modelling may be responsible for significant errors, both of interpretation and of mathematical deduction. We suggest that additional mathematical and experimental methods must be used to resolve the relationship between time and behavioural changes by cells that are predominantly unsynchronized. PMID:16849210

  14. A Second Note on Ageing in a Library Circulation Model: The Correlation Structure.

    ERIC Educational Resources Information Center

    Burrell, Quentin L.

    1986-01-01

    Correlation structure of the Burrell and Cane mixed Poisson model for library loans with aging is presented and illustrated by data from University of Sussex. The approach is compared and contrasted with that originally formulated by Morse and recently reevaluated by Beheshti and Tague. Directions for future investigations are suggested. (Author)

  15. 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…

  16. Structural equation models of memory performance across noise conditions and age groups.

    PubMed

    Enmarker, Ingela; Boman, Eva; Hygge, Staffan

    2006-12-01

    Competing models of declarative memory were tested with structural equation models to analyze whether a second-order latent variable structure for episodic and semantic memory was invariant across age groups and across noise exposure conditions. Data were taken from three previous experimental noise studies that were performed with the same design, procedure, and dependent measures, and with participants from four age groups (13-14, 18-20, 35-45, and 55-65 years). Two noise conditions, road traffic noise and meaningful irrelevant speech, were compared to a quiet control group. The structural models put to the test were taken from Nyberg et al. (2003), which employed several memory tests that were the same as ours and studied age-groups that partly overlapped with our groups. In addition we also varied noise exposure conditions. Our analyses replicated and supported the second-order semantic-episodic memory models in Nyberg et al. (2003). The latent variable structures were invariant across age groups, with the exception of our youngest group, which by itself showed a less clear latent structure. The obtained structures were also invariant across noise exposure conditions. We also noted that our text memory items, which did not have a counterpart in the study by Nyberg et al. (2003), tend to form a separate latent variable loading on episodic memory.

  17. A homeostatic model of oxidative damage explains paradoxes observed in earlier aging experiments: a fusion and extension of older theories of aging.

    PubMed

    Novoseltsev, V N; Novoseltseva, J; Yashin, A I

    2001-01-01

    The Rate of Living and the Threshold Theories of Aging are two contradicting approaches used to explain experimental facts about aging in fruit flies. In this paper we suggest an approach that unifies these theories and removes the contradiction. The approach involves quantitative description of the oxidative stress theory of aging, which is presented in the form of a mathematical homeostatic model. The crucial variable in the model is called 'homeostatic capacity', which is analogous to the classical notion of vitality. We model the process of aging as the age-related accumulation of damage produced by oxidative stress, which reduces the homeostatic capacity of the organism. The model is tested with the experimental data obtained in the classical experiments by Maynard Smith in 1958-1963. Our homeostatic model explains the well-known results of these experiments more accurate than any one of the early theories of aging. We form an hypothesis about the mechanisms underlying the results observed in the experiments and analyze a possible interplay of these mechanisms. Our virtual replication of Maynard Smith's classical experiments demonstrates that mathematical modeling can be a powerful tool to reveal and investigate the inherent genetic and physiological processes underlying the data observed in complicated insect experiments.

  18. 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.

  19. Experimental models for aging and their potential for novel drug discovery.

    PubMed

    Folch, Jaume; Busquets, Oriol; Sánchez-López, Miren EttchetoElena; Pallàs, Mercè; Beas-Zarate, Carlos; Marin, Miguel; Casadesus, Gemma; Olloquequi, Jordi; Auladell, Carme; Camins, Antoni

    2017-07-07

    The development of antiaging drugs is an interesting area of scientific research. In order to evaluate the beneficial effects of new potential drugs, it is necessary to gather the specific knowledge on the adequate preclinical models that are available. This review focuses on invertebrate and vertebrate preclinical models used to evaluate the efficacy of antiaging compounds, with the objective to extend lifespan and health span. Dietary restriction (DR), a common experimental process to extend lifespan in all organisms, is also discussed. Besides, classical antiaging drugs such as resveratrol, rapamycin and metformin, denominated DR mimetics, are reviewed. The main therapeutic targets of these drugs include sirtuins, IGF-1, and mTOR, all of them being modulated by DR. The National Institute on Aging (NIA) developed the Interventions Testing Program (ITP). At the preclinical level, the ITP uses genetically heterogeneous mice model (HET), which is probably the most suitable rodent model to study potential drugs preventing aging-related diseases. The accelerated-senescence mouse P8 is also an interesting rodent model for the research in the field of aging. Notwithstanding, non-human primates are still necessary prior to clinical trials, since they allow an easier extrapolation to humans due to their anatomical and physiological similarities. In this review, the different models and approaches for antiaging studies were evaluated. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. 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.

  1. 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

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

    PubMed

    O'Neil, Sean F; Mac, Amy; Rhodes, Gillian; Webster, Michael A

    2015-12-01

    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.

  3. 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

  4. Effect of aging on airway remodeling and muscarinic receptors in a murine acute asthma model

    PubMed Central

    Kang, Ji Young; Lee, Sook Young; Rhee, Chin Kook; Kim, Seung Joon; Kwon, Soon Seog; Kim, Young Kyoon

    2013-01-01

    Background and objectives The influence of aging on the development of asthma has not been studied thoroughly. The aim of this study was to investigate age-related airway responses involving lung histology and expression of muscarinic receptors in a murine model of acute asthma. Methods Female BALB/c mice at the ages of 6 weeks and 6, 9, and 12 months were sensitized and challenged with ovalbumin (OVA) for 1 month (n = 8–12 per group). We analyzed inflammatory cells and T-helper (Th)2 cytokines in bronchoalveolar lavage (BAL) fluid and parameters of airway remodeling and expression of muscarinic receptors in lung tissue. Results Among the OVA groups, total cell and eosinophil numbers in BAL fluid were significantly higher in the older (6-, 9-, and 12-month-old) mice than in the young (6-week-old) mice. Interleukin (IL) 4 (IL-4) concentration increased, but IL-5 and IL-13 concentrations showed a decreased tendency, with age. IL-17 concentration tended to increase with age, which did not reach statistical significance. Periodic acid-Schiff (PAS) staining area, peribronchial collagen deposition, and area of α-smooth muscle staining were significantly higher in the 6-month older OVA group than in the young OVA group. The expression of the M3 and M2 muscarinic receptors tended to increase and decrease, respectively, with age. Conclusion The aged mice showed an active and unique pattern not only on airway inflammation, but also on airway remodeling and expression of the muscarinic receptors during the development of acute asthma compared with the young mice. These findings suggest that the aging process affects the pathogenesis of acute asthma and age-specific approach might be more appropriate for better asthma control in a clinical practice. PMID:24204129

  5. Predicting Age-Appropriate Pharmacokinetics of Six Volatile Organic Compounds in the Rat Utilizing Physiologically Based Pharmacokinetic Modeling

    EPA Science Inventory

    The capability of physiologically based pharmacokinetic models to incorporate age-appropriate physiological and chemical-specific parameters was utilized to predict changes in internal dosimetry for six volatile organic compounds (VOCs) across different ages of rats.

  6. Predicting Age-Appropriate Pharmacokinetics of Six Volatile Organic Compounds in the Rat Utilizing Physiologically Based Pharmacokinetic Modeling

    EPA Science Inventory

    The capability of physiologically based pharmacokinetic models to incorporate age-appropriate physiological and chemical-specific parameters was utilized to predict changes in internal dosimetry for six volatile organic compounds (VOCs) across different ages of rats.

  7. Modeling the Multiday Evolution and Aging of Secondary Organic Aerosol During MILAGRO 2006

    NASA Astrophysics Data System (ADS)

    Dzepina, K.; Cappa, C. D.; Volkamer, R.; Madronich, S.; Decarlo, P. F.; Zaveri, R. A.; Jimenez, J. L.

    2010-12-01

    In this study we apply several recently-proposed models to the evolution of secondary organic aerosols (SOA) and organic gases advected from downtown Mexico City at an altitude of ~3.5 km during three days of aging. We constrain the model with and compare its results to available observations. The model SOA formed from oxidation of volatile organic compounds (V-SOA) alone cannot explain the observed mass loadings in aged pollution. Over the regional scale ~5% of the model SOA is due to the low-NOx aromatic V-SOA pathway, which has a higher yield and produces comparably “low-volatility” species that remain in the particle phase as dilution proceeds and more volatile components evaporate. The model SOA formed from oxidation of both semivolatile and intermediate volatility organic vapors (SI-SOA) accounts for most of the predicted SOA mass concentration. With the SI-SOA parameterization of Robinson et al. (2007) the model matches the observed SOA mass, but its O/C is too low by a factor of 2. With the parameterization of Grieshop et al. (2009) the total SOA mass is overpredicted by a factor of ~2 but O/C and volatility are much closer to the observations. Heating or dilution of the air results in evaporation of a substantial fraction of the model SOA; this fraction is reduced by aging although differently for heating vs. dilution. Finally, lifting of the airmass to the free-troposphere during dry convection results in a substantial increase of SOA by condensation of semivolatile vapors, with this effect being reduced by aging.

  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. Modeling shortwave solar radiation using the JGrass-NewAge system

    NASA Astrophysics Data System (ADS)

    Formetta, G.; Rigon, R.; Chávez, J. L.; David, O.

    2013-07-01

    This paper presents two new modeling components based on the object modeling system v3 (OMS3) for the calculation of the shortwave incident radiation (Rsw↓) on complex topography settings, and the implementation of several ancillary tools. The first component, NewAGE-SwRB, accounts for elevation slope, aspect, shadow of the sites, and uses suitable parameterization for obtaining the cloudless irradiance. A second component, NewAGE-DEC-MOD's is implemented to estimate the irradiance reduction due to the presence of clouds according to three parameterizations. To obtain a working modeling composition that is comparable with ground data at measurement stations the two components are connected to a kriging component. With the help of an additional component, NewAGE-V (verification package), the performance of modeled (Rsw↓) is quantitatively evaluated. The two components (and the various parameterizations they contain) are tested using the data from three basins, and some simple verification tests were carried out to assess the goodness of the methods used. Moreover, a raster mode test is performed in order to show the capability of the system in providing solar radiation raster maps. The components are part of a larger system, JGrass-NewAGE, their input and outputs are geometrical objects immediately displayed in a geographical information system (GIS). They can be used seamlessly with the various modeling solutions available in JGrass-NewAGE for the estimation of long wave radiation, evapotranspiration, and snow melting, as well as standalone components to just estimate shortwave radiation for various uses. The modularity of the approach leads to more accurate physical-statistical studies aimed to assess in depth the components' performances and extends their results spatially, without the necessity of recoding any part of the component.

  10. An alternative Cattell-Horn-Carroll (CHC) factor structure of the WAIS-IV: age invariance of an alternative model for ages 70-90.

    PubMed

    Niileksela, Christopher R; Reynolds, Matthew R; Kaufman, Alan S

    2013-06-01

    The Wechsler Adult Intelligence Scale--Fourth Edition (WAIS-IV) is by the far the most popular intelligence test for the assessment of adults in clinical and neuropsychological practice. Despite a number of studies examining the factor structure of the WAIS-IV from a Cattell-Horn-Carroll (CHC) perspective (Benson, Hulac, & Kranzler, 2010; Ward, Bergman, & Hebert, 2012), a CHC interpretation of the WAIS-IV for individuals ages 70 and above has been absent from the literature. The exclusion of individuals ages 70 and above in previous research is likely due to the absence of several key supplemental subtests used to create a full CHC model. We provide an alternative five-factor CHC model of the WAIS-IV which includes only the subtests administered to individuals ages 70 and above in the standardization sample. Our results show (a) the alternative CHC model fits the data well; (b) this alternative CHC model met criteria for partial strict measurement invariance across the life span (only Similarities showed noninvariance) using strict criteria; (c) the five factors for ages 70-90 measure the same five CHC broad abilities identified in previous analyses reported for ages 16-69; and (d) the five-factor CHC solution for ages 70-90 is valid for the entire WAIS-IV age range and can be used whenever examiners administer the core battery but opt not to administer supplemental subtests. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  11. 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…

  12. 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…

  13. 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

  14. 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

  15. Are invertebrates relevant models in ageing research? Focus on the effects of rapamycin on TOR.

    PubMed

    Erdogan, Cihan Suleyman; Hansen, Benni Winding; Vang, Ole

    2016-01-01

    Ageing is the organisms increased susceptibility to death, which is linked to accumulated damage in the cells and tissues. Ageing is a complex process regulated by crosstalk of various pathways in the cells. Ageing is highly regulated by the Target of Rapamycin (TOR) pathway activity. TOR is an evolutionary conserved key protein kinase in the TOR pathway that regulates growth, proliferation and cell metabolism in response to nutrients, growth factors and stress. Comparing the ageing process in invertebrate model organisms with relatively short lifespan with mammals provides valuable information about the molecular mechanisms underlying the ageing process faster than mammal systems. Inhibition of the TOR pathway activity via either genetic manipulation or rapamycin increases lifespan profoundly in most invertebrate model organisms. This contribution will review the recent findings in invertebrates concerning the TOR pathway and effects of TOR inhibition by rapamycin on lifespan. Besides some contradictory results, the majority points out that rapamycin induces longevity. This suggests that administration of rapamycin in invertebrates is a promising tool for pursuing the scientific puzzle of lifespan prolongation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. 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

  17. Mechanisms of skeletal muscle aging: insights from Drosophila and mammalian models

    PubMed Central

    Demontis, Fabio; Piccirillo, Rosanna; Goldberg, Alfred L.; Perrimon, Norbert

    2013-01-01

    A characteristic feature of aged humans and other mammals is the debilitating, progressive loss of skeletal muscle function and mass that is known as sarcopenia. Age-related muscle dysfunction occurs to an even greater extent during the relatively short lifespan of the fruit fly Drosophila melanogaster. Studies in model organisms indicate that sarcopenia is driven by a combination of muscle tissue extrinsic and intrinsic factors, and that it fundamentally differs from the rapid atrophy of muscles observed following disuse and fasting. Extrinsic changes in innervation, stem cell function and endocrine regulation of muscle homeostasis contribute to muscle aging. In addition, organelle dysfunction and compromised protein homeostasis are among the primary intrinsic causes. Some of these age-related changes can in turn contribute to the induction of compensatory stress responses that have a protective role during muscle aging. In this Review, we outline how studies in Drosophila and mammalian model organisms can each provide distinct advantages to facilitate the understanding of this complex multifactorial condition and how they can be used to identify suitable therapies. PMID:24092876

  18. Mechanisms of skeletal muscle aging: insights from Drosophila and mammalian models.

    PubMed

    Demontis, Fabio; Piccirillo, Rosanna; Goldberg, Alfred L; Perrimon, Norbert

    2013-11-01

    A characteristic feature of aged humans and other mammals is the debilitating, progressive loss of skeletal muscle function and mass that is known as sarcopenia. Age-related muscle dysfunction occurs to an even greater extent during the relatively short lifespan of the fruit fly Drosophila melanogaster. Studies in model organisms indicate that sarcopenia is driven by a combination of muscle tissue extrinsic and intrinsic factors, and that it fundamentally differs from the rapid atrophy of muscles observed following disuse and fasting. Extrinsic changes in innervation, stem cell function and endocrine regulation of muscle homeostasis contribute to muscle aging. In addition, organelle dysfunction and compromised protein homeostasis are among the primary intrinsic causes. Some of these age-related changes can in turn contribute to the induction of compensatory stress responses that have a protective role during muscle aging. In this Review, we outline how studies in Drosophila and mammalian model organisms can each provide distinct advantages to facilitate the understanding of this complex multifactorial condition and how they can be used to identify suitable therapies.

  19. Dietary restriction delays aging, but not neuronal dysfunction, in Drosophila models of Alzheimer's disease

    PubMed Central

    Kerr, F.; Augustin, H.; Piper, M.D.W.; Gandy, C.; Allen, M.J.; Lovestone, S.; Partridge, L.

    2011-01-01

    Dietary restriction (DR) extends lifespan in diverse organisms and, in animal and cellular models, can delay a range of aging-related diseases including Alzheimer's disease (AD). A better understanding of the mechanisms mediating these interactions, however, may reveal novel pathways involved in AD pathogenesis, and potential targets for disease-modifying treatments and biomarkers for disease progression. Drosophila models of AD have recently been developed and, due to their short lifespan and susceptibility to genetic manipulation, we have used the fly to investigate the molecular connections among diet, aging and AD pathology. DR extended lifespan in both Arctic mutant Aβ42 and WT 4R tau over-expressing flies, but the underlying molecular pathology was not altered and neuronal dysfunction was not prevented by dietary manipulation. Our data suggest that DR may alter aging through generalised mechanisms independent of the specific pathways underlying AD pathogenesis in the fly, and hence that lifespan-extending manipulations may have varying effects on aging and functional declines in aging-related diseases. Alternatively, our analysis of the specific effects of DR on neuronal toxicity downstream of Aβ and tau pathologies with negative results may simply confirm that the neuro-protective effects of DR are upstream of the initiating events involved in the pathogenesis of AD. PMID:19969390

  20. 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

    2015-08-28

    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.

  1. 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

  2. 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

    2014-03-13

    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.

  3. 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 tephr