WorldWideScience

Sample records for cell age structure

  1. Chromatin Structure in Cell Differentiation, Aging and Cancer

    NARCIS (Netherlands)

    S. Kheradmand Kia (Sima)

    2009-01-01

    textabstractChromatin is the structure that the eukaryotic genome is packaged into, allowing over a metre of DNA to fit into the small volume of the nucleus. It is composed of DNA and proteins, most of which are histones. This DNA-protein complex is the template for a number of essential cell proces

  2. Immune response in virus model structured by cell infection-age.

    Science.gov (United States)

    Browne, Cameron

    2016-10-01

    This paper concerns modeling the coupled within-host population dynamics of virus and CTL (Cytotoxic T Lymphocyte) immune response. There is substantial evidence that the CTL immune response plays a crucial role in controlling HIV in infected patients. Recent experimental studies have demonstrated that certain CTL variants can recognize HIV infected cells early in the infected cell lifecycle before viral production, while other CTLs only detect viral proteins (epitopes) presented on the surface of infected cells after viral production. The kinetics of epitope presentation and immune recognition can impact the efficacy of the immune response. We extend previous virus models to include cell infection-age structure in the infected cell compartment and immune response killing/activation rates of a PDE-ODE system. We characterize solutions to our system utilizing semigroup theory, determine equilibria and reproduction numbers, and prove stability and persistence results. Numerical simulations show that ' early immune recognition' precipitates both enhanced viral control and sustained oscillations via a Hopf bifurcation. In addition to inducing oscillatory dynamics, considering immune process rates to be functions of cell infection-age can also lead to coexistence of multiple distinct immune effector populations.

  3. Quantitative analysis of mechanisms that govern red blood cell age structure and dynamics during anaemia.

    Directory of Open Access Journals (Sweden)

    Nicholas J Savill

    2009-06-01

    Full Text Available Mathematical modelling has proven an important tool in elucidating and quantifying mechanisms that govern the age structure and population dynamics of red blood cells (RBCs. Here we synthesise ideas from previous experimental data and the mathematical modelling literature with new data in order to test hypotheses and generate new predictions about these mechanisms. The result is a set of competing hypotheses about three intrinsic mechanisms: the feedback from circulating RBC concentration to production rate of immature RBCs (reticulocytes in bone marrow, the release of reticulocytes from bone marrow into the circulation, and their subsequent ageing and clearance. In addition we examine two mechanisms specific to our experimental system: the effect of phenylhydrazine (PHZ and blood sampling on RBC dynamics. We performed a set of experiments to quantify the dynamics of reticulocyte proportion, RBC concentration, and erythropoietin concentration in PHZ-induced anaemic mice. By quantifying experimental error we are able to fit and assess each hypothesis against our data and recover parameter estimates using Markov chain Monte Carlo based Bayesian inference. We find that, under normal conditions, about 3% of reticulocytes are released early from bone marrow and upon maturation all cells are released immediately. In the circulation, RBCs undergo random clearance but have a maximum lifespan of about 50 days. Under anaemic conditions reticulocyte production rate is linearly correlated with the difference between normal and anaemic RBC concentrations, and their release rate is exponentially correlated with the same. PHZ appears to age rather than kill RBCs, and younger RBCs are affected more than older RBCs. Blood sampling caused short aperiodic spikes in the proportion of reticulocytes which appear to have a different developmental pathway than normal reticulocytes. We also provide evidence of large diurnal oscillations in serum erythropoietin levels

  4. NIA Aging Cell Repository

    Data.gov (United States)

    Federal Laboratory Consortium — To facilitate aging research on cells in culture, the NIA provides support for the NIA Aging Cell Repository, located at the Coriell Institute for Medical Research...

  5. A note on the global properties of an age-structured viral dynamic model with multiple target cell populations.

    Science.gov (United States)

    Wang, Shaoli; Wu, Jianhong; Rong, Libin

    2017-06-01

    Some viruses can infect different classes of cells. The age of infection can affect the dynamics of infected cells and viral production. Here we develop a viral dynamic model with the age of infection and multiple target cell populations. Using the methods of semigroup and Lyapunov function, we study the global asymptotic property of the steady states of the model. The results show that when the basic reproductive number falls below 1, the infection is predicted to die out. When the basic reproductive number exceeds 1, there exists a unique infected steady state which is globally asymptotically stable. The model can be extended to study virus dynamics with multiple compartments or coinfection by multiple types of viruses. We also show that under some scenarios the age-structured model can be reduced to an ordinary differential equation system with or without time delays.

  6. Mathematical model of the primary CD8 T cell immune response: stability analysis of a nonlinear age-structured system.

    Science.gov (United States)

    Terry, Emmanuelle; Marvel, Jacqueline; Arpin, Christophe; Gandrillon, Olivier; Crauste, Fabien

    2012-08-01

    The primary CD8 T cell immune response, due to a first encounter with a pathogen, happens in two phases: an expansion phase, with a fast increase of T cell count, followed by a contraction phase. This contraction phase is followed by the generation of memory cells. These latter are specific of the antigen and will allow a faster and stronger response when encountering the antigen for the second time. We propose a nonlinear mathematical model describing the T CD8 immune response to a primary infection, based on three nonlinear ordinary differential equations and one nonlinear age-structured partial differential equation, describing the evolution of CD8 T cell count and pathogen amount. We discuss in particular the roles and relevance of feedback controls that regulate the response. First we reduce our system to a system with a nonlinear differential equation with a distributed delay. We study the existence of two steady states, and we analyze the asymptotic stability of these steady states. Second we study the system with a discrete delay, and analyze global asymptotic stability of steady states. Finally, we show some simulations that we can obtain from the model and confront them to experimental data.

  7. Stem cells and healthy aging.

    Science.gov (United States)

    Goodell, Margaret A; Rando, Thomas A

    2015-12-04

    Research into stem cells and aging aims to understand how stem cells maintain tissue health, what mechanisms ultimately lead to decline in stem cell function with age, and how the regenerative capacity of somatic stem cells can be enhanced to promote healthy aging. Here, we explore the effects of aging on stem cells in different tissues. Recent research has focused on the ways that genetic mutations, epigenetic changes, and the extrinsic environmental milieu influence stem cell functionality over time. We describe each of these three factors, the ways in which they interact, and how these interactions decrease stem cell health over time. We are optimistic that a better understanding of these changes will uncover potential strategies to enhance stem cell function and increase tissue resiliency into old age.

  8. Structural aging program status report

    Energy Technology Data Exchange (ETDEWEB)

    Naus, D.J.; Oland, C.B. [Oak Ridge National Lab., TN (United States); Ellingwood, B. [Johns Hopkins Univ., Baltimore, MD (United States)] [and others

    1995-04-01

    Research is being conducted at the Oak Ridge National Laboratory (ORNL) under U.S. Nuclear Regulatory Commission (USNRC) sponsorship to address aging management of safety-related concrete structures. Documentation is being prepared to provide the USNRC with potential structural safety issues and acceptance criteria for use in continued service evaluations of nuclear power plants. Program accomplishments have included development of the Structural Materials Information Center containing data and information of the time variation of 144 material properties under the influence of pertinent environmental stressors of aging factors, performance assessments of reinforced concrete structures in several United Kingdom nuclear power facilities, evaluation of European and North American repair practices for concrete, an evaluation of factors affecting the corrosion of metals embedded in concrete, and application of the time-dependent reliability methodology to reinforced concrete flexure and shear structural elements to investigate the role of in-service inspection and repair on their probability of failure.

  9. The cell biology of aging

    Science.gov (United States)

    DiLoreto, Race; Murphy, Coleen T.

    2015-01-01

    One of the original hypotheses of organismal longevity posits that aging is the natural result of entropy on the cells, tissues, and organs of the animal—a slow, inexorable slide into nonfunctionality caused by stochastic degradation of its parts. We now have evidence that aging is instead at least in part genetically regulated. Many mutations have been discovered to extend lifespan in organisms of all complexities, from yeast to mammals. The study of metazoan model organisms, such as Caenorhabditis elegans, has been instrumental in understanding the role of genetics in the cell biology of aging. Longevity mutants across the spectrum of model organisms demonstrate that rates of aging are regulated through genetic control of cellular processes. The regulation and subsequent breakdown of cellular processes represent a programmatic decision by the cell to either continue or abandon maintenance procedures with age. Our understanding of cell biological processes involved in regulating aging have been particularly informed by longevity mutants and treatments, such as reduced insulin/IGF-1 signaling and dietary restriction, which are critical in determining the distinction between causes of and responses to aging and have revealed a set of downstream targets that participate in a range of cell biological activities. Here we briefly review some of these important cellular processes. PMID:26668170

  10. Stem cell mitochondria during aging.

    Science.gov (United States)

    Min-Wen, Jason Chua; Jun-Hao, Elwin Tan; Shyh-Chang, Ng

    2016-04-01

    Mitochondria are the central hubs of cellular metabolism, equipped with their own mitochondrial DNA (mtDNA) blueprints to direct part of the programming of mitochondrial oxidative metabolism and thus reactive oxygen species (ROS) levels. In stem cells, many stem cell factors governing the intricate balance between self-renewal and differentiation have been found to directly regulate mitochondrial processes to control stem cell behaviors during tissue regeneration and aging. Moreover, numerous nutrient-sensitive signaling pathways controlling organismal longevity in an evolutionarily conserved fashion also influence stem cell-mediated tissue homeostasis during aging via regulation of stem cell mitochondria. At the genomic level, it has been demonstrated that heritable mtDNA mutations and variants affect mammalian stem cell homeostasis and influence the risk for human degenerative diseases during aging. Because such a multitude of stem cell factors and signaling pathways ultimately converge on the mitochondria as the primary mechanism to modulate cellular and organismal longevity, it would be most efficacious to develop technologies to therapeutically target and direct mitochondrial repair in stem cells, as a unified strategy to combat aging-related degenerative diseases in the future.

  11. Normal and aging hair biology and structure 'aging and hair'.

    Science.gov (United States)

    Goodier, Molly; Hordinsky, Maria

    2015-01-01

    Much like an individual's hairstyle, hair fibers along the scalp see a number of changes over the course of one's lifetime. As the decades pass, the shine and volume synonymous with youthful hair may give way to thin, dull, and brittle hair commonly associated with aging. These changes are a result of a compilation of genetic and environmental elements influencing the cells of the hair follicle, specifically the hair follicle stem cells and melanocytes. Telomere shortening, decrease in cell numbers, and particular transcription factors have all been implicated in this process. In turn, these molecular alterations lead to structural modifications of the hair fiber, decrease in melanin production, and lengthening of the telogen phase of the hair cycle. Despite this inevitable progression with aging, there exists an array of treatments such as light therapy, minoxidil, and finasteride which have been designed to mitigate the effects of aging, particularly balding and thinning hair. Although each works through a different mechanism, all aim to maintain or potentially restore the youthful quality of hair.

  12. Klotho, stem cells, and aging.

    Science.gov (United States)

    Bian, Ao; Neyra, Javier A; Zhan, Ming; Hu, Ming Chang

    2015-01-01

    Aging is an inevitable and progressive biological process involving dysfunction and eventually destruction of every tissue and organ. This process is driven by a tightly regulated and complex interplay between genetic and acquired factors. Klotho is an antiaging gene encoding a single-pass transmembrane protein, klotho, which serves as an aging suppressor through a wide variety of mechanisms, such as antioxidation, antisenescence, antiautophagy, and modulation of many signaling pathways, including insulin-like growth factor and Wnt. Klotho deficiency activates Wnt expression and activity contributing to senescence and depletion of stem cells, which consequently triggers tissue atrophy and fibrosis. In contrast, the klotho protein was shown to suppress Wnt-signaling transduction, and inhibit cell senescence and preserve stem cells. A better understanding of the potential effects of klotho on stem cells could offer novel insights into the cellular and molecular mechanisms of klotho deficiency-related aging and disease. The klotho protein may be a promising therapeutic agent for aging and aging-related disorders.

  13. A cell adhesion molecule mimetic, FGL peptide, induces alterations in synapse and dendritic spine structure in the dentate gyrus of aged rats: a three-dimensional ultrastructural study

    DEFF Research Database (Denmark)

    Popov, Victor I; Medvedev, Nikolay I; Kraev, Igor V

    2008-01-01

    The FGL peptide is a neural cell adhesion molecule (NCAM) mimetic comprising a 15-amino-acid-long sequence of the FG loop region of the second fibronectin type III module of NCAM. It corresponds to the binding site of NCAM for the fibroblast growth factor receptor 1. FGL improves cognitive function...... through enhancement of synaptic function. We examined the effect of FGL on synaptic and dendritic structure in the brains of aged (22-month-old) rats that were injected subcutaneously (8 mg/kg) at 2-day intervals until 19 days after the start of the experiment. Animals were perfused with fixative, brains...... removed and coronal sections cut at 50 microm. The hippocampal volume was measured, tissue embedded and ultrathin sections viewed in a JEOL 1010 electron microscope. Analyses were made of synaptic and dendritic parameters following three-dimensional reconstruction via images from a series of approximately...

  14. An age-structured population balance model for microbial dynamics

    Directory of Open Access Journals (Sweden)

    Duarte M.V.E.

    2003-01-01

    Full Text Available This work presents an age-structured population balance model (ASPBM for a bioprocess in a continuous stirred-tank fermentor. It relates the macroscopic properties and dynamic behavior of biomass to the operational parameters and microscopic properties of cells. Population dynamics is governed by two time- and age-dependent density functions for living and dead cells, accounting for the influence of substrate and dissolved oxygen concentrations on cell division, aging and death processes. The ASPBM described biomass and substrate oscillations in aerobic continuous cultures as experimentally observed. It is noteworthy that a small data set consisting of nonsegregated measurements was sufficient to adjust a complex segregated mathematical model.

  15. Thermodynamic concepts in the study of microbial populations: age structure in Plasmodium falciparum infected red blood cells.

    Directory of Open Access Journals (Sweden)

    Jordi Ferrer

    Full Text Available Variability is a hallmark of microbial systems. On the one hand, microbes are subject to environmental heterogeneity and undergo changeable conditions in their immediate surroundings. On the other hand, microbial populations exhibit high cellular diversity. The relation between microbial diversity and variability of population dynamics is difficult to assess. This connection can be quantitatively studied from a perspective that combines in silico models and thermodynamic methods and interpretations. The infection process of Plasmodium falciparum parasitizing human red blood cells under laboratory cultivation conditions is used to illustrate the potential of Individual-based models in the context of predictive microbiology and parasitology. Experimental data from several in vitro cultures are compared to the outcome of an individual-based model and analysed from a thermodynamic perspective. This approach allows distinguishing between intrinsic and external constraints that give rise to the diversity in the infection forms, and it provides a criterion to quantitatively define transient and stationary regimes in the culture. Increasing the ability of models to discriminate between different states of microbial populations enhances their predictive capability which finally leads to a better the control over culture systems. The strategy here presented is of general application and it can substantially improve modelling of other types of microbial communities.

  16. Thermodynamic concepts in the study of microbial populations: age structure in Plasmodium falciparum infected red blood cells.

    Science.gov (United States)

    Ferrer, Jordi; Prats, Clara; López, Daniel; Vidal-Mas, Jaume; Gargallo-Viola, Domingo; Guglietta, Antonio; Giró, Antoni

    2011-01-01

    Variability is a hallmark of microbial systems. On the one hand, microbes are subject to environmental heterogeneity and undergo changeable conditions in their immediate surroundings. On the other hand, microbial populations exhibit high cellular diversity. The relation between microbial diversity and variability of population dynamics is difficult to assess. This connection can be quantitatively studied from a perspective that combines in silico models and thermodynamic methods and interpretations. The infection process of Plasmodium falciparum parasitizing human red blood cells under laboratory cultivation conditions is used to illustrate the potential of Individual-based models in the context of predictive microbiology and parasitology. Experimental data from several in vitro cultures are compared to the outcome of an individual-based model and analysed from a thermodynamic perspective. This approach allows distinguishing between intrinsic and external constraints that give rise to the diversity in the infection forms, and it provides a criterion to quantitatively define transient and stationary regimes in the culture. Increasing the ability of models to discriminate between different states of microbial populations enhances their predictive capability which finally leads to a better the control over culture systems. The strategy here presented is of general application and it can substantially improve modelling of other types of microbial communities.

  17. Effect of aging on stem cells

    Science.gov (United States)

    Ahmed, Abu Shufian Ishtiaq; Sheng, Matilda HC; Wasnik, Samiksha; Baylink, David J; Lau, Kin-Hing William

    2017-01-01

    Pluripotent stem cells have the remarkable self-renewal ability and are capable of differentiating into multiple diverse cells. There is increasing evidence that the aging process can have adverse effects on stem cells. As stem cells age, their renewal ability deteriorates and their ability to differentiate into the various cell types is altered. Accordingly, it is suggested aging-induced deterioration of stem cell functions may play a key role in the pathophysiology of the various aging-associated disorders. Understanding the role of the aging process in deterioration of stem cell function is crucial, not only in understanding the pathophysiology of aging-associated disorders, but also in future development of novel effective stem cell-based therapies to treat aging-associated diseases. This review article first focuses on the basis of the various aging disease-related stem cell dysfunction. It then addresses the several concepts on the potential mechanism that causes aging-related stem cell dysfunction. It also briefly discusses the current potential therapies under development for aging-associated stem cell defects.

  18. Aging and senescence of skin cells in culture

    DEFF Research Database (Denmark)

    Rattan, Suresh

    2015-01-01

    aging in vitro are dermal fibroblasts, epidermal keratinocytes, and melanocytes. Serial subcultivation of normal diploid skin cells can be performed only a limited number of times, and the emerging senescent phenotype can be categorized into structural, physiological, biochemical, and molecular......Studying age-related changes in the physiology, biochemistry, and molecular biology of isolated skin cell populations in culture has greatly expanded the understanding of the fundamental aspects of skin aging. The three main cell types that have been studied extensively with respect to cellular...... phenotypes, which can be used as biomarkers of cellular aging in vitro. The rate and phenotype of aging are different in different cell types. There are both common features and specific features of aging of skin fibroblasts, keratinocytes, melanocytes, and other cell types. A progressive accumulation...

  19. The Stem Cell Hypothesis of Aging

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2010-04-01

    Full Text Available BACKGROUND: There is probably no single way to age. Indeed, so far there is no single accepted explanation or mechanisms of aging (although more than 300 theories have been proposed. There is an overall decline in tissue regenerative potential with age, and the question arises as to whether this is due to the intrinsic aging of stem cells or rather to the impairment of stem cell function in the aged tissue environment. CONTENT: Recent data suggest that we age, in part, because our self-renewing stem cells grow old as a result of heritable intrinsic events, such as DNA damage, as well as extrinsic forces, such as changes in their supporting niches. Mechanisms that suppress the development of cancer, such as senescence and apoptosis, which rely on telomere shortening and the activities of p53 and p16INK4a may also induce an unwanted consequence: a decline in the replicative function of certain stem cells types with advancing age. This decrease regenerative capacity appears to pointing to the stem cell hypothesis of aging. SUMMARY: Recent evidence suggested that we grow old partly because of our stem cells grow old as a result of mechanisms that suppress the development of cancer over a lifetime. We believe that a further, more precise mechanistic understanding of this process will be required before this knowledge can be translated into human anti-aging therapies. KEYWORDS: stem cells, senescence, telomere, DNA damage, epigenetic, aging.

  20. Centrosome and microtubule instability in aging Drosophila cells

    Science.gov (United States)

    Schatten, H.; Chakrabarti, A.; Hedrick, J.

    1999-01-01

    Several cytoskeletal changes are associated with aging which includes alterations in muscle structure leading to muscular atrophy, and weakening of the microtubule network which affects cellular secretion and maintenance of cell shape. Weakening of the microtubule network during meiosis in aging oocytes can result in aneuploidy or trisomic zygotes with increasing maternal age. Imbalances of cytoskeletal organization can lead to disease such as Alzheimer's, muscular disorders, and cancer. Because many cytoskeletal diseases are related to age we investigated the effects of aging on microtubule organization in cell cultures of the Drosophila cell model system (Schneider S-1 and Kc23 cell lines). This cell model is increasingly being used as an alternative system to mammalian cell cultures. Drosophila cells are amenable to genetic manipulations and can be used to identify and manipulate genes which are involved in the aging processes. Immunofluorescence, scanning, and transmission electron microscopy were employed for the analysis of microtubule organizing centers (centrosomes) and microtubules at various times after subculturing cells in fresh medium. Our results reveal that centrosomes and the microtubule network becomes significantly affected in aging cells after 5 days of subculture. At 5-14 days of subculture, 1% abnormal out of 3% mitoses were noted which were clearly distinguishable from freshly subcultured control cells in which 3% of cells undergo normal mitosis with bipolar configurations. Microtubules are also affected in the midbody during cell division. The midbody in aging cells becomes up to 10 times longer when compared with midbodies in freshly subcultured cells. During interphase, microtubules are often disrupted and disorganized, which may indicate improper function related to transport of cell organelles along microtubules. These results are likely to help explain some cytoskeletal disorders and diseases related to aging.

  1. Structural imaging measures of brain aging.

    Science.gov (United States)

    Lockhart, Samuel N; DeCarli, Charles

    2014-09-01

    During the course of normal aging, biological changes occur in the brain that are associated with changes in cognitive ability. This review presents data from neuroimaging studies of primarily "normal" or healthy brain aging. As such, we focus on research in unimpaired or nondemented older adults, but also include findings from lifespan studies that include younger and middle aged individuals as well as from populations with prodromal or clinically symptomatic disease such as cerebrovascular or Alzheimer's disease. This review predominantly addresses structural MRI biomarkers, such as volumetric or thickness measures from anatomical images, and measures of white matter injury and integrity respectively from FLAIR or DTI, and includes complementary data from PET and cognitive or clinical testing as appropriate. The findings reveal highly consistent age-related differences in brain structure, particularly frontal lobe and medial temporal regions that are also accompanied by age-related differences in frontal and medial temporal lobe mediated cognitive abilities. Newer findings also suggest that degeneration of specific white matter tracts such as those passing through the genu and splenium of the corpus callosum may also be related to age-related differences in cognitive performance. Interpretation of these findings, however, must be tempered by the fact that comorbid diseases such as cerebrovascular and Alzheimer's disease also increase in prevalence with advancing age. As such, this review discusses challenges related to interpretation of current theories of cognitive aging in light of the common occurrence of these later-life diseases. Understanding the differences between "Normal" and "Healthy" brain aging and identifying potential modifiable risk factors for brain aging is critical to inform potential treatments to stall or reverse the effects of brain aging and possibly extend cognitive health for our aging society.

  2. Stem cells and the aging hematopoietic system.

    Science.gov (United States)

    Beerman, Isabel; Maloney, William J; Weissmann, Irving L; Rossi, Derrick J

    2010-08-01

    Advancing age is accompanied by a number of clinically significant conditions arising in the hematopoietic system that include: diminution and decreased competence of the adaptive immune system, elevated incidence of certain autoimmune diseases, increased hematological malignancies, and elevated incidence of age-associated anemia. As with most tissues, the aged hematopoietic system also exhibits a reduced capacity to regenerate and return to normal homeostasis after injury or stress. Evidence suggests age-dependent functional alterations within the hematopoietic stem cell compartment significantly contribute to many of these pathophysiologies. Recent developments have shed light on how aging of the hematopoietic stem cell compartment contributes to hematopoietic decline through diverse mechanisms.

  3. In Search for Anti-Aging Strategy: Can We Rejuvenate Our Aging Stem Cells?

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2015-08-01

    Full Text Available BACKGROUND: Recent evidence suggested that we grow old partly because of our stem cells grow old as a result of mechanisms that suppress the development of cancer over a lifetime. We believe that a further, more precise mechanistic understanding of this process will be required before this knowledge can be translated into human anti-aging therapies. CONTENT: A diminished capacity to maintain tissue homeostasis is a central physiological characteristic of aging. As stem cells regulate tissue homeostasis, depletion of stem cell reserves and/or diminished stem cell function have been postulated to contribute to aging. It has further been suggested that accumulated DNA damage could be a principal mechanism underlying age-dependent stem cell decline. It is interesting that many of the rejuvenating interventions act on the stem cell compartments, perhaps reflecting shared genetic and biochemical pathways controlling stem cell function and longevity. Strategy to slow down the aging processes is based on caloric restriction refers to a dietary regimen low in calories but without undernutrition. Sirtuin (SIRT1 and 3, increases longevity by mimicking the beneficial effects of caloric restriction. SIRT3 regulates stress-responsive mitochondrial homeostasis, and more importantly, SIRT3 upregulation rejuvenates aged stem cells in tissues. Resveratrol (3,5,4’-trihydroxystilbene, a natural polyphenol found in grapes and wine, was the most powerful natural activator of SIRT1. In fact, resveratrol treatment has been demonstrated to rescue adult stem cell decline, slow down bodyweight loss, improve trabecular bone structure and mineral density, and significantly extend lifespan. SUMMARY: Tissue-specific stem cells persist throughout the entire lifespan to repair and maintain tissues, but their self-renewal and differentiation potential become dysregulated with aging. Given that adult stem cells are thought to be central to tissue maintenance and organismal

  4. Adult Stem Cells and Diseases of Aging

    Directory of Open Access Journals (Sweden)

    Lisa B. Boyette

    2014-01-01

    Full Text Available Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan.

  5. Stem cell aging in adult progeria.

    Science.gov (United States)

    Cheung, Hoi-Hung; Pei, Duanqing; Chan, Wai-Yee

    2015-01-01

    Aging is considered an irreversible biological process and also a major risk factor for a spectrum of geriatric diseases. Advanced age-related decline in physiological functions, such as neurodegeneration, development of cardiovascular disease, endocrine and metabolic dysfunction, and neoplastic transformation, has become the focus in aging research. Natural aging is not regarded as a programmed process. However, accelerated aging due to inherited genetic defects in patients of progeria is programmed and resembles many aspects of natural aging. Among several premature aging syndromes, Werner syndrome (WS) and Hutchinson-Gilford progeria syndrome (HGPS) are two broadly investigated diseases. In this review, we discuss how stem cell aging in WS helps us understand the biology of aging. We also discuss briefly how the altered epigenetic landscape in aged cells can be reversed to a "juvenile" state. Lastly, we explore the potential application of the latest genomic editing technique for stem cell-based therapy and regenerative medicine in the context of aging.

  6. Structural Neuroimaging in Aging and Alzheimer's Disease

    NARCIS (Netherlands)

    Vernooij, Meike W.; Smits, Marion

    2012-01-01

    The role of structural neuroimaging in the diagnosis of Alzheimer's disease (AD) is becoming increasingly important. As a consequence, a basic understanding of what are normal brain changes in aging is key to be able to recognize what is abnormal. The first part of this article discusses normal vers

  7. [Age-related characteristics of structural support for ovarian function].

    Science.gov (United States)

    Koval'skiĭ, G B

    1984-12-01

    Histoenzymological assay was used to investigate various structures of the ovaries of rats of two groups aged 3-4 and 12-14 months during estral cycle. The activity of 3 beta-, 17 beta- and 20 alpha-steroid dehydrogenases, glucose-6-phosphate dehydrogenase, NAD and NADP-diaphorases, esterase, acid and alkaline phosphatases was studied. It has been shown that transport alterations in the microcirculation including the hematofollicular barrier play, the leading part in age-dependent depression of reproductive and endocrine functions. Ageing rats demonstrated no linkage between endothelial, thecal and granular cells, which points to the injury of the histophysiological mechanisms of the follicular system integration.

  8. Ageing and cell-mediated immunity.

    Science.gov (United States)

    Fixa, B; Komárková, O; Chmelar, V

    1975-01-01

    The lymphocyte transformation test with phytohemagglutinin as mitogen estimated according to the incorporation of 2-(14)C-thymidine in DNA was used as an indicator of cell-mediated reactivity in 53 healthy subjects. Three age groups were examined: up to 20 years (21 subjects), 21-40 years (10 subjects) and over 70 years (22 subjects). The responsiveness of lymphocytes decreased significantly with age. In the highest age group 12 pathologically low values were found.

  9. Ageing in civil engineering materials and structures

    Energy Technology Data Exchange (ETDEWEB)

    Jaeger, Jean-Marc [SETEC TPI, Tour Gamma D 58, quai de la Rapee, 75583 Paris (France)

    2005-07-01

    SETEC TPI will address the 'Aging' topic of the Dijon Symposium by talking about: aging in civil engineering materials and structures, prevention of aging phenomena, in-operation monitoring of degradations related to aging and compensatory measures required to maintain a good safety level. Works as the Millau viaduct, the EdF skyscraper at La Defense - Paris, the renovation of the Grand Palais of Paris and special structures with Monaco's floating dam as well as the 'number 10' shaped gateway boat at Marseilles are illustrations for the issues discussed. The durability of civil engineering structures has become a major concern for designers. The Millau viaduct is designed for a service life of 120 years, and the Monaco dam for 100 years. Calculation rules have been evolving toward the incorporation of the concept of life cycle, for example, the Eurocodes 2 rules (reinforced concrete). The talk will expose the factors which are being taken into account to delay aging versus structure types. This part will be focused towards materials and corresponding regulations: - Reinforced concrete (coating of reinforcements, opening of cracks, choice of reinforcement types), BAEL and Eurocodes 2 rules; - Frame steel (protection, sacrificial anode), CM66 and Eurocodes 3 rules. New materials will also be mentioned: - Ultra high-performance fiber/concrete, with the example of CERACEM applied at Millau for the covering of the toll area barrier; - Titanium, which is starting to appear in the building trades, as for instance for the Beijing China Opera House shell. The second part of the talk will be devoted to a specific case namely, the 'number 10' shaped gateway bridge, a prestressed concrete structure immersed in the Port of Marseilles, which will be used to illustrate the aging phenomenon in a corrosive environment. We will focus on the types of inspection series performed by the Autonomous Port Authority of Marseilles to check the behavior of

  10. Morphological changes in nerve cells during normal aging.

    Science.gov (United States)

    Pannese, Ennio

    2011-06-01

    During normal aging, widespread loss of nerve cells does not occur. Neuronal loss is limited to restricted regions of the nervous system and is slight (probably no more than 10%). The commonest age-related structural changes undergone by nerve cells are as follows: dendrites decrease in number and length and many dendritic spines are lost; axons decrease in number and their myelin sheaths may become less compact and undergo segmental demyelination followed by remyelination; and significant loss of synapses occurs. These changes probably make a significant contribution to the behavioral impairment and cognitive decline that often accompany normal aging.

  11. Epigenetic regulation of hematopoietic stem cell aging

    Energy Technology Data Exchange (ETDEWEB)

    Beerman, Isabel, E-mail: isabel.beerman@childrens.harvard.edu [Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138 (United States); Department of Pediatrics, Harvard Medical School, Boston, MA 02115 (United States); Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children' s Hospital, MA 02116 (United States); Rossi, Derrick J. [Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138 (United States); Department of Pediatrics, Harvard Medical School, Boston, MA 02115 (United States); Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children' s Hospital, MA 02116 (United States)

    2014-12-10

    Aging is invariably associated with alterations of the hematopoietic stem cell (HSC) compartment, including loss of functional capacity, altered clonal composition, and changes in lineage contribution. Although accumulation of DNA damage occurs during HSC aging, it is unlikely such consistent aging phenotypes could be solely attributed to changes in DNA integrity. Another mechanism by which heritable traits could contribute to the changes in the functional potential of aged HSCs is through alterations in the epigenetic landscape of adult stem cells. Indeed, recent studies on hematopoietic stem cells have suggested that altered epigenetic profiles are associated with HSC aging and play a key role in modulating the functional potential of HSCs at different stages during ontogeny. Even small changes of the epigenetic landscape can lead to robustly altered expression patterns, either directly by loss of regulatory control or through indirect, additive effects, ultimately leading to transcriptional changes of the stem cells. Potential drivers of such changes in the epigenetic landscape of aged HSCs include proliferative history, DNA damage, and deregulation of key epigenetic enzymes and complexes. This review will focus largely on the two most characterized epigenetic marks – DNA methylation and histone modifications – but will also discuss the potential role of non-coding RNAs in regulating HSC function during aging.

  12. An age structured demographic model of technology

    CERN Document Server

    Mercure, J -F

    2013-01-01

    At the heart of technology transitions lie complex processes of technology choices. Understanding and planning sustainability transitions requires modelling work, which necessitates a theory of technology substitution. A theoretical model of technological change and turnover is presented, intended as a methodological paradigm shift from widely used conventional modelling approaches such as cost optimisation. It follows the tradition of evolutionary economics and evolutionary game theory, using ecological population growth dynamics to represent the evolution of technology populations in the marketplace, with substitutions taking place at the level of the decision-maker. Extended to use principles of human demography or the age structured evolution of species in interacting ecosystems, this theory is built from first principles, and through an appropriate approximation, reduces to a form identical to empirical models of technology diffusion common in the technology transitions literature. Using an age structure...

  13. Risk Based Inspection Planning of Ageing Structures

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Ersdal, Gerhard

    2008-01-01

    collapse of the structure. The importance of each component can be measured by the RIF (Residual Influence Factor) for each component and is illustrated by examples. When an installation becomes older then the number of fatigue critical components can be expected to increase. If the maximum acceptable....... Different approaches for updating inspection plans for older installations are considered in order to achieve decreased inspection intervals as the structure are ageing. The most promising method consists in increasing the rate of defects / crack initiation at the end of the expected lifetime. Different...

  14. Poststroke Cell Therapy of the Aged Brain

    Directory of Open Access Journals (Sweden)

    Aurel Popa-Wagner

    2015-01-01

    Full Text Available During aging, many neurodegenerative disorders are associated with reduced neurogenesis and a decline in the proliferation of stem/progenitor cells. The development of the stem cell (SC, the regenerative therapy field, gained tremendous expectations in the diseases that suffer from the lack of treatment options. Stem cell based therapy is a promising approach to promote neuroregeneration after brain injury and can be potentiated when combined with supportive pharmacological drug treatment, especially in the aged. However, the mechanism of action for a particular grafted cell type, the optimal delivery route, doses, or time window of administration after lesion is still under debate. Today, it is proved that these protections are most likely due to modulatory mechanisms rather than the expected cell replacement. Our group proved that important differences appear in the aged brain compared with young one, that is, the accelerated progression of ischemic area, or the delayed initiation of neurological recovery. In this light, these age-related aspects should be carefully evaluated in the clinical translation of neurorestorative therapies. This review is focused on the current perspectives and suitable sources of stem cells (SCs, mechanisms of action, and the most efficient delivery routes in neurorestoration therapies in the poststroke aged environment.

  15. Expression of progerin in aging mouse brains reveals structural nuclear abnormalities without detectible significant alterations in gene expression, hippocampal stem cells or behavior

    DEFF Research Database (Denmark)

    Baek, Jean-Ha; Schmidt, Eva; Viceconte, Nikenza;

    2015-01-01

    Hutchinson–Gilford progeria syndrome (HGPS) is a segmental progeroid syndrome with multiple features suggestive of premature accelerated aging. Accumulation of progerin is thought to underlie the pathophysiology of HGPS. However, despite ubiquitous expression of lamin A in all differentiated cells......, the HGPS mutation results in organ-specific defects. For example, bone and skin are strongly affected by HGPS, while the brain appears to be unaffected. There are no definite explanations as to the variable sensitivity to progeria disease among different organs. In addition, low levels of progerin have...

  16. Lysosomal cell death mechanisms in aging.

    Science.gov (United States)

    Gómez-Sintes, Raquel; Ledesma, María Dolores; Boya, Patricia

    2016-12-01

    Lysosomes are degradative organelles essential for cell homeostasis that regulate a variety of processes, from calcium signaling and nutrient responses to autophagic degradation of intracellular components. Lysosomal cell death is mediated by the lethal effects of cathepsins, which are released into the cytoplasm following lysosomal damage. This process of lysosomal membrane permeabilization and cathepsin release is observed in several physiopathological conditions and plays a role in tissue remodeling, the immune response to intracellular pathogens and neurodegenerative diseases. Many evidences indicate that aging strongly influences lysosomal activity by altering the physical and chemical properties of these organelles, rendering them more sensitive to stress. In this review we focus on how aging alters lysosomal function and increases cell sensitivity to lysosomal membrane permeabilization and lysosomal cell death, both in physiological conditions and age-related pathologies.

  17. Cell packing structures

    KAUST Repository

    Pottmann, Helmut

    2015-03-03

    This paper is an overview of architectural structures which are either composed of polyhedral cells or closely related to them. We introduce the concept of a support structure of such a polyhedral cell packing. It is formed by planar quads and obtained by connecting corresponding vertices in two combinatorially equivalent meshes whose corresponding edges are coplanar and thus determine planar quads. Since corresponding triangle meshes only yield trivial structures, we focus on support structures associated with quad meshes or hex-dominant meshes. For the quadrilateral case, we provide a short survey of recent research which reveals beautiful relations to discrete differential geometry. Those are essential for successfully initializing numerical optimization schemes for the computation of quad-based support structures. Hex-dominant structures may be designed via Voronoi tessellations, power diagrams, sphere packings and various extensions of these concepts. Apart from the obvious application as load-bearing structures, we illustrate here a new application to shading and indirect lighting. On a higher level, our work emphasizes the interplay between geometry, optimization, statics, and manufacturing, with the overall aim of combining form, function and fabrication into novel integrated design tools.

  18. [Age changes of the connective tissue structures of human penis].

    Science.gov (United States)

    Klimachev, V V; Neĭmark, A I; Gerval'd, V Ia; Bobrov, I P; Avdalian, A M; Muzalevskaia, N I; Gerval'd, I V; Aliev, R T; Cherdantseva, T M

    2011-01-01

    This investigation was aimed at the study of age changes of penis connective tissue structures. Tissue fragments of penis were obtained from 20 cadavers of men at the age of 20-38 years in group I, and from 20 cadavers of men at the age of 41-59 years in group II. The criteria for the exclusion of material from the research were arterial hypertension, diabetes mellitus, atherosclerosis of internal iliac arteries, Peyronie's disease, and anomalies of genital organ development. It was shown that in the cavernous body of penis, aging was associated with the increased amount and thickening of collagen and argyrophilic fibers, decreased content and thinning of elastic fibers, and the reduced amount of smooth muscle cells (SMC). The average area of fibroblast and SMC nucleolus was not different in both groups studied. The average area of endotheliocyte nucleolus was equal to 1.9+/-0.9 microm2 in group II, being lower than that one in group I, in which this index was equal to 2.1+/-0.9 microm2. No differences in the content of type III and IV collagen were found between the study groups. Age-associated decrease in the average area of endothelial cell nucleolus in the cavernous bodies may reflect the reduction of the activity of these cells and may indicate the development of endothelial dysfunction, which is one of the most important steps in the morphogenesis of age-related male erectile dysfunction.

  19. Endothelial Progenitor Cells Enter the Aging Arena.

    Directory of Open Access Journals (Sweden)

    Kate eWilliamson

    2012-02-01

    Full Text Available Age is a significant risk factor for the development of vascular diseases, such as atherosclerosis. Although pharmacological treatments, including statins and anti-hypertensive drugs, have improved the prognosis for patients with cardiovascular disease, it remains a leading cause of mortality in those aged 65 years and over. Furthermore, given the increased life expectancy of the population in developed countries, there is a clear need for alternative treatment strategies. Consequently, the relationship between aging and progenitor cell-mediated repair is of great interest. Endothelial progenitor cells (EPCs play an integral role in the cellular repair mechanisms for endothelial regeneration and maintenance. However, EPCs are subject to age-associated changes that diminish their number in circulation and function, thereby enhancing vascular disease risk. A great deal of research is aimed at developing strategies to harness the regenerative capacity of these cells.In this review, we discuss the current understanding of the cells termed ‘EPCs’, examine the impact of age on EPC-mediated repair and identify therapeutic targets with potential for attenuating the age-related decline in vascular health via beneficial actions on EPCs.

  20. Intrinsically photosensitive retinal ganglion cell function in relation to age

    DEFF Research Database (Denmark)

    Herbst, Kristina; Sander, Birgit; Lund-Andersen, Henrik;

    2012-01-01

    The activity of melanopsin containing intrinsically photosensitive ganglion retinal cells (ipRGC) can be assessed by a means of pupil responses to bright blue (appr.480 nm) light. Due to age related factors in the eye, particularly, structural changes of the lens, less light reaches retina. The aim...

  1. Anabaena cell ageing monitored with confocal fluorescence spectroscopy.

    Science.gov (United States)

    Ke, Shan; Bindokas, Vytas; Haselkorn, Robert

    2015-01-01

    Cyanobacteria use a sophisticated system of pigments to collect light energy across the visible spectrum for photosynthesis. The pigments are assembled in structures called phycobilisomes, composed of phycoerythrocyanin, phycocyanin and allophycocyanin, which absorb energy and transfer it to chlorophyll in photosystem II reaction centres. All of the components of this system are fluorescent, allowing sensitive measurements of energy transfer using single cell confocal fluorescence microscopy. The native pigments can be interrogated without the use of reporters. Here, we use confocal fluorescence microscopy to monitor changes in the efficiency of energy transfer as single cells age, between the time they are born at cell division until they are ready to divide again. Alteration of fluorescence was demonstrated to change with the age of the cyanobacterial cell.

  2. Erythrocyte aging in sickle cell disease.

    NARCIS (Netherlands)

    Bosman, G.J.C.G.M.

    2004-01-01

    Physiological removal of old erythrocytes from the circulation by macrophages is initiated by binding of autologous IgG to senescent cell antigen (SCA). SCA is generated from the anion exchanger band 3. This process is accompanied by a number of alterations in the function and structure of band 3. W

  3. Estimating population age structure using otolith morphometrics

    DEFF Research Database (Denmark)

    Doering-Arjes, P.; Cardinale, M.; Mosegaard, Henrik

    2008-01-01

    known-age fish individuals. Here we used known-age Atlantic cod (Gadus morhua) from the Faroe Bank and Faroe Plateau stocks. Cod populations usually show quite large variation in growth rates and otolith shape. We showed that including otolith morphometrics into ageing processes has the potential...... to make ageing objective, accurate, and fast. Calibration analysis indicated that a known-age sample from the same population and environment is needed to obtain robust calibration; using a sample from a different stock more than doubles the error rate, even in the case of genetically highly related...... populations. The intercalibration method was successful but generalization from one stock to another remains problematic. The development of an otolith growth model is needed for generalization if an operational method for different populations is required in the future....

  4. Impact of genomic damage and ageing on stem cell function

    NARCIS (Netherlands)

    Behrens, A.; Deursen, J.M. van; Rudolph, K.L.; Schumacher, B.

    2014-01-01

    Impairment of stem cell function contributes to the progressive deterioration of tissue maintenance and repair with ageing. Evidence is mounting that age-dependent accumulation of DNA damage in both stem cells and cells that comprise the stem cell microenvironment are partly responsible for stem cel

  5. Adaptation of brain functional and structural networks in aging.

    Science.gov (United States)

    Lee, Annie; Ratnarajah, Nagulan; Tuan, Ta Anh; Chen, Shen-Hsing Annabel; Qiu, Anqi

    2015-01-01

    The human brain, especially the prefrontal cortex (PFC), is functionally and anatomically reorganized in order to adapt to neuronal challenges in aging. This study employed structural MRI, resting-state fMRI (rs-fMRI), and high angular resolution diffusion imaging (HARDI), and examined the functional and structural reorganization of the PFC in aging using a Chinese sample of 173 subjects aged from 21 years and above. We found age-related increases in the structural connectivity between the PFC and posterior brain regions. Such findings were partially mediated by age-related increases in the structural connectivity of the occipital lobe within the posterior brain. Based on our findings, it is thought that the PFC reorganization in aging could be partly due to the adaptation to age-related changes in the structural reorganization of the posterior brain. This thus supports the idea derived from task-based fMRI that the PFC reorganization in aging may be adapted to the need of compensation for resolving less distinctive stimulus information from the posterior brain regions. In addition, we found that the structural connectivity of the PFC with the temporal lobe was fully mediated by the temporal cortical thickness, suggesting that the brain morphology plays an important role in the functional and structural reorganization with aging.

  6. Adaptation of brain functional and structural networks in aging.

    Directory of Open Access Journals (Sweden)

    Annie Lee

    Full Text Available The human brain, especially the prefrontal cortex (PFC, is functionally and anatomically reorganized in order to adapt to neuronal challenges in aging. This study employed structural MRI, resting-state fMRI (rs-fMRI, and high angular resolution diffusion imaging (HARDI, and examined the functional and structural reorganization of the PFC in aging using a Chinese sample of 173 subjects aged from 21 years and above. We found age-related increases in the structural connectivity between the PFC and posterior brain regions. Such findings were partially mediated by age-related increases in the structural connectivity of the occipital lobe within the posterior brain. Based on our findings, it is thought that the PFC reorganization in aging could be partly due to the adaptation to age-related changes in the structural reorganization of the posterior brain. This thus supports the idea derived from task-based fMRI that the PFC reorganization in aging may be adapted to the need of compensation for resolving less distinctive stimulus information from the posterior brain regions. In addition, we found that the structural connectivity of the PFC with the temporal lobe was fully mediated by the temporal cortical thickness, suggesting that the brain morphology plays an important role in the functional and structural reorganization with aging.

  7. Structural aging program -- a summary of activities, results, and conclusions

    Energy Technology Data Exchange (ETDEWEB)

    Naus, D.J.; Oland, C.B. [Oak Ridge National Lab., TN (United States); Ellingwood, B.R. [Johns Hopkins Univ., Baltimore, MD (United States)] [and others

    1997-01-01

    Research has been conducted by the Oak Ridge National Laboratory to address aging management of nuclear power plant concrete structures. The purpose was to identify potential structural safety issues and acceptance criteria for use in continued service assessments. Primary program accomplishments have included formulation of a Structural Materials Information Center that contains data and information on the time variation of material properties under the influence of pertinent environmental stressors and aging factors for 144 materials, an aging assessment methodology to identify critical structures and degradation factors that can potentially impact their performance, guidelines and evaluation criteria for use in condition assessments of reinforced concrete structures, and a reliability-based methodology for current condition assessments and estimations of future performance of reinforced concrete nuclear power plant structures. In addition, the Structural Aging Program conducted in-depth evaluations of several nondestructive evaluation and repair-related technologies to develop guidance on their applicability.

  8. Mechanisms Underlying T Cell Immunosenescence: Aging and Cytomegalovirus Infection

    Science.gov (United States)

    Tu, Wenjuan; Rao, Sudha

    2016-01-01

    The ability of the human immune system to protect against infectious disease declines with age and efficacy of vaccination reduces significantly in the elderly. Aging of the immune system, also termed as immunosenescence, involves many changes in human T cell immunity that is characterized by a loss in naïve T cell population and an increase in highly differentiated CD28- memory T cell subset. There is extensive data showing that latent persistent human cytomegalovirus (HCMV) infection is also associated with age-related immune dysfunction in the T cells, which might enhance immunosenescence. Understanding the molecular mechanisms underlying age-related and HCMV-related immunosenescence is critical for the development of effective age-targeted vaccines and immunotherapies. In this review, we will address the role of both aging and HCMV infection that contribute to the T cell senescence and discuss the potential molecular mechanisms in aged T cells. PMID:28082969

  9. Structural and ideological voting in age cohorts

    NARCIS (Netherlands)

    van der Brug, W.

    2010-01-01

    In most West European countries the effects of long-term determinants of the vote − in particular social class, religion and left-right ideology − have slowly weakened since the late 1980s. This paper first describes differences between the EU member states in the extent of structural and ideologica

  10. Cell Structure Study.

    Science.gov (United States)

    Ekstrom, James V.

    2000-01-01

    Presents an activity in which students use microscopes and digital images to examine Elodea, a fresh water plant, before and after the process of plasmolysis, identify plant cellular structures before and after plasmolysis, and calculate the size of the plant's vacuole. (ASK)

  11. AGE STRUCTURES OF MODULES OF CLONAL PEATLAND SEDGE Carex middendorffii

    Institute of Scientific and Technical Information of China (English)

    BU Zhao-jun; YANG Yun-fei; H(a)kan RYDIN; LANG Hui-qing

    2005-01-01

    Age structure of a plant population carries important information on population dynamics. The traditional age classification of individuals by development phases could not explain the generation relationship neither between individuals nor between modules, and it could not accurately predict the future of population or the tendency of peatland evolution. In a peatland of the Xiao Hinggan Mountains, China, at the middle of the growth season,the age structures of 3 modules, ramets, active buds and rhizomes of a Carex middendo(fii clonal population were investigated, with the method of classifying age classes of ramets and active buds by counting generation quantity of tiller nodes, and classifying age classes of rhizomes by their real survival time. The quantity of vegetative ramets was dominant. Tiller nodes oframets can propagate vegetatively for a maximum of 3 generations. The population of ramets consisted of 3 age classes of ramets at the middle of the growth season, and showed a stable age structure. In the two sampling events, there was no significant difference between quantities and age structure of the population.The maximum age of an excavated rhizome was 12 years old. Rhizomes were classified in 8 age classes, and age classes 4-6 contributed most to the total biomass. There was no significant difference in total length and total biomass per unit area, or in biomass per unit length in rhizomes between the two samplings. Four age classes of active buds were recognized, and their number increased from July to August. The Carex middendorffii clonal population achieved regeneration by budding from the tiller nodes of ramets. The age structures of the 3 modules suggested that the Carex middendorffii clonal population could persist in the early development phase of the oligotrophic peatland in the Xiao Hinggan Mountains, but it could not be dominant. It also faces the risk to disappear from the community as the peatland develops further.

  12. The Hyades distance, structure, dynamics, and age

    CERN Document Server

    Perryman, M A C; Lebreton, Y; Gómez, A; Turon, C; De Strobel, G C; Mermilliod, J C; Robichon, N; Kovalevsky, J; Crifo, F

    1997-01-01

    We use absolute trigonometric parallaxes from the Hipparcos Catalogue to determine individual distances to members of the Hyades cluster, from which the 3-dimensional structure of the cluster can be derived. Inertially-referenced proper motions are used to rediscuss distance determinations based on convergent-point analyses. A combination of parallaxes and proper motions from Hipparcos, and radial velocities from ground-based observations, are used to determine the position and velocity components of candidate members with respect to the cluster centre, providing new information on cluster membership: 13 new candidate members within 20 pc of the cluster centre have been identified. Farther from the cluster centre there is a gradual merging between certain cluster members and field stars, both spatially and kinematically. Within the cluster, the kinematical structure is fully consistent with parallel space motion of the component stars with an internal velocity dispersion of about 0.3 km/s. The spatial structu...

  13. Defective TFH Cell Function and Increased TFR Cells Contribute to Defective Antibody Production in Aging.

    Science.gov (United States)

    Sage, Peter T; Tan, Catherine L; Freeman, Gordon J; Haigis, Marcia; Sharpe, Arlene H

    2015-07-14

    Defective antibody production in aging is broadly attributed to immunosenescence. However, the precise immunological mechanisms remain unclear. Here, we demonstrate an increase in the ratio of inhibitory T follicular regulatory (TFR) cells to stimulatory T follicular helper (TFH) cells in aged mice. Aged TFH and TFR cells are phenotypically distinct from those in young mice, exhibiting increased programmed cell death protein-1 expression but decreased ICOS expression. Aged TFH cells exhibit defective antigen-specific responses, and programmed cell death protein-ligand 1 blockade can partially rescue TFH cell function. In contrast, young and aged TFR cells have similar suppressive capacity on a per-cell basis in vitro and in vivo. Together, these studies reveal mechanisms contributing to defective humoral immunity in aging: an increase in suppressive TFR cells combined with impaired function of aged TFH cells results in reduced T-cell-dependent antibody responses in aged mice.

  14. Defective TFH Cell Function and Increased TFR Cells Contribute to Defective Antibody Production in Aging

    Directory of Open Access Journals (Sweden)

    Peter T. Sage

    2015-07-01

    Full Text Available Defective antibody production in aging is broadly attributed to immunosenescence. However, the precise immunological mechanisms remain unclear. Here, we demonstrate an increase in the ratio of inhibitory T follicular regulatory (TFR cells to stimulatory T follicular helper (TFH cells in aged mice. Aged TFH and TFR cells are phenotypically distinct from those in young mice, exhibiting increased programmed cell death protein-1 expression but decreased ICOS expression. Aged TFH cells exhibit defective antigen-specific responses, and programmed cell death protein-ligand 1 blockade can partially rescue TFH cell function. In contrast, young and aged TFR cells have similar suppressive capacity on a per-cell basis in vitro and in vivo. Together, these studies reveal mechanisms contributing to defective humoral immunity in aging: an increase in suppressive TFR cells combined with impaired function of aged TFH cells results in reduced T-cell-dependent antibody responses in aged mice.

  15. Aging, Clonality, and Rejuvenation of Hematopoietic Stem Cells.

    Science.gov (United States)

    Akunuru, Shailaja; Geiger, Hartmut

    2016-08-01

    Aging is associated with reduced organ function and increased disease incidence. Hematopoietic stem cell (HSC) aging driven by both cell intrinsic and extrinsic factors is linked to impaired HSC self-renewal and regeneration, aging-associated immune remodeling, and increased leukemia incidence. Compromised DNA damage responses and the increased production of reactive oxygen species (ROS) have been previously causatively attributed to HSC aging. However, recent paradigm-shifting concepts, such as global epigenetic and cytoskeletal polarity shifts, cellular senescence, as well as the clonal selection of HSCs upon aging, provide new insights into HSC aging mechanisms. Rejuvenating agents that can reprogram the epigenetic status of aged HSCs or senolytic drugs that selectively deplete senescent cells provide promising translational avenues for attenuating hematopoietic aging and, potentially, alleviating aging-associated immune remodeling and myeloid malignancies.

  16. Aging of hematopoietic stem cells: DNA damage and mutations?

    Science.gov (United States)

    Moehrle, Bettina M; Geiger, Hartmut

    2016-10-01

    Aging in the hematopoietic system and the stem cell niche contributes to aging-associated phenotypes of hematopoietic stem cells (HSCs), including leukemia and aging-associated immune remodeling. Among others, the DNA damage theory of aging of HSCs is well established, based on the detection of a significantly larger amount of γH2AX foci and a higher tail moment in the comet assay, both initially thought to be associated with DNA damage in aged HSCs compared with young cells, and bone marrow failure in animals devoid of DNA repair factors. Novel data on the increase in and nature of DNA mutations in the hematopoietic system with age, the quality of the DNA damage response in aged HSCs, and the nature of γH2AX foci question a direct link between DNA damage and the DNA damage response and aging of HSCs, and rather favor changes in epigenetics, splicing-factors or three-dimensional architecture of the cell as major cell intrinsic factors of HSCs aging. Aging of HSCs is also driven by a strong contribution of aging of the niche. This review discusses the DNA damage theory of HSC aging in the light of these novel mechanisms of aging of HSCs.

  17. Role of adenohypophyseal mixed cell-follicles in age estimation.

    Directory of Open Access Journals (Sweden)

    Ishikawa T

    2003-04-01

    Full Text Available In this study we used paraffin-embedded human pituitary obtained from 248 autopsy cases and identified mixed cell follicles by the immunohistochemical method. We examined the number and size of the mixed cell follicles, and the ratio of each component cell of these follicles, in the anterior pituitary at various age groups. The number of follicles increased with age, and the size of the follicles also tended to enlarge with age. Statistical analysis showed that a high correlation existed between age and the number or the size of the mixed cell-follicles formed by various adenohypophyseal cells. In addition, when the proportions of the different cell types that formed the follicles were examined, sex differences were observed with aging for the GH cells, the PRL cells, and the gonadotroph (GTH cells, while no changes were observed with aging in both men and women for the ACTH cells and TSH cells. These results indicate that the number, size, and ratio of each component cell of follicles in the anterior pituitary are adequately applicable for the purpose of age estimation in routine forensic medicine.

  18. Aging of perennial cells and organ parts according to the programmed aging paradigm.

    Science.gov (United States)

    Libertini, Giacinto; Ferrara, Nicola

    2016-04-01

    If aging is a physiological phenomenon-as maintained by the programmed aging paradigm-it must be caused by specific genetically determined and regulated mechanisms, which must be confirmed by evidence. Within the programmed aging paradigm, a complete proposal starts from the observation that cells, tissues, and organs show continuous turnover: As telomere shortening determines both limits to cell replication and a progressive impairment of cellular functions, a progressive decline in age-related fitness decline (i.e., aging) is a clear consequence. Against this hypothesis, a critic might argue that there are cells (most types of neurons) and organ parts (crystalline core and tooth enamel) that have no turnover and are subject to wear or manifest alterations similar to those of cells with turnover. In this review, it is shown how cell types without turnover appear to be strictly dependent on cells subjected to turnover. The loss or weakening of the functions fulfilled by these cells with turnover, due to telomere shortening and turnover slowing, compromises the vitality of the served cells without turnover. This determines well-known clinical manifestations, which in their early forms are described as distinct diseases (e.g., Alzheimer's disease, Parkinson's disease, age-related macular degeneration, etc.). Moreover, for the two organ parts (crystalline core and tooth enamel) without viable cells or any cell turnover, it is discussed how this is entirely compatible with the programmed aging paradigm.

  19. Telomere attrition in beta and alpha cells with age.

    Science.gov (United States)

    Tamura, Yoshiaki; Izumiyama-Shimomura, Naotaka; Kimbara, Yoshiyuki; Nakamura, Ken-Ichi; Ishikawa, Naoshi; Aida, Junko; Chiba, Yuko; Matsuda, Yoko; Mori, Seijiro; Arai, Tomio; Fujiwara, Mutsunori; Poon, Steven S S; Ishizaki, Tatsuro; Araki, Atsushi; Takubo, Kaiyo; Ito, Hideki

    2016-06-01

    We have reported telomere attrition in β and α cells of the pancreas in elderly patients with type 2 diabetes, but it has not been explored how the telomere lengths of these islet cells change according to age in normal subjects. To examine the telomere lengths of β and α cells in individuals without diabetes across a wide range of ages, we conducted measurement of the telomere lengths of human pancreatic β and α cells obtained from 104 autopsied subjects without diabetes ranging in age from 0 to 100 years. As an index of telomere lengths, the normalized telomere-centromere ratio (NTCR) was determined for β (NTCRβ) and α (NTCRα) cells by quantitative fluorescence in situ hybridization (Q-FISH). We found NTCRβ and NTCRα showed almost the same levels and both decreased according to age (p telomeres of β and α cells become shortened with normal aging process.

  20. Hematopoietic stem cells : Self-renewing or aging?

    NARCIS (Netherlands)

    de Haan, G

    2002-01-01

    Stem cells are defined by their extensive self-renewal properties, and yet there is abundant evidence of erosion of stem cell functioning during aging. Whereas intracellular repair and protection mechanisms determine the lifespan of an individual cell, here an argument is made that somatic stem cell

  1. Corrugated Membrane Fuel Cell Structures

    Energy Technology Data Exchange (ETDEWEB)

    Grot, Stephen [President, Ion Power Inc.

    2013-09-30

    One of the most challenging aspects of traditional PEM fuel cell stacks is the difficulty achieving the platinum catalyst utilization target of 0.2 gPt/kWe set forth by the DOE. Good catalyst utilization can be achieved with state-of-the-art catalyst coated membranes (CCM) when low catalyst loadings (<0.3 mg/cm2) are used at a low current. However, when low platinum loadings are used, the peak power density is lower than conventional loadings, requiring a larger total active area and a larger bipolar plate. This results in a lower overall stack power density not meeting the DOE target. By corrugating the fuel cell membrane electrode structure, Ion Power?s goal is to realize both the Pt utilization targets as well as the power density targets of the DOE. This will be achieved by demonstrating a fuel cell single cell (50 cm2) with a twofold increase in the membrane active area over the geometric area of the cell by corrugating the MEA structure. The corrugating structure must be able to demonstrate the target properties of < 10 mOhm-cm2 electrical resistance at > 20 psi compressive strength over the active area, in combination with offering at least 80% of power density that can be achieved by using the same MEA in a flat plate structure. Corrugated membrane fuel cell structures also have the potential to meet DOE power density targets by essentially packaging more membrane area into the same fuel cell volume as compared to conventional stack constructions.

  2. Demographic analysis from summaries of an age-structured population

    Science.gov (United States)

    Link, William A.; Royle, J. Andrew; Hatfield, Jeff S.

    2003-01-01

    Demographic analyses of age-structured populations typically rely on life history data for individuals, or when individual animals are not identified, on information about the numbers of individuals in each age class through time. While it is usually difficult to determine the age class of a randomly encountered individual, it is often the case that the individual can be readily and reliably assigned to one of a set of age classes. For example, it is often possible to distinguish first-year from older birds. In such cases, the population age structure can be regarded as a latent variable governed by a process prior, and the data as summaries of this latent structure. In this article, we consider the problem of uncovering the latent structure and estimating process parameters from summaries of age class information. We present a demographic analysis for the critically endangered migratory population of whooping cranes (Grus americana), based only on counts of first-year birds and of older birds. We estimate age and year-specific survival rates. We address the controversial issue of whether management action on the breeding grounds has influenced recruitment, relating recruitment rates to the number of seventh-year and older birds, and examining the pattern of variation through time in this rate.

  3. Dynamic changes in mouse hematopoietic stem cell numbers during aging

    NARCIS (Netherlands)

    de Haan, G; Van Zant, G

    1999-01-01

    To address the fundamental question of whether or not stem cell populations age, we performed quantitative measurements of the cycling status and frequency of hematopoietic stem cells in long-lived C57BL/6 (B6) and short-lived DBA/2 (DBA) mice at different developmental and aging stages. The frequen

  4. Stem cells as vehicles for youthful regeneration of aged tissues.

    Science.gov (United States)

    Rando, Thomas A; Wyss-Coray, Tony

    2014-06-01

    Stem cells hold great promise for regenerative therapies for a wide spectrum of diseases and disorders of aging by virtue of their ability to regenerate tissues and contribute to their homeostasis. Aging is associated with a marked decline in these functionalities of adult stem cells. As such, regeneration of aged tissues is both less efficient and less effective than that of young tissues. Recent studies have revealed the remarkably dynamic responses of stem cells to systemic signals, including the ability of "youthful" factors in the blood of young animals to enhance the functionality of aged stem cells. Thus, there is much hope that even aged stem cells retain a remarkable regenerative potential if provided with the correct cues and environment to engage in tissue repair. The overall focus of the presentations of this session is to address the determinants of changes in stem cell functionality with age, the key characteristics of stem cells in aged tissues, the extent to which those characteristics are capable of being rejuvenated and by what signals, and the potential for stem cell therapeutics for chronic diseases and acute injuries in aged individuals.

  5. Molecular aging and rejuvenation of human muscle stem cells

    DEFF Research Database (Denmark)

    Carlson, Morgan E; Suetta, Charlotte; Conboy, Michael J

    2009-01-01

    Very little remains known about the regulation of human organ stem cells (in general, and during the aging process), and most previous data were collected in short-lived rodents. We examined whether stem cell aging in rodents could be extrapolated to genetically and environmentally variable humans....... Our findings establish key evolutionarily conserved mechanisms of human stem cell aging. We find that satellite cells are maintained in aged human skeletal muscle, but fail to activate in response to muscle attrition, due to diminished activation of Notch compounded by elevated transforming growth...... factor beta (TGF-beta)/phospho Smad3 (pSmad3). Furthermore, this work reveals that mitogen-activated protein kinase (MAPK)/phosphate extracellular signal-regulated kinase (pERK) signalling declines in human muscle with age, and is important for activating Notch in human muscle stem cells. This molecular...

  6. Aging and demographic plasticity in response to experimental age structures in honeybees (Apis mellifera L).

    Science.gov (United States)

    Rueppell, Olav; Linford, Robyn; Gardner, Preston; Coleman, Jennifer; Fine, Kari

    2008-08-01

    Honeybee colonies are highly integrated functional units characterized by a pronounced division of labor. Division of labor among workers is mainly age-based, with younger individuals focusing on in-hive tasks and older workers performing the more hazardous foraging activities. Thus, experimental disruption of the age composition of the worker hive population is expected to have profound consequences for colony function. Adaptive demography theory predicts that the natural hive age composition represents a colony-level adaptation and thus results in optimal hive performance. Alternatively, the hive age composition may be an epiphenomenon, resulting from individual life history optimization. We addressed these predictions by comparing individual worker longevity and brood production in hives that were composed of a single age cohort, two distinct age cohorts, and hives that had a continuous, natural age distribution. Four experimental replicates showed that colonies with a natural age composition did not consistently have a higher life expectancy and/or brood production than the single cohort or double cohort hives. Instead, a complex interplay of age structure, environmental conditions, colony size, brood production, and individual mortality emerged. A general trade-off between worker life expectancy and colony productivity was apparent, and the transition from in-hive tasks to foraging was the most significant predictor of worker lifespan irrespective of the colony age structure. We conclude that the natural age structure of honeybee hives is not a colony-level adaptation. Furthermore, our results show that honeybees exhibit pronounced demographic plasticity in addition to behavioral plasticity to react to demographic disturbances of their societies.

  7. Structural developmental psychology and health promotion in the third age.

    Science.gov (United States)

    Bauger, Lars; Bongaardt, Rob

    2017-01-12

    In response to the ever-increasing longevity in Western societies, old age has been divided into two different periods, labelled the third and fourth age. Where the third age, with its onset at retirement, mostly involves positive aspects of growing old, the fourth age involves functional decline and increased morbidity. This article focuses on the entry to the third age and its potential for health promotion initiatives. Well-being is an important factor to emphasize in such health promotion, and this article views the lifestyle of third agers as essential for their well-being. The structural developmental theory of Robert Kegan delineates how a person's way of knowing develops throughout the life course. This theory is an untapped and salient perspective for health promotion initiatives in the third age. This article outlines Kegan's approach as a tool for developing psychologically spacious health promotion, and suggests future directions for research on the topic.

  8. ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases

    Directory of Open Access Journals (Sweden)

    Pierpaola Davalli

    2016-01-01

    Full Text Available The aging process worsens the human body functions at multiple levels, thus causing its gradual decrease to resist stress, damage, and disease. Besides changes in gene expression and metabolic control, the aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS and/or Reactive Nitrosative Species (RNS. Specific increases of ROS level have been demonstrated as potentially critical for induction and maintenance of cell senescence process. Causal connection between ROS, aging, age-related pathologies, and cell senescence is studied intensely. Senescent cells have been proposed as a target for interventions to delay the aging and its related diseases or to improve the diseases treatment. Therapeutic interventions towards senescent cells might allow restoring the health and curing the diseases that share basal processes, rather than curing each disease in separate and symptomatic way. Here, we review observations on ROS ability of inducing cell senescence through novel mechanisms that underpin aging processes. Particular emphasis is addressed to the novel mechanisms of ROS involvement in epigenetic regulation of cell senescence and aging, with the aim to individuate specific pathways, which might promote healthy lifespan and improve aging.

  9. Modeling cell-in-cell structure into its biological significance

    OpenAIRE

    He, M-f; Wang, S.; Wang, Y; Wang, X-N.

    2013-01-01

    Although cell-in-cell structure was noted 100 years ago, the molecular mechanisms of ‘entering' and the destination of cell-in-cell remain largely unclear. It takes place among the same type of cells (homotypic cell-in-cell) or different types of cells (heterotypic cell-in-cell). Cell-in-cell formation affects both effector cells and their host cells in multiple aspects, while cell-in-cell death is under more intensive investigation. Given that cell-in-cell has an important role in maintainin...

  10. Analysis on age structure of Zoysia japonica(Poaceae) population

    Institute of Scientific and Technical Information of China (English)

    WANGYan; DAIBao-qing; LIANGYong-jun; MALian-ju

    2003-01-01

    The age-structure of natural population of Zoysia japonica in Xiuyan County of Liaoning Province was studied by generational method.The results showed that the highest tiller age class was three,but 1st age class tillers held dominant position with proportions over 95% in each month during the growing seasons.The 2nd age class and 2rd age class tillers were minority in the population.So Z.japonica population was an expanding population.The zero age class buds on the rhizomes were dominantin buds age structures.The proportion of buds to tillers on quantity in each month was about 30% to 40% and reached the highest at the end of September.The increasing of buds proportion before dormancy guaranteed the quantity of tillers in the next spring.The biomass of 1st age class tillers changed with time.The biomass kept increasing from April to July and reached the highest at the end of July and then decreased.

  11. The structure and function of fungal cells

    Science.gov (United States)

    Nozawa, Y.

    1984-01-01

    The structure and function of fungal cell walls were studied with particular emphasis on dermatophytes. Extraction, isolation, analysis, and observation of the cell wall structure and function were performed. The structure is described microscopically and chemically.

  12. Density dependence in an age-structured population of great tits: identifying the critical age classes.

    Science.gov (United States)

    Gamelon, Marlène; Grøtan, Vidar; Engen, Steinar; Bjørkvoll, Eirin; Visser, Marcel E; Saether, Bernt-Erik

    2016-09-01

    Classical approaches for the analyses of density dependence assume that all the individuals in a population equally respond and equally contribute to density dependence. However, in age-structured populations, individuals of different ages may differ in their responses to changes in population size and how they contribute to density dependence affecting the growth rate of the whole population. Here we apply the concept of critical age classes, i.e., a specific scalar function that describes how one or a combination of several age classes affect the demographic rates negatively, in order to examine how total density dependence acting on the population growth rate depends on the age-specific population sizes. In a 38-yr dataset of an age-structured great tit (Parus major) population, we find that the age classes, including the youngest breeding females, were the critical age classes for density regulation. These age classes correspond to new breeders that attempt to take a territory and that have the strongest competitive effect on other breeding females. They strongly affected population growth rate and reduced recruitment and survival rates of all breeding females. We also show that depending on their age class, females may differently respond to varying density. In particular, the negative effect of the number of breeding females was stronger on recruitment rate of the youngest breeding females. These findings question the classical assumptions that all the individuals of a population can be treated as having an equal contribution to density regulation and that the effect of the number of individuals is age independent. Our results improve our understanding of density regulation in natural populations.

  13. Structural Aging Program approach to providing an improved basis for aging management of safety-related concrete structures

    Energy Technology Data Exchange (ETDEWEB)

    Naus, D.J.; Oland, C.B. [Oak Ridge National Lab., TN (United States); Ellingwood, B. [Johns Hopkins Univ., Baltimore, MD (United States)

    1993-11-01

    The Structural Aging (SAG) Program is being conducted at the Oak Ridge National Laboratory (ORNL) for the United States Nuclear Regulatory Commission (USNRC). The SAG Program is addressing the aging management of safety-related concrete structures in nuclear power plants for the purpose of providing improved technical bases for their continued service. The program is organized into four tasks: Program Management, Materials Property Data Base, Structural Component Assessment/Repair Technologies, and Quantitative Methodology for Continued Service Determinations. Objectives and a summary of recent accomplishments under each of these tasks are presented.

  14. Stem cells: Potential therapy for age-related diseases

    DEFF Research Database (Denmark)

    Kassem, Moustapha

    2006-01-01

    Aging is associated with a progressive failing of tissues and organs of the human body leading to a large number of age-related diseases. Regenerative medicine is an emerging clinical discipline that aims to employ cellular medicines (normal cells, ex vivo expanded cells, or tissue......-engineered organs) to restore the functions of damaged or defective tissues and organs and thus to "rejuvenate" the failing aging body. One of the most important sources for cellular medicine is embryonic and adult (somatic) stem cells (SSCs). One example of SCCs with enormous clinical potential is the mesenchymal...... stem cells (MSCs) that are present in the bone marrow and are able to differentiate into cell types such as osteoblasts, chondrocytes, endothelial cells, and probably also neuron-like cells. Because of the ease of their isolation and their extensive differentiation potential, MSCs are among the first...

  15. Thalamic structures and associated cognitive functions: Relations with age and aging

    Science.gov (United States)

    Fama, Rosemary; Sullivan, Edith V.

    2015-01-01

    The thalamus, with its cortical, subcortical, and cerebellar connections, is a critical node in networks supporting cognitive functions known to decline in normal aging, including component processes of memory and executive functions of attention and information processing. The macrostructure, microstructure, and neural connectivity of the thalamus changes across the adult lifespan. Structural and functional magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) have demonstrated, regional thalamic volume shrinkage and microstructural degradation, with anterior regions generally more compromised than posterior regions. The integrity of selective thalamic nuclei and projections decline with advancing age, particularly those in thalamofrontal, thalamoparietal, and thalamolimbic networks. This review presents studies that assess the relations between age and aging and the structure, function, and connectivity of the thalamus and associated neural networks and focuses on their relations with processes of attention, speed of information processing, and working and episodic memory. PMID:25862940

  16. Report on aging of nuclear power plant reinforced concrete structures

    Energy Technology Data Exchange (ETDEWEB)

    Naus, D.J.; Oland, C.B. [Oak Ridge National Lab., TN (United States); Ellingwood, B.R. [Johns Hopkins Univ., Baltimore, MD (United States). Dept. of Civil Engineering

    1996-03-01

    The Structural Aging Program provides the US Nuclear Regulatory Commission with potential structural safety issues and acceptance criteria for use in continued service assessments of nuclear power plant safety-related concrete structures. The program was organized under four task areas: Program Management, Materials Property Data Base, Structural Component Assessment/Repair Technology, and Quantitative Methodology for Continued Service Determinations. Under these tasks, over 90 papers and reports were prepared addressing pertinent aspects associated with aging management of nuclear power plant reinforced concrete structures. Contained in this report is a summary of program results in the form of information related to longevity of nuclear power plant reinforced concrete structures, a Structural Materials Information Center presenting data and information on the time variation of concrete materials under the influence of environmental stressors and aging factors, in-service inspection and condition assessments techniques, repair materials and methods, evaluation of nuclear power plant reinforced concrete structures, and a reliability-based methodology for current and future condition assessments. Recommendations for future activities are also provided. 308 refs., 61 figs., 50 tabs.

  17. Effect of curcumin on aging retinal pigment epithelial cells

    Directory of Open Access Journals (Sweden)

    Zhu W

    2015-09-01

    Full Text Available Wei Zhu,1,* Yan Wu,2,* Yi-Fang Meng,1 Jin-Yu Wang,1 Ming Xu,1 Jian-Jun Tao,1 Jiong Lu1 1Department of Ophthalmology, Changshu No 2 People’s Hospital, Changshu, 2Department of Ophthalmology, The First People’s Hospital of Kunshan Affiliated with Jiangsu University, Suzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Age-related macular degeneration (AMD is now one of the leading causes of blindness in the elderly population. The antioxidative effects of curcumin on aging retinal pigment epithelial (RPE cells are still unclear. We conducted an in vitro study to investigate the effects of curcumin on aging RPE cells. A pulsed H2O2 exposure aging model was adopted. Aging RPE cells were treated with curcumin 20 µM, 40 µM, and 80 µM. Apoptosis of RPE cells was analyzed by flow cytometry. The intracellular reactive oxygen species concentration was detected using a specific probe and apoptosis-associated proteins were detected by Western blot. Expression of oxidative biomarkers, including superoxide dismutase, maleic dialdehyde, and glutathione, was detected commercially available assay kits. Compared with normal cells, lower cell viability, higher apoptosis rates, and more severe oxidation status were identified in the aging RPE cell model. Curcumin improved cell viability and decreased apoptosis and oxidative stress. Further, curcumin had a significant influence on expression of apoptosis-associated proteins and oxidative stress biomarkers. In conclusion, treatment with curcumin was able to regulate proliferation, oxidative stress, and apoptosis in aging RPE cells. Accordingly, application of curcumin may be a novel strategy to protect against age-related change in AMD. Keywords: curcumin, retinal pigment epithelium, apoptosis, age-related macular degeneration

  18. Cell ageing: a flourishing field for neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Dora Brites

    2015-06-01

    Full Text Available Cellular senescence is viewed as an irreversible cell-cycle arrest mechanism involving a complexity of biological progressive processes and the acquisition of diverse cellular phenotypes. Several cell-intrinsic and extrinsic causes (stresses may lead to diverse cellular signaling cascades that include oxidative stress, mitochondrial dysfunction, DNA damage, excessive accumulation of misfolded proteins, impaired microRNA processing and inflammation. Here we review recent advances in the causes and consequences of brain cell ageing, including the senescence of endothelial cells at the central nervous system barriers, as well as of neurons and glial cells. We address what makes ageing an important risk factor for neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and cerebrovascular disease. In particular, we highlight the importance of defects in mitochondrial dynamics, in the cathepsin activity imbalance, in cell-cell communication, in the accumulation of misfolded and unfolded proteins and in the microRNA profiling as having potential impact on cellular ageing processes. Another important aspect is that the absence of specific senescence biomarkers has hampered the characterization of senescent cells in ageing and age-associated diseases. In accordance, the senescence-associated secretory phenotype (SASP or secretome was shown to vary in distinct cell types and upon different stressors, and SASP heterogeneity is believed to create subsets of senenescent cells. In addition to secreted proteins, we then place extracellular vesicles (exosomes and ectosomes as important mediators of intercellular communication with pathophysiological roles in disease spreading, and as emerging targets for therapeutic intervention. We also discuss the application of engineered extracellular vesicles as vehicles for drug delivery. Finally, we summarize current knowledge on methods to rejuvenate senescent cells

  19. Aging changes in organs - tissue - cells

    Science.gov (United States)

    ... and structure to the skin and internal organs. Epithelial tissue provides a covering for deeper body layers. The ... such as the gastrointestinal system, are made of epithelial tissue. Muscle tissue includes three types of tissue: Striated ...

  20. Mind-Reading Ability and Structural Connectivity Changes in Aging.

    Science.gov (United States)

    Cabinio, Monia; Rossetto, Federica; Blasi, Valeria; Savazzi, Federica; Castelli, Ilaria; Massaro, Davide; Valle, Annalisa; Nemni, Raffaello; Clerici, Mario; Marchetti, Antonella; Baglio, Francesca

    2015-01-01

    The Mind-Reading ability through the eyes is an important component of the affective Theory of Mind (ToM), which allows people to infer the other's mental state from the eye gaze. The aim of the present study was to investigate to which extent age-associated structural brain changes impact this ability and to determine if this association is related to executive functions in elderly subjects. For this purpose, Magnetic Resonance Imaging was used to determine both gray matter and white matter (WM) areas associated with aging. The resulting areas have been included in a subsequent correlation analysis to detect the brain regions whose structure was associated with the Mind-Reading ability through the eyes, assessed with the Italian version of the "Reading the Mind in the Eyes" (RME) test, in a sample of 36 healthy subjects ranging from 24 to 79 years of age. The analysis resulted in three important findings: (1) the performance to the RME test is relatively stable across the decades 20-70 (despite a slight decrease of this ability with aging) and independent from executive functions; (2) structural brain imaging demonstrated the involvement of a great number of cortical ToM areas for the execution of the RME test: the bilateral precentral gyrus, the bilateral posterior insula, the left superior temporal gyrus and the left inferior frontal gyrus, which also showed a significant volume decrease with age; (3) an age and task-related decline in WM connectivity on left fronto-temporal portion of the brain. Our results confirm the age-related structural modifications of the brain and show that these changes have an influence on the Mind-Reading ability through the eyes.

  1. Mind-Reading ability and structural connectivity changes in aging

    Directory of Open Access Journals (Sweden)

    Monia eCabinio

    2015-11-01

    Full Text Available The Mind-Reading ability through the eyes is an important component of the affective Theory of Mind (ToM, which allows people to infer the other’s mental state from the eye gaze. The aim of the present study was to investigate to which extent age-associated structural brain changes impact this ability and to determine if this association is related to executive functions in elderly subjects. For this purpose, Magnetic Resonance Imaging was used to determine both gray matter and white matter areas associated with aging. The resulting areas have been included in a subsequent correlation analysis to detect the brain regions whose structure was associated with the Mind-Reading ability through the eyes, assessed with the Italian version of the Reading the Mind in the Eyes (RME test, in a sample of 36 healthy subjects ranging from 24 to 79 years of age. The analysis resulted in three important findings: 1 the performance to the RME test is relatively stable across the decades 20-70 (despite a slight decrease of this ability with aging and independent from executive functions; 2 structural brain imaging demonstrated the involvement of a great number of cortical ToM areas for the execution of the RME test: the bilateral precentral gyrus, the bilateral posterior insula, the left superior temporal gyrus and the left inferior frontal gyrus, which also showed a significant volume decrease with age; 3 an age and task-related decline in white matter connectivity on left fronto-temporal portion of the brain. Our results confirm the age-related structural modifications of the brain and show that these changes have an influence on the Mind-Reading ability through the eyes.

  2. Path dependence of lithium ion cells aging under storage conditions

    Science.gov (United States)

    Su, Laisuo; Zhang, Jianbo; Huang, Jun; Ge, Hao; Li, Zhe; Xie, Fengchao; Liaw, Bor Yann

    2016-05-01

    This work investigates path dependence of lithium ion cells that are stored under static and non-static conditions. In the static storage tests, the levels of temperature and state of charge (SOC) are kept constant. The results of 12 tests from a combination of three temperatures and four SOCs show that, as expected, the cell ages faster at higher temperature and higher SOC. However, the cell aging mode, while consistent for all the evaluated temperatures, is different at 95% SOC from that at lower SOCs. In the non-static storage tests, the levels of temperature and SOC vary with time during the test process. The effect of the sequence of stress levels on cell aging is studied statistically using the statistical method of analysis of variation (ANOVA). It is found that cell capacity fade is path independent of both SOC and temperature, while cell resistance increase is path dependent on SOC and path independent of temperature. Finally, rate-based empirical aging models are adopted to fit the cell aging in the static storage tests. The aging model for capacity fade is demonstrated to be applicable to the non-static tests with errors between -3% and +3% for all the tested conditions over 180 days.

  3. An age-structured extension to the vectorial capacity model.

    Directory of Open Access Journals (Sweden)

    Vasiliy N Novoseltsev

    Full Text Available BACKGROUND: Vectorial capacity and the basic reproductive number (R(0 have been instrumental in structuring thinking about vector-borne pathogen transmission and how best to prevent the diseases they cause. One of the more important simplifying assumptions of these models is age-independent vector mortality. A growing body of evidence indicates that insect vectors exhibit age-dependent mortality, which can have strong and varied affects on pathogen transmission dynamics and strategies for disease prevention. METHODOLOGY/PRINCIPAL FINDINGS: Based on survival analysis we derived new equations for vectorial capacity and R(0 that are valid for any pattern of age-dependent (or age-independent vector mortality and explore the behavior of the models across various mortality patterns. The framework we present (1 lays the groundwork for an extension and refinement of the vectorial capacity paradigm by introducing an age-structured extension to the model, (2 encourages further research on the actuarial dynamics of vectors in particular and the relationship of vector mortality to pathogen transmission in general, and (3 provides a detailed quantitative basis for understanding the relative impact of reductions in vector longevity compared to other vector-borne disease prevention strategies. CONCLUSIONS/SIGNIFICANCE: Accounting for age-dependent vector mortality in estimates of vectorial capacity and R(0 was most important when (1 vector densities are relatively low and the pattern of mortality can determine whether pathogen transmission will persist; i.e., determines whether R(0 is above or below 1, (2 vector population growth rate is relatively low and there are complex interactions between birth and death that differ fundamentally from birth-death relationships with age-independent mortality, and (3 the vector exhibits complex patterns of age-dependent mortality and R(0 ∼ 1. A limiting factor in the construction and evaluation of new age

  4. Hematopoietic stem cells and the aging hematopoietic system.

    Science.gov (United States)

    Gazit, Roi; Weissman, Irving L; Rossi, Derrick J

    2008-10-01

    The etiology of the age-associated pathophysiological changes of the hematopoietic system including the onset of anemia, diminished adaptive immune competence, and myelogenous disease development are underwritten by the loss of normal homeostatic control. As tissue and organ homeostasis in adults is primarily mediated by the activity of stem and progenitor cells, it has been suggested that the imbalances accompanying aging of the hematopoietic system may stem from alterations in the prevalence and/or functional capacity of hematopoietic stem cells (HSCs) and progenitors. In this review, we examine evidence implicating a role for stem cells in the aging of the hematopoietic system, and focus on the mechanisms suggested to contribute to stem cell aging.

  5. Adaptive evolvement of information age C4ISR structure

    Institute of Scientific and Technical Information of China (English)

    Yushi Lan; Kebo Deng; Shaojie Mao; Heng Wang; Kan Yi; Ming Lei

    2015-01-01

    Command, control, communication, computing, intel-ligence, surveil ance and reconnaissance (C4ISR) in information age is a complex system whose structure always changes ac-tively or passively during the warfare. Therefore, it is important to optimize the structure, especial y in ambiguous and quick-tempo modern warfare. This paper proposes an adaptive evolvement mechanism for the C4ISR structure to survive the changeable warfare. Firstly, the information age C4ISR structure is defined and modeled based on the complex network theory. Secondly, taking the observe, orient, decide and act (OODA) model into consideration, four kinds of loops in the C4ISR structure are pro-posed and their coefficient of networked effects (CNE) is further defined. Then, the adaptive evolvement mechanisms of the four kinds of loops are presented respectively. Final y, taking the joint air-defense C4ISR as an example, simulation experiments are im-plemented, which validate the evolvement mechanism and show that the information age C4ISR structure has some characteristics of smal-world network and scale-free network.

  6. Structural and Functional Changes With the Aging Kidney.

    Science.gov (United States)

    Denic, Aleksandar; Glassock, Richard J; Rule, Andrew D

    2016-01-01

    Senescence or normal physiologic aging portrays the expected age-related changes in the kidney as compared to a disease that occurs in some but not all individuals. The microanatomical structural changes of the kidney with older age include a decreased number of functional glomeruli from an increased prevalence of nephrosclerosis (arteriosclerosis, glomerulosclerosis, and tubular atrophy with interstitial fibrosis), and to some extent, compensatory hypertrophy of remaining nephrons. Among the macroanatomical structural changes, older age associates with smaller cortical volume, larger medullary volume until middle age, and larger and more numerous kidney cysts. Among carefully screened healthy kidney donors, glomerular filtration rate (GFR) declines at a rate of 6.3 mL/min/1.73 m(2) per decade. There is reason to be concerned that the elderly are being misdiagnosed with CKD. Besides this expected kidney function decline, the lowest risk of mortality is at a GFR of ≥75 mL/min/1.73 m(2) for age kidney functional reserve when they do actually develop CKD, and they are at higher risk for acute kidney injury.

  7. Capturing the age and spatial structures of migration

    NARCIS (Netherlands)

    Rogers, A; Raymer, J; Willekens, F

    2002-01-01

    In this paper we model the structures found in the level (generation) and allocation (distribution) components of age-specific and origin-destination-specific migration flows. For the examples, we examine the regional migration patterns in the USA for four periods: 1955-60, 1965-70, 1975-80, and 198

  8. Stable Solution of Nonlinear Age-structuredForest Evolution System

    Institute of Scientific and Technical Information of China (English)

    WANGDing-jiang; ZHAOTing-fang

    2004-01-01

    This paper studies the dynamical behavior of a class of total area dependent nonlinear age-structured forest evolution model. We give the problem of equal value for the forest system, and discuss the stable solution of system. We obtained the necessary and sufficient conditions for there exists the stable solution.

  9. Aging of the inceptive cellular population: the relationship between stem cells and aging.

    Science.gov (United States)

    Symonds, Catherine E; Galderisi, Umberto; Giordano, Antonio

    2009-04-02

    The average life expectancy worldwide has about doubled and the global population has increased six fold over the past century. With improving health care in the developed world there is a proportional augmentation in the treatment necessary for elderly patients occasioning the call for increased research in the area of aging and age-related diseases. The manifestation of this research has been focalized on the causative cellular processes and molecular mechanisms involved. Here we will discuss the efforts of this research in the area of stem cells, delving into the regulatory mechanisms and how their de-regulation could be attributed to aging and age-related diseases.

  10. The aged lymphoid tissue environment fails to support naïve T cell homeostasis.

    Science.gov (United States)

    Becklund, Bryan R; Purton, Jared F; Ramsey, Chris; Favre, Stéphanie; Vogt, Tobias K; Martin, Christopher E; Spasova, Darina S; Sarkisyan, Gor; LeRoy, Eric; Tan, Joyce T; Wahlus, Heidi; Bondi-Boyd, Brea; Luther, Sanjiv A; Surh, Charles D

    2016-01-01

    Aging is associated with a gradual loss of naïve T cells and a reciprocal increase in the proportion of memory T cells. While reduced thymic output is important, age-dependent changes in factors supporting naïve T cells homeostasis may also be involved. Indeed, we noted a dramatic decrease in the ability of aged mice to support survival and homeostatic proliferation of naïve T cells. The defect was not due to a reduction in IL-7 expression, but from a combination of changes in the secondary lymphoid environment that impaired naïve T cell entry and access to key survival factors. We observed an age-related shift in the expression of homing chemokines and structural deterioration of the stromal network in T cell zones. Treatment with IL-7/mAb complexes can restore naïve T cell homeostatic proliferation in aged mice. Our data suggests that homeostatic mechanisms that support the naïve T cell pool deteriorate with age.

  11. Age structure of the workforce and firm performance

    DEFF Research Database (Denmark)

    Westergård-Nielsen, Niels Chr.; Grund, Christian

    2008-01-01

    Purpose - Given the ongoing demographic change in European countries, this paper aims to exploreempirically the link between age structures of employees in firms and firm performance. Design/methodology/approach - Based on theoretical considerations, the paper examines the linkbetween both the av...... structures and firm performance for a whole country. The paper gives insights for both academic scholars and practitioners, who may take the results into account in formulating an efficient personnel policy.......Purpose - Given the ongoing demographic change in European countries, this paper aims to exploreempirically the link between age structures of employees in firms and firm performance. Design/methodology/approach - Based on theoretical considerations, the paper examines the linkbetween both...

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

    Science.gov (United States)

    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.

  13. Dynamic Scaling of Lipofuscin Deposition in Aging Cells

    Science.gov (United States)

    Family, Fereydoon; Mazzitello, K. I.; Arizmendi, C. M.; Grossniklaus, H. E.

    2011-07-01

    Lipofuscin is a membrane-bound cellular waste that can be neither degraded nor ejected from the cell but can only be diluted through cell division and subsequent growth. The fate of postmitotic (non-dividing) cells such as neurons, cardiac myocytes, skeletal muscle fibers, and retinal pigment epithelial cells (RPE) is to accumulate lipofuscin, which as an "aging pigment" has been considered a reliable biomarker for the age of cells. Environmental stress can accelerate the accumulation of lipofuscin. For example, accumulation in brain cells appears to be an important issue connected with heavy consumption of alcohol. Lipofuscin is made of free-radical-damaged protein and fat, whose abnormal accumulation is related to a range of disorders including Type IV mucolipidosis (ML4), Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease, Parkinson disease, and age-related macular degeneration (AMD) which is the leading cause of blindness beyond the age of 50 years. The study of lipofuscin formation and growth is important, because of their association with cellular aging. We introduce a model of non-equilibrium cluster growth and aggregation that we have developed for studying the formation and growth of lipofuscin. As an example of lipofuscin deposit in a given kind of postmitotic cell, we study the kinetics of lipofuscin growth in a RPE cell. Our results agree with a linear growth of the number of lipofuscin granules with age. We apply the dynamic scaling approach to our model and find excellent data collapse for the cluster size distribution. An unusual feature of our model is that while small particles are removed from the cell the larger ones become fixed and grow by aggregation.

  14. Traveling wave dispersal in partially sedentary age-structured populations

    CERN Document Server

    Le, Thuc Manh; Van Minh, Nguyen

    2010-01-01

    In this paper we present a thorough study on the existence of traveling waves in a mathematical model of dispersal in a partially sedentary age-structured population. This type of model was first proposed by Veit and Lewis in [{\\it Am. Nat.}, {\\bf 148} (1996), 255-274]. We choose the fecundity function to be the Beverton-Holt type function. We extend the theory of traveling waves in the population genetics model of Weinberger in [{\\it SIAM J. Math. Anal.}, {\\bf 13} (1982), 353-396] to the case when migration depends on age groups and a fraction of the population does not migrate.

  15. Canadian Provincial Population Growth: Fertility, Migration, and Age Structure Effects

    Directory of Open Access Journals (Sweden)

    Edmonston, Barry

    2009-01-01

    Full Text Available AbstractThe effect of changes in rates of mortality, fertility, and migration depend not only on the age specific patterns and levels of these rates, but on the age structure of the population. In orderto remove the influences of the age structure and concentrate on the impact of the demographic rates themselves, a common practice is to analyze the influences of the rates for a standard age structure. This paper adapts the general approach of using a standard age structure to a stationary population equivalent (SPE model, and analyzes current population change, using the SPE model, for provinces of Canada. Below-replacement fertility levels are only partially offset by net immigration. The SPE model evidences the decrease in the eventual provincial populations brought about by the below replacement fertility. Out-migration for some provincesto other areas of Canada accentuates their eventual population decreases.RésuméLes effets des changements des taux de mortalité, fécondité, et de migration dépendent non seulement des modèles par âge et des niveaux de ces taux, mais aussi de la structure par âge de la population. Pour éliminer les influences de la structure par âge et se concentrer sur les effets des taux démographiques mêmes, une pratique courante est d’analyser les influences des taux par une structure par âge de norme. Cet article adapte l’approche générale de la structure parâge à un modèle de population stationnaire équivalente (PSE. Cet article analyse les changements de population, en utilisant le modèle de PSE, dans les provinces canadiennes. Le taux de fécondité inférieur au seuil de reproduction de la population n’est que légèrement compensé par l’immigration nette. Le modèle de PSE démontre le déclin des populations provinciales éventuelles causé par le taux de fécondité inférieur au seuil de reproduction de la population. Le taux d’émigration entre certaines provinces et reste du

  16. Ageing management of french NPP civil work structures

    Science.gov (United States)

    Gallitre, E.; Dauffer, D.

    2011-04-01

    This paper presents EDF practice about concrete structure ageing management, from the mechanisms analysis to the formal procedure which allows the French company to increase 900 MWe NPP lifetime until 40 years; it will also introduce its action plan for 60 years lifetime extension. This practice is based on a methodology which identifies every ageing mechanism; both plants feedback and state of the art are screened and conclusions are drawn up into an "ageing analysis data sheet". That leads at first to a collection of 57 data sheets which give the mechanism identification, the components that are concerned and an analysis grid which is designed to assess the safety risk. This analysis screens the reference documents describing the mechanism, the design lifetime hypotheses, the associated regulation or codification, the feedback experiences, the accessibility, the maintenance actions, the repair possibility and so one. This analysis has to lead to a conclusion about the risk taking into account monitoring and maintenance. If the data sheet conclusion is not clear enough, then a more detailed report is launched. The technical document which is needed, is a formal detailed report which summarizes every theoretical knowledge and monitoring data: its objective is to propose a solution for ageing management: this solution can include more inspections or specific research development, or additional maintenance. After a first stage on the 900 MWe units, only two generic ageing management detailed reports have been needed for the civil engineering part: one about reactor building containment, and one about other structures which focuses on concrete inflating reactions. The second stage consists on deriving this generic analysis (ageing mechanism and detailed reports) to every plant where a complete ageing report is required (one report for all equipments and structures of the plant, but specific for each reactor). This ageing management is a continuous process because the

  17. Structure of cristae in cardiac mitochondria of aged rat

    OpenAIRE

    Riva, Alessandro; Tandler, Bernard; Lesnefsky, Edward J.; Conti, Gabriele; Loffredo, Felice; Vazquez, Edwin; Charles L Hoppel

    2006-01-01

    Interfibrillar mitochondria (IFM) of the heart in aged Fischer 344 rats show a biochemical defect which might be reflected in their morphology. We examined by high resolution scanning electron microscopy over 5,500 mitochondria to determine if a concomitant structural alteration existed. This methodology provides a means of examining mitochondrial cristae in three dimensions. Cristae of in situ subsarcolemmal mitochondria (SSM) and of IFM in both 6 and 24 month old Fischer rats are predominan...

  18. Age structure and disturbance legacy of North American forests

    Directory of Open Access Journals (Sweden)

    Y. Pan

    2011-03-01

    Full Text Available Most forests of the world are recovering from a past disturbance. It is well known that forest disturbances profoundly affect carbon stocks and fluxes in forest ecosystems, yet it has been a great challenge to assess disturbance impacts in estimates of forest carbon budgets. Net sequestration or loss of CO2 by forests after disturbance follows a predictable pattern with forest recovery. Forest age, which is related to time since disturbance, is a useful surrogate variable for analyses of the impact of disturbance on forest carbon. In this study, we compiled the first continental forest age map of North America by combining forest inventory data, historical fire data, optical satellite data and the dataset from NASA's Landsat Ecosystem Disturbance Adaptive Processing System (LEDAPS project. A companion map of the standard deviations for age estimates was developed for quantifying uncertainty. We discuss the significance of the disturbance legacy from the past, as represented by current forest age structure in different regions of the US and Canada, by analyzing the causes of disturbances from land management and nature over centuries and at various scales. We also show how such information can be used with inventory data for analyzing carbon management opportunities. By combining geographic information about forest age with estimated C dynamics by forest type, it is possible to conduct a simple but powerful analysis of the net CO2 uptake by forests, and the potential for increasing (or decreasing this rate as a result of direct human intervention in the disturbance/age status. Finally, we describe how the forest age data can be used in large-scale carbon modeling, both for land-based biogeochemistry models and atmosphere-based inversion models, in order to improve the spatial accuracy of carbon cycle simulations.

  19. Ultrasonographic assessment of skin structure according to age

    Directory of Open Access Journals (Sweden)

    Diana Crisan

    2012-01-01

    Full Text Available Background: High-frequency ultrasound is a noninvasive tool that offers characteristic markers, quantifying the cutaneous changes of the physiological senescence process. Aims: The aim was to assess the changes in skin thickness, dermal density and echogenicity, as part of the ageing process, with different age intervals. Methods : The study was performed on 160 patients, aged 40.4 ± 21.2, divided into four age categories: <20, 21-40, 41-60, 61-80. Ultrasonographic images (Dermascan device were taken from three sites: dorsal forearm (DF, medial arm (MA, zygomatic area (ZA. We assessed the thickness of epidermis and dermis (mm, number of low, medium, high echogenicity pixels, the ratio between the echogenicity of the upper and lower dermis (LEPs/LEPi, and SLEB (subepidermal low echogenicity band. The statistical analysis was performed using SPSS 15.00. A P value <0.05 was considered significant. Results: On all examined sites, it was found that the dermal thickness increases in the 21 to 40 year interval (P<0.0001. After the 21 to 40 year interval, the number of low echogenic pixels increases significantly, especially on photoexposed sites. High-echogenic pixels follow the same pattern on all examined sites: they increase in the 21 to 40 year interval and decrease in the 3rd and 4th age category. The LEPs/LEPi ratio increases significantly with age, at all sites (P<0.05, due to an increase of hypoechogenic pixels in the upper dermis. Conclusions: High-frequency ultrasound is a noninvasive "histological" tool that can assess the cutaneous structure and age-related changes. It offers imagistic markers, comparable to the histological parameters and also characteristic ultrasonographic markers. Histology remains the gold standard for the investigation of the integumentary system.

  20. Sox10 expressing cells in the lateral wall of the aged mouse and human cochlea.

    Directory of Open Access Journals (Sweden)

    Xinping Hao

    Full Text Available Age-related hearing loss (presbycusis is a common human disorder, affecting one in three Americans aged 60 and over. Previous studies have shown that presbyacusis is associated with a loss of non-sensory cells in the cochlear lateral wall. Sox10 is a transcription factor crucial to the development and maintenance of neural crest-derived cells including some non-sensory cell types in the cochlea. Mutations of the Sox10 gene are known to cause various combinations of hearing loss and pigmentation defects in humans. This study investigated the potential relationship between Sox10 gene expression and pathological changes in the cochlear lateral wall of aged CBA/CaJ mice and human temporal bones from older donors. Cochlear tissues prepared from young adult (1-3 month-old and aged (2-2.5 year-old mice, and human temporal bone donors were examined using quantitative immunohistochemical analysis and transmission electron microscopy. Cells expressing Sox10 were present in the stria vascularis, outer sulcus and spiral prominence in mouse and human cochleas. The Sox10(+ cell types included marginal and intermediate cells and outer sulcus cells, including those that border the scala media and those extending into root processes (root cells in the spiral ligament. Quantitative analysis of immunostaining revealed a significant decrease in the number of Sox10(+ marginal cells and outer sulcus cells in aged mice. Electron microscopic evaluation revealed degenerative alterations in the surviving Sox10(+ cells in aged mice. Strial marginal cells in human cochleas from donors aged 87 and older showed only weak immunostaining for Sox10. Decreases in Sox10 expression levels and a loss of Sox10(+ cells in both mouse and human aged ears suggests an important role of Sox10 in the maintenance of structural and functional integrity of the lateral wall. A loss of Sox10(+ cells may also be associated with a decline in the repair capabilities of non-sensory cells in the

  1. Age Structure of the Otter (Lutra lutra Population in England and Wales, and Problems with Cementum Ageing

    Directory of Open Access Journals (Sweden)

    Eleanor Sherrard-Smith

    2010-01-01

    Full Text Available Age is an important parameter in understanding population structure and age-dependent processes such as accumulation of contaminants. In the current study, canines and incisors of sub-adult and mature wild otters (Lutra lutra from England and Wales were sectioned and incremental cementum lines were used as an indication of age. The age structure of the sample population is much younger than some European populations (of 110 otters aged, only 10 were aged four or older. Cementum ageing is useful here in giving a broad indication of age structure, but is imprecise for species which do not exhibit seasonal breeding. Age is likely to be underestimated in most cases.

  2. DNA Damage Response in Hematopoietic Stem Cell Ageing

    Institute of Scientific and Technical Information of China (English)

    Tangliang Li; Zhong-Wei Zhou; Zhenyu Ju; Zhao-Qi Wang

    2016-01-01

    Maintenance of tissue-specific stem cells is vital for organ homeostasis and organismal longevity. Hematopoietic stem cells (HSCs) are the most primitive cell type in the hematopoietic system. They divide asymmetrically and give rise to daughter cells with HSC identity (self-renewal) and progenitor progenies (differentiation), which further proliferate and differentiate into full hematopoietic lineages. Mammalian ageing process is accompanied with abnormalities in the HSC self-renewal and differentiation. Transcriptional changes and epigenetic modulations have been implicated as the key regulators in HSC ageing process. The DNA damage response (DDR) in the cells involves an orchestrated signaling pathway, consisting of cell cycle regulation, cell death and senescence, transcriptional regulation, as well as chromatin remodeling. Recent studies employ-ing DNA repair-deficient mouse models indicate that DDR could intrinsically and extrinsically reg-ulate HSC maintenance and play important roles in tissue homeostasis of the hematopoietic system. In this review, we summarize the current understanding of how the DDR determines the HSC fates and finally contributes to organismal ageing.

  3. DNA Damage Response in Hematopoietic Stem Cell Ageing.

    Science.gov (United States)

    Li, Tangliang; Zhou, Zhong-Wei; Ju, Zhenyu; Wang, Zhao-Qi

    2016-06-01

    Maintenance of tissue-specific stem cells is vital for organ homeostasis and organismal longevity. Hematopoietic stem cells (HSCs) are the most primitive cell type in the hematopoietic system. They divide asymmetrically and give rise to daughter cells with HSC identity (self-renewal) and progenitor progenies (differentiation), which further proliferate and differentiate into full hematopoietic lineages. Mammalian ageing process is accompanied with abnormalities in the HSC self-renewal and differentiation. Transcriptional changes and epigenetic modulations have been implicated as the key regulators in HSC ageing process. The DNA damage response (DDR) in the cells involves an orchestrated signaling pathway, consisting of cell cycle regulation, cell death and senescence, transcriptional regulation, as well as chromatin remodeling. Recent studies employing DNA repair-deficient mouse models indicate that DDR could intrinsically and extrinsically regulate HSC maintenance and play important roles in tissue homeostasis of the hematopoietic system. In this review, we summarize the current understanding of how the DDR determines the HSC fates and finally contributes to organismal ageing.

  4. DNA Damage Response in Hematopoietic Stem Cell Ageing

    Directory of Open Access Journals (Sweden)

    Tangliang Li

    2016-06-01

    Full Text Available Maintenance of tissue-specific stem cells is vital for organ homeostasis and organismal longevity. Hematopoietic stem cells (HSCs are the most primitive cell type in the hematopoietic system. They divide asymmetrically and give rise to daughter cells with HSC identity (self-renewal and progenitor progenies (differentiation, which further proliferate and differentiate into full hematopoietic lineages. Mammalian ageing process is accompanied with abnormalities in the HSC self-renewal and differentiation. Transcriptional changes and epigenetic modulations have been implicated as the key regulators in HSC ageing process. The DNA damage response (DDR in the cells involves an orchestrated signaling pathway, consisting of cell cycle regulation, cell death and senescence, transcriptional regulation, as well as chromatin remodeling. Recent studies employing DNA repair-deficient mouse models indicate that DDR could intrinsically and extrinsically regulate HSC maintenance and play important roles in tissue homeostasis of the hematopoietic system. In this review, we summarize the current understanding of how the DDR determines the HSC fates and finally contributes to organismal ageing.

  5. Active sensors for health monitoring of aging aerospace structures

    Energy Technology Data Exchange (ETDEWEB)

    GIURGIUTIU,VICTOR; REDMOND,JAMES M.; ROACH,DENNIS P.; RACKOW,KIRK A.

    2000-02-29

    A project to develop non-intrusive active sensors that can be applied on existing aging aerospace structures for monitoring the onset and progress of structural damage (fatigue cracks and corrosion) is presented. The state of the art in active sensors structural health monitoring and damage detection is reviewed. Methods based on (a) elastic wave propagation and (b) electro-mechanical (E/M) impedance technique are cited and briefly discussed. The instrumentation of these specimens with piezoelectric active sensors is illustrated. The main detection strategies (E/M impedance for local area detection and wave propagation for wide area interrogation) are discussed. The signal processing and damage interpretation algorithms are tuned to the specific structural interrogation method used. In the high-frequency E/M impedance approach, pattern recognition methods are used to compare impedance signatures taken at various time intervals and to identify damage presence and progression from the change in these signatures. In the wave propagation approach, the acousto-ultrasonic methods identifying additional reflection generated from the damage site and changes in transmission velocity and phase are used. Both approaches benefit from the use of artificial intelligence neural networks algorithms that can extract damage features based on a learning process. Design and fabrication of a set of structural specimens representative of aging aerospace structures is presented. Three built-up specimens (pristine, with cracks, and with corrosion damage) are used. The specimen instrumentation with active sensors fabricated at the University of South Carolina is illustrated. Preliminary results obtained with the E/M impedance method on pristine and cracked specimens are presented.

  6. Cellular and molecular biology of aging endothelial cells.

    Science.gov (United States)

    Donato, Anthony J; Morgan, R Garrett; Walker, Ashley E; Lesniewski, Lisa A

    2015-12-01

    Cardiovascular disease (CVD) is the leading cause of death in the United States and aging is a major risk factor for CVD development. One of the major age-related arterial phenotypes thought to be responsible for the development of CVD in older adults is endothelial dysfunction. Endothelial function is modulated by traditional CVD risk factors in young adults, but advancing age is independently associated with the development of vascular endothelial dysfunction. This endothelial dysfunction results from a reduction in nitric oxide bioavailability downstream of endothelial oxidative stress and inflammation that can be further modulated by traditional CVD risk factors in older adults. Greater endothelial oxidative stress with aging is a result of augmented production from the intracellular enzymes NADPH oxidase and uncoupled eNOS, as well as from mitochondrial respiration in the absence of appropriate increases in antioxidant defenses as regulated by relevant transcription factors, such as FOXO. Interestingly, it appears that NFkB, a critical inflammatory transcription factor, is sensitive to this age-related endothelial redox change and its activation induces transcription of pro-inflammatory cytokines that can further suppress endothelial function, thus creating a vicious feed-forward cycle. This review will discuss the two macro-mechanistic processes, oxidative stress and inflammation, that contribute to endothelial dysfunction with advancing age as well as the cellular and molecular events that lead to the vicious cycle of inflammation and oxidative stress in the aged endothelium. Other potential mediators of this pro-inflammatory endothelial phenotype are increases in immune or senescent cells in the vasculature. Of note, genomic instability, telomere dysfunction or DNA damage has been shown to trigger cell senescence via the p53/p21 pathway and result in increased inflammatory signaling in arteries from older adults. This review will discuss the current state

  7. Aging characteristics of Li/SO(sub 2) cells

    Science.gov (United States)

    Levy, Samuel C.; Bouchard, Darryl A.

    Delays in the launch of the Galileo probe to Jupiter have resulted in a new trajectory that will increase the fly-out time such that batteries will be greater than seven years old at the time of descent into the Jovian atmosphere. The longest real time data for flight design cells was five years at the time of launch. A program was initiated to establish a methodology and data base so that the performance of these cells may be predicted at the time they are expected to complete the mission. Cells from five lots and five storage temperatures, ranging from one year to seven years in age, were studied. Chemical analysis was performed on one cell from each lot/storage group. The remaining cells in each group were discharged at the mission load and temperature. Additional cells were placed on high temperature accelerated storage, and then discharged.

  8. Precise age estimation from different ageing structures in the striped snakehead, Channa striata (Bloch,1793, collected from the river Ganga

    Directory of Open Access Journals (Sweden)

    Salman Khan

    2015-11-01

    Full Text Available In Channa striata (N=156; TL=17-60cm sampled from the river Ganga, the annuli laid on different ageing structures such as otoliths (whole and sectioned, scales, opercular bone and vertebrae were observed for age estimation. Standard procedures were followed to prepare and study the age structures. Age estimates obtained from different hard structures were analysed to calculate the parameters for precise age estimation viz., APE, CV and PA. The sectioned otoliths showed the highest (89.9% percentage of agreement between readers while least average percent error (1.20% and coefficient of variation (3.81% values between two readers. Thus sectioned otoliths were considered to be the most suitable method for estimating age in C. striata. When sectioned otoliths were compared with other bony structures, the highest percent agreement and lowest average percent error and coefficient of variation values were found between sectioned otoliths and whole otoliths age estimates.

  9. Structure and functions of fungal cell surfaces

    Science.gov (United States)

    Nozawa, Y.

    1984-01-01

    A review with 24 references on the biochemistry, molecular structure, and function of cell surfaces of fungi, especially dermatophytes: the chemistry and structure of the cell wall, the effect of polyene antibiotics on the morphology and function of cytoplasmic membranes, and the chemical structure and function of pigments produced by various fungi are discussed.

  10. Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice

    NARCIS (Netherlands)

    Chang, Jianhui; Wang, Yingying; Shao, Lijian; Laberge, Remi-Martin; Demaria, Marco; Campisi, Judith; Janakiraman, Krishnamurthy; Sharpless, Norman E; Ding, Sheng; Feng, Wei; Luo, Yi; Wang, Xiaoyan; Aykin-Burns, Nukhet; Krager, Kimberly; Ponnappan, Usha; Hauer-Jensen, Martin; Meng, Aimin; Zhou, Daohong

    2015-01-01

    Senescent cells (SCs) accumulate with age and after genotoxic stress, such as total-body irradiation (TBI). Clearance of SCs in a progeroid mouse model using a transgenic approach delays several age-associated disorders, suggesting that SCs play a causative role in certain age-related pathologies. T

  11. Polycomb group proteins in hematopoietic stem cell aging and malignancies

    NARCIS (Netherlands)

    Klauke, Karin; de Haan, Gerald

    2011-01-01

    Protection of the transcriptional "stemness" network is important to maintain a healthy hematopoietic stem cells (HSCs) compartment during the lifetime of the organism. Recent evidence shows that fundamental changes in the epigenetic status of HSCs might be one of the driving forces behind many age-

  12. Programmed cell death of Ulmus pumila L. seeds during aging

    Institute of Scientific and Technical Information of China (English)

    Yulan ZHANG; Ming ZHANG; Fang LI; Xiaofeng WANG

    2008-01-01

    The programmed cell death (PCD) character-istics of Ulmus pumila L. seeds were investigated. The seeds were treated at a high temperature of 37℃ and 100% relative humidity for six days. DAPI (4'6-diami-dino-2-phenylindole) staining revealed that the aging treatment induced condensation and margination of chro-matin, as well as the formation of apoptotic bodies. DNA electrophoresis results of U. pumila seeds on an agarose gel showed a characteristic "ladder" pattern. Levels of electrolyte leakage of seed cells showed that membranes retained their integral form during almost the entire aging time. There was an immediate increase in the production rate of superoxide anion (O2-) and in the amount of hydrogen peroxide (H2O2), which remained at a μmol level. All of these common characteristics indicate that seed aging can be classified as PCD.

  13. Polycomb group proteins in hematopoietic stem cell aging and malignancies.

    Science.gov (United States)

    Klauke, Karin; de Haan, Gerald

    2011-07-01

    Protection of the transcriptional "stemness" network is important to maintain a healthy hematopoietic stem cells (HSCs) compartment during the lifetime of the organism. Recent evidence shows that fundamental changes in the epigenetic status of HSCs might be one of the driving forces behind many age-related HSC changes and might pave the way for HSC malignant transformation and subsequent leukemia development, the incidence of which increases exponentially with age. Polycomb group (PcG) proteins are key epigenetic regulators of HSC cellular fate decisions and are often found to be misregulated in human hematopoietic malignancies. In this review, we speculate that PcG proteins balance HSC aging against the risk of developing cancer, since a disturbance in PcG genes and proteins affects several important cellular processes such as cell fate decisions, senescence, apoptosis, and DNA damage repair.

  14. Biology 23. Unit One -- The Cell: Structure and Physiology.

    Science.gov (United States)

    Nederland Independent School District, TX.

    GRADES OR AGES: Not given. SUBJECT MATTER: Biology, the structure and physiology of the cell. ORGANIZATION AND PHYSICAL APPEARANCE: There are four sections: a) objectives for the unit, b) bibliography, c) activities, and d) evaluation. The guide is directed to the student rather than the teacher. The guide is mimeographed and stapled, with no…

  15. Age structure and disturbance legacy of North American forests

    Directory of Open Access Journals (Sweden)

    Y. Pan

    2010-02-01

    Full Text Available Most forests of the world are recovering from a past disturbance. It is well known that forest disturbances profoundly affect carbon stock and fluxes in forest ecosystems, yet it has been a great challenge to assess disturbance impacts in estimates of forest carbon budgets. Net sequestration or loss of CO2 by forests after disturbance follows a predictable pattern with forest recovery. Forest age, which is related to time since disturbance, is the most available surrogate variable for various forest carbon analyses that concern the impact of disturbance. In this study, we compiled the first continental forest age map of North America by combining forest inventory data, historical fire data, optical satellite data and the dataset from NASA's LEDAPS project. Mexico and interior Alaska are excluded from this initial map due to unavailability of all required data sets, but work is underway to develop some different methodology for these areas. We discuss the significance of disturbance legacy from the past, as represented by current forest age structure in different regions of the US and Canada, tracking back disturbances caused by human and nature over centuries and at various scales. We also show how such information can be used with inventory data for analyzing carbon management opportunities, and other modeling applications. By combining geographic information about forest age with estimated C dynamics by forest type, it is possible to conduct a simple but powerful analysis of the net CO2 uptake by forests, and the potential for increasing (or decreasing this rate as a result of direct human intervention in the disturbance/age status. The forest age map may also help address the recent concern that the terrestrial C sink from forest regrowth in North America may saturate in the next few decades. Finally, we describe how the forest age data can be used in large-scale carbon modeling, both for land-based biogeochemistry

  16. Microglial cell dysregulation in Brain Aging and Neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Rommy eVon Bernhardi

    2015-07-01

    Full Text Available Aging is the main risk factor for neurodegenerative diseases. In aging, microglia undergo phenotypic changes compatible with their activation. Glial activation can lead to neuroinflammation, which is increasingly accepted as part of the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD. We hypothesize that in aging, aberrant microglia activation leads to a deleterious environment and neurodegeneration. In aged mice, microglia exhibit an increased expression of cytokines and an exacerbated inflammatory response to pathological changes. Whereas LPS increases nitric oxide secretion in microglia from young mice, induction of reactive oxygen species (ROS predominates in older mice. Furthermore, there is accumulation of DNA oxidative damage in mitochondria of microglia during aging, and also an increased intracellular ROS production. Increased ROS activates the redox-sensitive nuclear factor kappa B, which promotes more neuroinflammation, and can be translated in functional deficits, such as cognitive impairment. Mitochondria-derived ROS and cathepsin B, are also necessary for the microglial cell production of interleukin-1β, a key inflammatory cytokine. Interestingly, whereas the regulatory cytokine TGFβ1 is also increased in the aged brain, neuroinflammation persists. Assessing this apparent contradiction, we have reported that TGFβ1 induction and activation of Smad3 signaling after inflammatory stimulation are reduced in adult mice. Other protective functions, such as phagocytosis, although observed in aged animals, become not inducible by inflammatory stimuli and TGFβ1. Here, we discuss data suggesting that mitochondrial and endolysosomal dysfunction could at least partially mediate age-associated microglial cell changes, and, together with the impairment of the TGFβ1-Smad3 pathway, could result in a reduction of protective activation and a facilitation of cytotoxic activation of microglia, resulting in the

  17. Kinetic theory of age-structured stochastic birth-death processes

    Science.gov (United States)

    Greenman, Chris D.; Chou, Tom

    2016-01-01

    Classical age-structured mass-action models such as the McKendrick-von Foerster equation have been extensively studied but are unable to describe stochastic fluctuations or population-size-dependent birth and death rates. Stochastic theories that treat semi-Markov age-dependent processes using, e.g., the Bellman-Harris equation do not resolve a population's age structure and are unable to quantify population-size dependencies. Conversely, current theories that include size-dependent population dynamics (e.g., mathematical models that include carrying capacity such as the logistic equation) cannot be easily extended to take into account age-dependent birth and death rates. In this paper, we present a systematic derivation of a new, fully stochastic kinetic theory for interacting age-structured populations. By defining multiparticle probability density functions, we derive a hierarchy of kinetic equations for the stochastic evolution of an aging population undergoing birth and death. We show that the fully stochastic age-dependent birth-death process precludes factorization of the corresponding probability densities, which then must be solved by using a Bogoliubov--Born--Green--Kirkwood--Yvon-like hierarchy. Explicit solutions are derived in three limits: no birth, no death, and steady state. These are then compared with their corresponding mean-field results. Our results generalize both deterministic models and existing master equation approaches by providing an intuitive and efficient way to simultaneously model age- and population-dependent stochastic dynamics applicable to the study of demography, stem cell dynamics, and disease evolution.

  18. Impact of structural aging on seismic risk assessment of reinforced concrete structures in nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Ellingwood, B.; Song, J. [Johns Hopkins Univ., Baltimore, MD (United States). Dept. of Civil Engineering

    1996-03-01

    The Structural Aging Program is addressing the potential for degradation of concrete structural components and systems in nuclear power plants over time due to aging and aggressive environmental stressors. Structures are passive under normal operating conditions but play a key role in mitigating design-basis events, particularly those arising from external challenges such as earthquakes, extreme winds, fires and floods. Structures are plant-specific and unique, often are difficult to inspect, and are virtually impossible to replace. The importance of structural failures in accident mitigation is amplified because such failures may lead to common-cause failures of other components. Structural condition assessment and service life prediction must focus on a few critical components and systems within the plant. Components and systems that are dominant contributors to risk and that require particular attention can be identified through the mathematical formalism of a probabilistic risk assessment, or PRA. To illustrate, the role of structural degradation due to aging on plant risk is examined through the framework of a Level 1 seismic PRA of a nuclear power plant. Plausible mechanisms of structural degradation are found to increase the core damage probability by approximately a factor of two.

  19. Loss of CD34 expression in aging human choriocapillaris endothelial cells.

    Directory of Open Access Journals (Sweden)

    Elliott H Sohn

    Full Text Available Structural and gene expression changes in the microvasculature of the human choroid occur during normal aging and age-related macular degeneration (AMD. In this study, we sought to determine the impact of aging and AMD on expression of the endothelial cell glycoprotein CD34. Sections from 58 human donor eyes were categorized as either young (under age 40, age-matched controls (> age 60 without AMD, or AMD affected (>age 60 with early AMD, geographic atrophy, or choroidal neovascularization. Dual labeling of sections with Ulex europaeus agglutinin-I lectin (UEA-I and CD34 antibodies was performed, and the percentage of capillaries labeled with UEA-I but negative for anti-CD34 was determined. In addition, published databases of mouse and human retinal pigment epithelium-choroid were evaluated and CD34 expression compared between young and old eyes. Immunohistochemical studies revealed that while CD34 and UEA-I were colocalized in young eyes, there was variable loss of CD34 immunoreactivity in older donor eyes. While differences between normal aging and AMD were not significant, the percentage of CD34 negative capillaries in old eyes, compared to young eyes, was highly significant (p = 3.8×10(-6. Endothelial cells in neovascular membranes were invariably CD34 positive. Published databases show either a significant decrease in Cd34 (mouse or a trend toward decreased CD34 (human in aging. These findings suggest that UEA-I and endogenous alkaline phosphatase activity are more consistent markers of aging endothelial cells in the choroid, and suggest a possible mechanism for the increased inflammatory milieu in the aging choroid.

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

    Science.gov (United States)

    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.

  1. Effects of Reference Performance Testing During Aging Using Commercial Cells

    Energy Technology Data Exchange (ETDEWEB)

    Jon P. Christophersen; Chinh D. Ho; David Howell

    2005-07-01

    The Advanced Technology Development Program, under the oversight of the U.S. Department of Energy’s FreedomCAR and Vehicle Technologies Program, is investigating lithium-ion batteries for hybrid-electric vehicle applications. Cells are aged under various test conditions, including temperatures and states-of-charge. Life testing is interrupted at regular intervals to conduct reference performance tests (RPTs), which are used to measure changes in the electrical performance of the cells and then to determine cell degradation as a function of test time. Although designed to be unobtrusive, data from the Advanced Technology Development Gen 2 cells indicated that RPTs actually contributed to cell degradation and failure. A study was performed at the Idaho National Laboratory using commercially available lithium-ion cells to determine the impact of RPTs on life. A series of partial RPTs were performed at regular intervals during life testing and compared to a control group that was life tested without RPT interruption. It was determined that certain components of the RPT were detrimental, while others appeared to improve cell performance. Consequently, a new "mini" RPT was designed as an unobtrusive alternative. Initial testing with commercial cells indicates that the impact of the mini RPT is significantly less than the Gen 2 cell RPT.

  2. Systemic Problems: A perspective on stem cell aging and rejuvenation

    Science.gov (United States)

    Conboy, Irina M.; Conboy, Michael J.; Rebo, Justin

    2015-01-01

    This review provides balanced analysis of the advances in systemic regulation of young and old tissue stem cells and suggests strategies for accelerating development of therapies to broadly combat age-related tissue degenerative pathologies. Many highlighted recent reports on systemic tissue rejuvenation combine parabiosis with a “silver bullet” putatively responsible for the positive effects. Attempts to unify these papers reflect the excitement about this experimental approach and add value in reproducing previous work. At the same time, defined molecular approaches, which are “beyond parabiosis” for the rejuvenation of multiple old organs represent progress toward attenuating or even reversing human tissue aging. PMID:26540176

  3. Changes in intracellular calcium in brain cells of aged rats

    Institute of Scientific and Technical Information of China (English)

    Yu Li; Yunpeng Cao

    2008-01-01

    BACKGROUND: Studies have shown that voltage-dependent calcium influx, and enhancement of certain calcium-dependent processes in neurons, is related to aging. OBJECTIVE: To observe changes in intracellular calcium ([Ca2+]i) in neurons of aged rats, and to compare with young rats. DESIGN, TIME AND SETTING: A randomized control experiment of neurophysiology was performed at the Central Laboratory of School of Pharmaceutical Science, China Medical University from June to August 2004. MATERIALS: Ten male, healthy, Wistar rats, 19 months old, were selected for the aged group. Ten male, 3-month-old, Wistar rats were selected for the young control group. Fura-2/AM was provided by the Institute of Pharmaceutical Research of Chinese Academy of Medical Sciences, and the F-2000 fluorospectrophotometer was a product of Hitachi, Japan. METHODS: Fluorescence Fura-2 spectrophotometer was used to measure [Ca2+]i in acutely dissociated brain cells of aged and young rats. The concentration of extracellular potassium was controlled by adding different volumes of chloridated potassium solution of high concentration. MAIN OUTCOME MEASURES: [Ca2+]i in neurons of young and aged rats in the presence of 1 mmol/L extracellular calcium concentration and 0 mmol/L (resting state), 5, 10, 20, and 40 mmol/L extracellular potassium. Absolute increase of [Ca2+]i in neurons of young and aged rats when extraceUular potassium was 5,10,20, 40 mmol/L. RESULTS: In the presence of 1 mmol/L extracellular Ca2+ and 0 mmol/L (resting state), 5, 10, 20, and 40 mmol/L extracellular potassium, [Ca2+]i in the neurons of aged rats was significantly less than that in young rats (P 0.05). CONCLUSION: The overload of [Ca2+]i in neurons of aged rats is greater than that of young rats under the same circumstances.

  4. Age-related changes of structures in cerebellar cortex of cat

    Indian Academy of Sciences (India)

    Changzheng Zhang; Tianmiao Hua; Zaiman Zhu; Xun Luo

    2006-03-01

    We studied the structures of the cerebellar cortex of young adult and old cats for age-related changes, which were statistically analysed. Nissl staining was used to visualize the cortical neurons. The immunohistochemical method was used to display glial fibrillary acidic protein (GFAP)-immunoreactive (IR) astrocytes and neurofilament-immunoreactive (NF-IR) neurons. Under the microscope, the thickness of the cerebellar cortex was measured; and the density of neurons in all the layers as well as that of GFAP-IR cells in the granular layer was analysed. Compared with young adult cats, the thickness of the molecular layer and total cerebellar cortex was significantly decreased in old cats, and that of the granular layer increased. The density of neurons in each layer was significantly lower in old cats than in young adult ones. Astrocytes in old cats were significantly denser than in young adult ones, and accompanied by evident hypertrophy of the cell bodies and enhanced immunoreaction of GFAP substance. Purkinje cells (PCs) in old cats showed much fewer NF-IR dendrites than those in young adults. The above findings indicate a loss of neurons and decrease in the number of dendrites of the PCs in the aged cerebellar cortex, which might underlie the functional decline of afferent efficacy and information integration in the senescent cerebellum. An age-dependent enhancement of activity of the astrocytes may exert a protective effect on neurons in the aged cerebellum.

  5. Acrylamide induces accelerated endothelial aging in a human cell model.

    Science.gov (United States)

    Sellier, Cyril; Boulanger, Eric; Maladry, François; Tessier, Frédéric J; Lorenzi, Rodrigo; Nevière, Rémi; Desreumaux, Pierre; Beuscart, Jean-Baptiste; Puisieux, François; Grossin, Nicolas

    2015-09-01

    Acrylamide (AAM) has been recently discovered in food as a Maillard reaction product. AAM and glycidamide (GA), its metabolite, have been described as probably carcinogenic to humans. It is widely established that senescence and carcinogenicity are closely related. In vitro, endothelial aging is characterized by replicative senescence in which primary cells in culture lose their ability to divide. Our objective was to assess the effects of AAM and GA on human endothelial cell senescence. Human umbilical vein endothelial cells (HUVECs) cultured in vitro were used as model. HUVECs were cultured over 3 months with AAM or GA (1, 10 or 100 μM) until growth arrest. To analyze senescence, β-galactosidase activity and telomere length of HUVECs were measured by cytometry and semi-quantitative PCR, respectively. At all tested concentrations, AAM or GA reduced cell population doubling compared to the control condition (p < 0.001). β-galactosidase activity in endothelial cells was increased when exposed to AAM (≥10 μM) or GA (≥1 μM) (p < 0.05). AAM (≥10 μM) or GA (100 μM) accelerated telomere shortening in HUVECs (p < 0.05). In conclusion, in vitro chronic exposure to AAM or GA at low concentrations induces accelerated senescence. This result suggests that an exposure to AAM might contribute to endothelial aging.

  6. Regenerative Potential of Mesenchymal Stromal Cells: Age-Related Changes

    Science.gov (United States)

    Bruna, Flavia; Contador, David; Conget, Paulette; Erranz, Benjamín; Sossa, Claudia L.; Arango-Rodríguez, Martha L.

    2016-01-01

    Preclinical and clinical studies have shown that a therapeutic effect results from mesenchymal stromal cells (MSCs) transplant. No systematic information is currently available regarding whether donor age modifies MSC regenerative potential on cutaneous wound healing. Here, we evaluate whether donor age influences this potential. Two different doses of bone marrow MSCs (BM-MSCs) from young, adult, or old mouse donors or two doses of their acellular derivatives mesenchymal stromal cells (acd-MSCs) were intradermally injected around wounds in the midline of C57BL/6 mice. Every two days, wound healing was macroscopically assessed (wound closure) and microscopically assessed (reepithelialization, dermal-epidermal junction, skin appendage regeneration, granulation tissue, leukocyte infiltration, and density dermal collagen fibers) after 12 days from MSC transplant. Significant differences in the wound closure kinetic, quality, and healing of skin regenerated were observed in lesions which received BM-MSCs from different ages or their acd-MSCs compared to lesions which received vehicle. Nevertheless, our data shows that adult's BM-MSCs or their acd-MSCs were the most efficient for recovery of most parameters analyzed. Our data suggest that MSC efficacy was negatively affected by donor age, where the treatment with adult's BM-MSCs or their acd-MSCs in cutaneous wound promotes a better tissue repair/regeneration. This is due to their paracrine factors secretion. PMID:27247575

  7. Age-related reduction of structural complexity in spleen hematopoietic tissue architecture in mice.

    Science.gov (United States)

    Pantic, Igor; Paunovic, Jovana; Basta-Jovanovic, Gordana; Perovic, Milan; Pantic, Senka; Milosevic, Nebojsa T

    2013-09-01

    The effects of aging on structural complexity in hematopoietic tissue are unknown. In this work, in a mouse experimental model, we report the age-related reduction of spleen hematopoietic tissue (SHT) complexity. Spleen tissue was obtained from the total of 64 male Swiss albino mice divided into 8 age groups: newborns (0 days old), 10 days, 20 days, 30 days, 120 days, 210 days, 300 and 390 days old. SHT was stained using conventional hematoxylin/eosin, and DNA-binding toluidine blue dyes. Fractal dimension as an indicator of cellular complexity, and lacunarity as indicator of tissue heterogeneity were determined based on the binarized SHT micrographs. Results indicate that fractal dimension of mice spleen hematopoietic tissue decreases with age, while lacunarity increases. These changes/trends have been detected in SHT stained both with toluidine blue and conventional hematoxylin/eosin. Fractal dimension was negatively correlated with lacunarity. The detected reduction in complexity suggests that age-related structural changes are present in mouse SHT both in general tissue architecture and progenitor cell DNA.

  8. Age structure of elephants in Liwonde National Park, Malawi

    Directory of Open Access Journals (Sweden)

    R. Bhima

    1997-02-01

    Full Text Available The age structure of the elephant population in Liwonde National Park, Malawi was determined for the first time in 1993 and again in 1995 using the photogrammetric method. Sampling was done during a four year-long severe drought from 1991/92 to 1994/95. The drought reached its highest intensity in the first year. Therefore, the study also attempted to assess the impact of the drought on the population. The results show that the population consisted of mostly young animals <5 years old (52.6 and 44.8 in 1993 and 1995, respectively. The other age cohorts were as follows: 6-10 years old - 16.1 and 21.7 ; 11-15 years old - 7.8 and 9.2 ; 16-20 years old - 5.2 and 4.7 ; and >20 years old - 18.3 and 20.5 . The population is young and growing. The prolonged drought did not have any significant impact on the population.

  9. 77 FR 27815 - Aging Management of Stainless Steel Structures and Components in Treated Borated Water

    Science.gov (United States)

    2012-05-11

    ... COMMISSION Aging Management of Stainless Steel Structures and Components in Treated Borated Water AGENCY..., ``Aging Management of Stainless Steel Structures and Components in Treated Borated Water.'' This LR-ISG... Power Plants (SRP-LR) and Generic Aging Lessons Learned (GALL) Report for the aging management...

  10. Decreased Laminin Expression by Human Lung Epithelial Cells and Fibroblasts Cultured in Acellular Lung Scaffolds from Aged Mice.

    Science.gov (United States)

    Godin, Lindsay M; Sandri, Brian J; Wagner, Darcy E; Meyer, Carolyn M; Price, Andrew P; Akinnola, Ifeolu; Weiss, Daniel J; Panoskaltsis-Mortari, Angela

    2016-01-01

    The lung changes functionally and structurally with aging. However, age-related effects on the extracellular matrix (ECM) and corresponding effects on lung cell behavior are not well understood. We hypothesized that ECM from aged animals would induce aging-related phenotypic changes in healthy inoculated cells. Decellularized whole organ scaffolds provide a powerful model for examining how ECM cues affect cell phenotype. The effects of age on ECM composition in both native and decellularized mouse lungs were assessed as was the effect of young vs old acellular ECM on human bronchial epithelial cells (hBECs) and lung fibroblasts (hLFs). Native aged (1 year) lungs demonstrated decreased expression of laminins α3 and α4, elastin and fibronectin, and elevated collagen, compared to young (3 week) lungs. Proteomic analyses of decellularized ECM demonstrated similar findings, and decellularized aged lung ECM contained less diversity in structural proteins compared to young ECM. When seeded in old ECM, hBECs and hLFs demonstrated lower gene expression of laminins α3 and α4, respectively, as compared to young ECM, paralleling the laminin deficiency of aged ECM. ECM changes appear to be important factors in potentiating aging-related phenotypes and may provide clues to mechanisms that allow for aging-related lung diseases.

  11. Decreased Laminin Expression by Human Lung Epithelial Cells and Fibroblasts Cultured in Acellular Lung Scaffolds from Aged Mice.

    Directory of Open Access Journals (Sweden)

    Lindsay M Godin

    Full Text Available The lung changes functionally and structurally with aging. However, age-related effects on the extracellular matrix (ECM and corresponding effects on lung cell behavior are not well understood. We hypothesized that ECM from aged animals would induce aging-related phenotypic changes in healthy inoculated cells. Decellularized whole organ scaffolds provide a powerful model for examining how ECM cues affect cell phenotype. The effects of age on ECM composition in both native and decellularized mouse lungs were assessed as was the effect of young vs old acellular ECM on human bronchial epithelial cells (hBECs and lung fibroblasts (hLFs. Native aged (1 year lungs demonstrated decreased expression of laminins α3 and α4, elastin and fibronectin, and elevated collagen, compared to young (3 week lungs. Proteomic analyses of decellularized ECM demonstrated similar findings, and decellularized aged lung ECM contained less diversity in structural proteins compared to young ECM. When seeded in old ECM, hBECs and hLFs demonstrated lower gene expression of laminins α3 and α4, respectively, as compared to young ECM, paralleling the laminin deficiency of aged ECM. ECM changes appear to be important factors in potentiating aging-related phenotypes and may provide clues to mechanisms that allow for aging-related lung diseases.

  12. Type I collagen aging impairs discoidin domain receptor 2-mediated tumor cell growth suppression.

    Science.gov (United States)

    Saby, Charles; Buache, Emilie; Brassart-Pasco, Sylvie; El Btaouri, Hassan; Courageot, Marie-Pierre; Van Gulick, Laurence; Garnotel, Roselyne; Jeannesson, Pierre; Morjani, Hamid

    2016-05-03

    Tumor cells are confronted to a type I collagen rich environment which regulates cell proliferation and invasion. Biological aging has been associated with structural changes of type I collagen. Here, we address the effect of collagen aging on cell proliferation in a three-dimensional context (3D).We provide evidence for an inhibitory effect of adult collagen, but not of the old one, on proliferation of human fibrosarcoma HT-1080 cells. This effect involves both the activation of the tyrosine kinase Discoidin Domain Receptor 2 (DDR2) and the tyrosine phosphatase SHP-2. DDR2 and SHP-2 were less activated in old collagen. DDR2 inhibition decreased SHP-2 phosphorylation in adult collagen and increased cell proliferation to a level similar to that observed in old collagen.In the presence of old collagen, a high level of JAK2 and ERK1/2 phosphorylation was observed while expression of the cell cycle negative regulator p21CIP1 was decreased. Inhibition of DDR2 kinase function also led to an increase in ERK1/2 phosphorylation and a decrease in p21CIP1 expression. Similar signaling profile was observed when DDR2 was inhibited in adult collagen. Altogether, these data suggest that biological collagen aging could increase tumor cell proliferation by reducingthe activation of the key matrix sensor DDR2.

  13. Bone marrow mesenchymal stem cells protect against retinal ganglion cell loss in aged rats with glaucoma

    Directory of Open Access Journals (Sweden)

    Hu Y

    2013-10-01

    Full Text Available Ying Hu,1,2 Hai Bo Tan,1 Xin Mei Wang,3 Hua Rong,1 Hong Ping Cui,1 Hao Cui2 Departments of Ophthalmology, 1Shanghai East Hospital of Tongji University, Shanghai, 2First Affiliated Hospital, 3Fourth Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China Abstract: Glaucoma is a common eye disease in the aged population and has severe consequences. The present study examined the therapeutic effects of bone marrow mesenchymal stem cell (BMSC transplantation in preventing loss of visual function in aged rats with glaucoma caused by laser-induced ocular hypertension. We found that BMSCs promoted survival of retinal ganglion cells in the transplanted eye as compared with the control eye. Further, in swimming tests guided by visual cues, the rats with a BMSC transplant performed significantly better. We believe that BMSC transplantation therapy is effective in treating aged rats with glaucoma. Keywords: glaucoma, stem cell, transplantation, cell therapy, aging

  14. Single-cell RNA sequencing reveals molecular and functional platelet bias of aged haematopoietic stem cells.

    Science.gov (United States)

    Grover, Amit; Sanjuan-Pla, Alejandra; Thongjuea, Supat; Carrelha, Joana; Giustacchini, Alice; Gambardella, Adriana; Macaulay, Iain; Mancini, Elena; Luis, Tiago C; Mead, Adam; Jacobsen, Sten Eirik W; Nerlov, Claus

    2016-03-24

    Aged haematopoietic stem cells (HSCs) generate more myeloid cells and fewer lymphoid cells compared with young HSCs, contributing to decreased adaptive immunity in aged individuals. However, it is not known how intrinsic changes to HSCs and shifts in the balance between biased HSC subsets each contribute to the altered lineage output. Here, by analysing HSC transcriptomes and HSC function at the single-cell level, we identify increased molecular platelet priming and functional platelet bias as the predominant age-dependent change to HSCs, including a significant increase in a previously unrecognized class of HSCs that exclusively produce platelets. Depletion of HSC platelet programming through loss of the FOG-1 transcription factor is accompanied by increased lymphoid output. Therefore, increased platelet bias may contribute to the age-associated decrease in lymphopoiesis.

  15. Epigenetic dysregulation in mesenchymal stem cell aging and spontaneous differentiation.

    Directory of Open Access Journals (Sweden)

    Zhilong Li

    Full Text Available BACKGROUND: Mesenchymal stem cells (MSCs hold great promise for the treatment of difficult diseases. As MSCs represent a rare cell population, ex vivo expansion of MSCs is indispensable to obtain sufficient amounts of cells for therapies and tissue engineering. However, spontaneous differentiation and aging of MSCs occur during expansion and the molecular mechanisms involved have been poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Human MSCs in early and late passages were examined for their expression of genes involved in osteogenesis to determine their spontaneous differentiation towards osteoblasts in vitro, and of genes involved in self-renewal and proliferation for multipotent differentiation potential. In parallel, promoter DNA methylation and hostone H3 acetylation levels were determined. We found that MSCs underwent aging and spontaneous osteogenic differentiation upon regular culture expansion, with progressive downregulation of TERT and upregulation of osteogenic genes such as Runx2 and ALP. Meanwhile, the expression of genes associated with stem cell self-renewal such as Oct4 and Sox2 declined markedly. Notably, the altered expression of these genes were closely associated with epigenetic dysregulation of histone H3 acetylation in K9 and K14, but not with methylation of CpG islands in the promoter regions of most of these genes. bFGF promoted MSC proliferation and suppressed its spontaneous osteogenic differentiation, with corresponding changes in histone H3 acetylation in TERT, Oct4, Sox2, Runx2 and ALP genes. CONCLUSIONS/SIGNIFICANCE: Our results indicate that histone H3 acetylation, which can be modulated by extrinsic signals, plays a key role in regulating MSC aging and differentiation.

  16. Mechanistic insights into aging, cell cycle progression, and stress response

    Directory of Open Access Journals (Sweden)

    Troy Anthony Alan Harkness

    2012-06-01

    Full Text Available The longevity of an organism depends on the health of its cells. Throughout life cells are exposed to numerous intrinsic and extrinsic stresses, such as free radicals, generated through mitochondrial electron transport, and ultraviolet irradiation. The cell has evolved numerous mechanisms to scavenge free radicals and repair damage induced by these insults. One mechanism employed by the yeast Saccharomyces cerevisiae to combat stress utilizes the Anaphase Promoting Complex (APC, an essential multi-subunit ubiquitin-protein ligase structurally and functionally conserved from yeast to humans that controls progression through mitosis and G1. We have observed that yeast cells expressing compromised APC subunits are sensitive to multiple stresses and have shorter replicative and chronological lifespans. In a pathway that runs parallel to that regulated by the APC, members of the Forkhead box (Fox transcription factor family also regulate stress responses. The yeast Fox orthologues Fkh1 and Fkh2 appear to drive the transcription of stress response factors and slow early G1 progression, while the APC seems to regulate chromatin structure, chromosome segregation, and resetting of the transcriptome in early G1. In contrast, under non-stress conditions, the Fkhs play a complex role in cell cycle progression, partially through activation of the APC. Direct and indirect interactions between the APC and the yeast Fkhs appear to be pivotal for lifespan determination. Here we explore the potential for these interactions to be evolutionarily conserved as a mechanism to balance cell cycle regulation with stress responses.

  17. THE STRUCTURE ANALYSIS OF POPULATION BY AGE GROUPS IN THE RURAL AREAS OF BUCOVINA

    Directory of Open Access Journals (Sweden)

    NICOLETA ILEANA MORAR (BUMBU

    2015-12-01

    Full Text Available The structure analysis of population by age groups in the rural area of Bucovina desires to create a recent image of the rural population by age groups in the region of Bucovina , provided that after the year 2000 have occurred socio – economic changes with repercussions on the demographic component. The structure analysis by age group will be based on the share of population indicators on the major age groups, the share of population by age and quinquennial gender illustrated by age pyramid, the index of demographic aging and age-dependency ratio. This study is definitely needed in forecasting future regional development objectives and measures.

  18. Cell Secretion: Current Structural and Biochemical Insights

    Directory of Open Access Journals (Sweden)

    Saurabh Trikha

    2010-01-01

    Full Text Available Essential physiological functions in eukaryotic cells, such as release of hormones and digestive enzymes, neurotransmission, and intercellular signaling, are all achieved by cell secretion. In regulated (calcium-dependent secretion, membrane-bound secretory vesicles dock and transiently fuse with specialized, permanent, plasma membrane structures, called porosomes or fusion pores. Porosomes are supramolecular, cup-shaped lipoprotein structures at the cell plasma membrane that mediate and control the release of vesicle cargo to the outside of the cell. The sizes of porosomes range from 150nm in diameter in acinar cells of the exocrine pancreas to 12nm in neurons. In recent years, significant progress has been made in our understanding of the porosome and the cellular activities required for cell secretion, such as membrane fusion and swelling of secretory vesicles. The discovery of the porosome complex and the molecular mechanism of cell secretion are summarized in this article.

  19. Apple Can Act as Anti-Aging on Yeast Cells

    Directory of Open Access Journals (Sweden)

    Vanessa Palermo

    2012-01-01

    Full Text Available In recent years, epidemiological and biochemical studies have shown that eating apples is associated with reduction of occurrence of cancer, degenerative, and cardiovascular diseases. This association is often attributed to the presence of antioxidants such as ascorbic acid (vitamin C and polyphenols. The substances that hinder the presence of free radicals are also able to protect cells from aging. In our laboratory we used yeast, a unicellular eukaryotic organism, to determine in vivo efficacy of entire apples and their components, such as flesh, skin and polyphenolic fraction, to influence aging and oxidative stress. Our results indicate that all the apple components increase lifespan, with the best result given by the whole fruit, indicating a cooperative role of all apple components.

  20. Cell migration is regulated by AGE-RAGE interaction in human oral cancer cells in vitro.

    Directory of Open Access Journals (Sweden)

    Shun-Yao Ko

    Full Text Available Advanced glycation end products (AGEs are produced in an irreversible non-enzymatic reaction of carbohydrates and proteins. Patients with diabetes mellitus (DM are known to have elevated AGE levels, which is viewed as a risk factor of diabetes-related complications. In a clinical setting, it has been shown that patients with oral cancer in conjunction with DM have a higher likelihood of cancer metastasis and lower cancer survival rates. AGE-RAGE (a receptor of AGEs is also correlated with metastasis and angiogenesis. Recent studies have suggested that the malignancy of cancer may be enhanced by glyceraldehyde-derived AGEs; however, the underlying mechanism remains unclear. This study examined the apparently close correlation between AGE-RAGE and the malignancy of SAS oral cancer cell line. In this study, AGEs increased ERK phosphorylation, enhanced cell migration, and promoted the expression of RAGE, MMP2, and MMP9. Using PD98059, RAGE antibody, and RAGE RNAi to block RAGE pathway resulted in the inhibition of ERK phosphorylation. Cell migration, MMP2 and MMP9 expression were also reduced by this treatment. Our findings demonstrate the importance of AGE-RAGE with regard to the malignancy of oral cancer, and help to explain the poor prognosis of DM subjects with oral cancer.

  1. The Political Structure of Cilicia in Iron Age

    Directory of Open Access Journals (Sweden)

    Mehmet KURT

    2009-06-01

    Full Text Available The plains of Cilicia (Çukurova, which was called Que by the Assyrians, is mentioned as Hume in the Neo-Babylonian sources. The equivalent of Hilakku, which is used for all of the Mountainous Cilicia or at least a part of it n the Assyrian sources, is Pirindu in the Neo-Babylonian texts. Cilicia, consisting of two different regions with completely opposite features; has a geographical dversity with its mountains, rivers, plains and straits. Both the local inscriptions as well as the Assyrian and Neo-Babylonian texts have shown that the geographical diversity had brought a political diversity, too. Thus, an administrational structure with a multiplicity in the local powers and a hierarchy in the political problems was prevalent in the region during the whole Iron Age. Starting from the Neo-Assyrian State, this political organisation, which was provided through the small local kingdoms that were the vassals of the big kingdoms had been applied without any interruption until the occupation of the Macedonian King Alexander the Great.

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

    Science.gov (United States)

    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.

  3. Expression-Invariant Age Estimation Using Structured Learning.

    Science.gov (United States)

    Lou, Zhongyu; Alnajar, Fares; Alvarez, Jose; Hu, Ninghang; Gevers, Theo

    2017-03-08

    In this paper, we investigate and exploit the influence of facial expressions on automatic age estimation. Different from existing approaches, our method jointly learns the age and expression by introducing a new graphical model with a latent layer between the age/expression labels and the features. This layer aims to learn the relationship between the age and expression and captures the face changes which induce the aging and expression appearance, and thus obtaining expression-invariant age estimation. Conducted on three age-expression datasets (FACES [8], Lifespan [20] and NEMO [7]), our experiments illustrate the improvement in performance when the age is jointly learnt with expression in comparison to expression-independent age estimation. The age estimation error is reduced by 14.43%, 37.75% and 9.30% for the FACES, Lifespan and NEMO datasets respectively. The results obtained by our graphical model, without prior-knowledge of the expressions of the tested faces, are better than the best reported ones for all datasets. The flexibility of the proposed model to include more cues is explored by incorporating gender together with age and expression. The results show performance improvements for all cues.

  4. Inexhaustible hair-cell regeneration in young and aged zebrafish

    Directory of Open Access Journals (Sweden)

    Filipe Pinto-Teixeira

    2015-07-01

    Full Text Available Animals have evolved two general strategies to counter injury and maintain physiological function. The most prevalent is protection by isolating vital organs into body cavities. However, protection is not optimal for sensory systems because their external components need to be exposed to the environment to fulfill their receptive function. Thus, a common strategy to maintain sensory abilities against persistent environmental insult involves repair and regeneration. However, whether age or frequent injuries affect the regenerative capacity of sensory organs remains unknown. We have found that neuromasts of the zebrafish lateral line regenerate mechanosensory hair cells after recurrent severe injuries and in adulthood. Moreover, neuromasts can reverse transient imbalances of Notch signaling that result in defective organ proportions during repair. Our results reveal inextinguishable hair-cell regeneration in the lateral line, and suggest that the neuromast epithelium is formed by plastic territories that are maintained by continuous intercellular communication.

  5. Therapeutics with SPION-labeled stem cells for the main diseases related to brain aging: a systematic review

    Science.gov (United States)

    Alvarim, Larissa T; Nucci, Leopoldo P; Mamani, Javier B; Marti, Luciana C; Aguiar, Marina F; Silva, Helio R; Silva, Gisele S; Nucci-da-Silva, Mariana P; DelBel, Elaine A; Gamarra, Lionel F

    2014-01-01

    The increase in clinical trials assessing the efficacy of cell therapy for structural and functional regeneration of the nervous system in diseases related to the aging brain is well known. However, the results are inconclusive as to the best cell type to be used or the best methodology for the homing of these stem cells. This systematic review analyzed published data on SPION (superparamagnetic iron oxide nanoparticle)-labeled stem cells as a therapy for brain diseases, such as ischemic stroke, Parkinson’s disease, amyotrophic lateral sclerosis, and dementia. This review highlights the therapeutic role of stem cells in reversing the aging process and the pathophysiology of brain aging, as well as emphasizing nanotechnology as an important tool to monitor stem cell migration in affected regions of the brain. PMID:25143726

  6. Therapeutics with SPION-labeled stem cells for the main diseases related to brain aging: a systematic review.

    Science.gov (United States)

    Alvarim, Larissa T; Nucci, Leopoldo P; Mamani, Javier B; Marti, Luciana C; Aguiar, Marina F; Silva, Helio R; Silva, Gisele S; Nucci-da-Silva, Mariana P; DelBel, Elaine A; Gamarra, Lionel F

    2014-01-01

    The increase in clinical trials assessing the efficacy of cell therapy for structural and functional regeneration of the nervous system in diseases related to the aging brain is well known. However, the results are inconclusive as to the best cell type to be used or the best methodology for the homing of these stem cells. This systematic review analyzed published data on SPION (superparamagnetic iron oxide nanoparticle)-labeled stem cells as a therapy for brain diseases, such as ischemic stroke, Parkinson's disease, amyotrophic lateral sclerosis, and dementia. This review highlights the therapeutic role of stem cells in reversing the aging process and the pathophysiology of brain aging, as well as emphasizing nanotechnology as an important tool to monitor stem cell migration in affected regions of the brain.

  7. The Vintage Effect in TPF-Growth : An Analysis of the Age Structure of Capital

    NARCIS (Netherlands)

    Gittleman, M.; Ten Raa, T.; Wolff, E.N.

    2003-01-01

    The age structure of capital plays an important role in the measurement of productivity.It has been argued that the slowdown in the 1970 s can be ascribed to the aging of the stock of capital.In this paper we incorporate the age structure in productivity measurement.One proposition proves that Nelso

  8. The nucleolus: a paradigm for cell proliferation and aging.

    Science.gov (United States)

    Comai, L

    1999-12-01

    The nucleolus is the cellular site of ribosome biosynthesis. At this site, active ribosomal DNA (rDNA) genes are rapidly transcribed by RNA polymerase I (pol I) molecules. Recent advances in our understanding of the pol I transcription system have indicated that regulation of ribosomal RNA (rRNA) synthesis is a critical factor in cell growth. Importantly, the same signaling networks that control cell growth and proliferation and are deregulated in cancer appear to control pol I transcription. Therefore, the study of the biochemical basis for growth regulation of pol I transcription can provide basic information about the nuclear signaling network. Hopefully, this information may facilitate the search for drugs that can inhibit the growth of tumor cells by blocking pol I activation. In addition to its function in ribosome biogenesis, recent studies have revealed the prominent role of the nucleolus in cell senescence. These findings have stimulated a new wave of research on the functional relationship between the nucleolus and aging. The aim of this review is to provide an overview of some current topics in the area of nucleolus biology, and it has been written for a general readership.

  9. The nucleolus: a paradigm for cell proliferation and aging

    Directory of Open Access Journals (Sweden)

    Comai L.

    1999-01-01

    Full Text Available The nucleolus is the cellular site of ribosome biosynthesis. At this site, active ribosomal DNA (rDNA genes are rapidly transcribed by RNA polymerase I (pol I molecules. Recent advances in our understanding of the pol I transcription system have indicated that regulation of ribosomal RNA (rRNA synthesis is a critical factor in cell growth. Importantly, the same signaling networks that control cell growth and proliferation and are deregulated in cancer appear to control pol I transcription. Therefore, the study of the biochemical basis for growth regulation of pol I transcription can provide basic information about the nuclear signaling network. Hopefully, this information may facilitate the search for drugs that can inhibit the growth of tumor cells by blocking pol I activation. In addition to its function in ribosome biogenesis, recent studies have revealed the prominent role of the nucleolus in cell senescence. These findings have stimulated a new wave of research on the functional relationship between the nucleolus and aging. The aim of this review is to provide an overview of some current topics in the area of nucleolus biology, and it has been written for a general readership.

  10. Calcium and cell death signaling in neurodegeneration and aging.

    Science.gov (United States)

    Smaili, Soraya; Hirata, Hanako; Ureshino, Rodrigo; Monteforte, Priscila T; Morales, Ana P; Muler, Mari L; Terashima, Juliana; Oseki, Karen; Rosenstock, Tatiana R; Lopes, Guiomar S; Bincoletto, Claudia

    2009-09-01

    Transient increase in cytosolic (Cac2+) and mitochondrial Ca2+ (Ca m2+) are essential elements in the control of many physiological processes. However, sustained increases in Ca c2+ and Ca m2+ may contribute to oxidative stress and cell death. Several events are related to the increase in Ca m2+, including regulation and activation of a number of Ca2+ dependent enzymes, such as phospholipases, proteases and nucleases. Mitochondria and endoplasmic reticulum (ER) play pivotal roles in the maintenance of intracellular Ca2+ homeostasis and regulation of cell death. Several lines of evidence have shown that, in the presence of some apoptotic stimuli, the activation of mitochondrial processes may lead to the release of cytochrome c followed by the activation of caspases, nuclear fragmentation and apoptotic cell death. The aim of this review was to show how changes in calcium signaling can be related to the apoptotic cell death induction. Calcium homeostasis was also shown to be an important mechanism involved in neurodegenerative and aging processes.

  11. A micro-Raman spectroscopic investigation of leukemic U-937 cells in aged cultures

    Science.gov (United States)

    Fazio, Enza; Trusso, Sebastiano; Franco, Domenico; Nicolò, Marco Sebastiano; Allegra, Alessandro; Neri, Fortunato; Musolino, Caterina; Guglielmino, Salvatore P. P.

    2016-04-01

    Recently it has been shown that micro-Raman spectroscopy combined with multivariate analysis is able to discriminate among different types of tissues and tumoral cells by the detection of significant alterations and/or reorganizations of complex biological molecules, such as nucleic acids, lipids and proteins. Moreover, its use, being in principle a non-invasive technique, appears an interesting clinical tool for the evaluation of the therapeutical effects and of the disease progression. In this work we analyzed molecular changes in aged cultures of leukemia model U937 cells with respect to fresh cultures of the same cell line. In fact, structural variations of individual neoplastic cells on aging may lead to a heterogeneous data set, therefore falsifying confidence intervals, increasing error levels of analysis and consequently limiting the use of Raman spectroscopy analysis. We found that the observed morphological changes of U937 cells corresponded to well defined modifications of the Raman contributions in selected spectral regions, where markers of specific functional groups, useful to characterize the cell state, are present. A detailed subcellular analysis showed a change in cellular organization as a function of time, and correlated to a significant increase of apoptosis levels. Besides the aforementioned study, Raman spectra were used as input for principal component analysis (PCA) in order to detect and classify spectral changes among U937 cells.

  12. A strategy to stabilise the local structure of Ti{sup 4+} and Zn{sup 2+} species against aging in TiO{sub 2}/aluminium-doped ZnO bi-layers for applications in hybrid solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Pellegrino, Giovanna; La Magna, Antonino; Bongiorno, Corrado; Smecca, Emanuele; Alberti, Alessandra, E-mail: alessandra.alberti@imm.cnr.it [CNR-IMM Zona Industriale VIII Strada 5, 95121 Catania (Italy); Condorelli, Guglielmo G. [Università degli studi di Catania and INSTM UdR Catania V.le A. Doria 6, Catania (Italy); Mocuta, Cristian [Synchrotron SOLEIL, L' Orme des Merisiers, Saint-Aubin BP 48, 91192, Gif-sur-Yvette Cedex (France)

    2014-08-07

    We explore a strategy to counteract aging issues in TiO{sub 2}/aluminium-doped ZnO bi-layers used in hybrid solar cells photo-anodes, mainly related to Zn diffusion in the TiO{sub 2} matrix. Different Ti{sup 4+} and Zn{sup 2+} local structures within the anatase grains and along the film thickness were found as a function of post-deposition annealing treatments in the range between 200 °C and 500 °C by synchrotron radiation extended x-ray absorption fine structure analyses. In particular, in the 500 °C-treated sample, diffusion of zinc species along the TiO{sub 2} grain-boundaries has been observed with aging (3 years). In contrast, a mild thermal budget at 200 °C favours a proper atomic arrangement of the zinc-containing anatase lattice which reduces Zn diffusion, thus guaranteeing a good stability with aging.

  13. The Genetic Effects of Aging on Human Mesenchymal Stem Cells through Consecutive Subcultures

    Directory of Open Access Journals (Sweden)

    H. Pourjafari

    2013-04-01

    structurally. Our re-sults showed that the aging phenomenon and its consequences such as DNA damages should be considered in the work with consecutive passages of stem cells. Conclusion : We concluded that in our laboratory conditions, the stem cells taken from human umbilical cord blood are only usable for research purposes in early passages (below passage five.We recommend using passages more than five only for educational purposes in our labora-tory; and it is better to do the same work in such research centers. (Sci J Hamadan Univ Med Sci 2013; 20 (1:32-37

  14. Aging behavior of lithium iron phosphate based 18650-type cells studied by in situ neutron diffraction

    Science.gov (United States)

    Paul, Neelima; Wandt, Johannes; Seidlmayer, Stefan; Schebesta, Sebastian; Mühlbauer, Martin J.; Dolotko, Oleksandr; Gasteiger, Hubert A.; Gilles, Ralph

    2017-03-01

    The aging behavior of commercially produced 18650-type Li-ion cells consisting of a lithium iron phosphate (LFP) based cathode and a graphite anode based on either mesocarbon microbeads (MCMB) or needle coke (NC) is studied by in situ neutron diffraction and standard electrochemical techniques. While the MCMB cells showed an excellent cycle life with only 8% relative capacity loss (i.e., referenced to the capacity after formation) after 4750 cycles and showed no capacity loss on storage for two years, the needle coke cells suffered a 23% relative capacity loss after cycling and a 11% loss after storage. Based on a combination of neutron diffraction and electrochemical characterization, it is shown that the entire capacity loss for both cell types is dominated by the loss of active lithium; no other aging mechanisms like structural degradation of anode or cathode active materials or deactivation of active material could be found, highlighting the high structural stability of the active material and the excellent quality of the investigated cells.

  15. Normative and Structural Perspectives on Age in a Work Organization,

    Science.gov (United States)

    1983-12-01

    1978). A comparison of these managers with actual demographic data shows the sample is representative of the population in its age, tenure, and gender ...actual oldest age with the average oldest age judgment. Points that fall on the identity line suggest that the average age judgment is accurate. FIGURE 5...961 #9040 660. 100I I P 0’ es0 CAh Ii -N L5LiC z 0 W IL C5 4 Lo K , 00. W- 1 141U ui c hg -9.8 b. 0 . 04’A4 W C. * 1: . 0 M m&( ;;~L hi o -Ls Ll 0) ts

  16. Blood Cell Mitochondrial DNA Content and Premature Ovarian Aging

    Science.gov (United States)

    Cacciatore, Chiara; Busnelli, Marta; Rossetti, Raffaella; Bonetti, Silvia; Paffoni, Alessio; Mari, Daniela; Ragni, Guido; Persani, Luca; Arosio, M.; Beck-Peccoz, P.; Biondi, M.; Bione, S.; Bruni, V.; Brigante, C.; Cannavo`, S.; Cavallo, L.; Cisternino, M.; Colombo, I.; Corbetta, S.; Crosignani, P.G.; D'Avanzo, M.G.; Dalpra, L.; Danesino, C.; Di Battista, E.; Di Prospero, F.; Donti, E.; Einaudi, S.; Falorni, A.; Foresta, C.; Fusi, F.; Garofalo, N.; Giotti, I.; Lanzi, R.; Larizza, D.; Locatelli, N.; Loli, P.; Madaschi, S.; Maghnie, M.; Maiore, S.; Mantero, F.; Marozzi, A.; Marzotti, S.; Migone, N.; Nappi, R.; Palli, D.; Patricelli, M.G.; Pisani, C.; Prontera, P.; Petraglia, F.; Radetti, G.; Renieri, A.; Ricca, I.; Ripamonti, A.; Rossetti, R.; Russo, G.; Russo, S.; Tonacchera, M.; Toniolo, D.; Torricelli, F.; Vegetti, W.; Villa, N.; Vineis, P.; Wasniewsk, M.; Zuffardi, O.

    2012-01-01

    Primary ovarian insufficiency (POI) is a critical fertility defect characterized by an anticipated and silent impairment of the follicular reserve, but its pathogenesis is largely unexplained. The frequent maternal inheritance of POI together with a remarkable dependence of ovarian folliculogenesis upon mitochondrial biogenesis and bioenergetics suggested the possible involvement of a generalized mitochondrial defect. Here, we verified the existence of a significant correlation between blood and ovarian mitochondrial DNA (mtDNA) content in a group of women undergoing ovarian hyperstimulation (OH), and then aimed to verify whether mtDNA content was significantly altered in the blood cells of POI women. We recruited 101 women with an impaired ovarian reserve: 59 women with premature ovarian failure (POF) and 42 poor responders (PR) to OH. A Taqman copy number assay revealed a significant mtDNA depletion (P<0.001) in both POF and PR women in comparison with 43 women of similar age and intact ovarian reserve, or 53 very old women with a previous physiological menopause. No pathogenic variations in the mitochondrial DNA polymerase γ (POLG) gene were detected in 57 POF or PR women with low blood mtDNA content. In conclusion, blood cell mtDNA depletion is a frequent finding among women with premature ovarian aging, suggesting that a still undetermined but generalized mitochondrial defect may frequently predispose to POI which could then be considered a form of anticipated aging in which the ovarian defect may represent the first manifestation. The determination of mtDNA content in blood may become an useful tool for the POI risk prediction. PMID:22879975

  17. Blood cell mitochondrial DNA content and premature ovarian aging.

    Directory of Open Access Journals (Sweden)

    Marco Bonomi

    Full Text Available Primary ovarian insufficiency (POI is a critical fertility defect characterized by an anticipated and silent impairment of the follicular reserve, but its pathogenesis is largely unexplained. The frequent maternal inheritance of POI together with a remarkable dependence of ovarian folliculogenesis upon mitochondrial biogenesis and bioenergetics suggested the possible involvement of a generalized mitochondrial defect. Here, we verified the existence of a significant correlation between blood and ovarian mitochondrial DNA (mtDNA content in a group of women undergoing ovarian hyperstimulation (OH, and then aimed to verify whether mtDNA content was significantly altered in the blood cells of POI women. We recruited 101 women with an impaired ovarian reserve: 59 women with premature ovarian failure (POF and 42 poor responders (PR to OH. A Taqman copy number assay revealed a significant mtDNA depletion (P<0.001 in both POF and PR women in comparison with 43 women of similar age and intact ovarian reserve, or 53 very old women with a previous physiological menopause. No pathogenic variations in the mitochondrial DNA polymerase γ (POLG gene were detected in 57 POF or PR women with low blood mtDNA content. In conclusion, blood cell mtDNA depletion is a frequent finding among women with premature ovarian aging, suggesting that a still undetermined but generalized mitochondrial defect may frequently predispose to POI which could then be considered a form of anticipated aging in which the ovarian defect may represent the first manifestation. The determination of mtDNA content in blood may become an useful tool for the POI risk prediction.

  18. From cells to organisms: Can we learn about aging from cells in culture?

    Energy Technology Data Exchange (ETDEWEB)

    Campisi, Judith

    2000-12-21

    Can studying cultured cells inform us about the biology of aging? The idea that this may be was stimulated by the first formal description of replicative senescence. Replicative senescence limits the proliferation of normal human cells in culture, causing them to irreversibly arrest growth and adopt striking changes in cell function. We now know that telomere shortening, which occurs in most somatic cells as a consequence of DNA replication, drives replicative senescence in human cells. However, rodent cells also undergo replicative senescence, despite very long telomeres, and DNA damage,the action of certain oncogenes and changes in chromatin induce a phenotype similar to that of replicatively senescent cells. Thus,replicative senescence is an example of the more general process of cellular senescence, indicating that the telomere hypothesis of aging is a misnomer. Cellular senescence appears to be a response to potentially oncogenic insults, including oxidative stress. The growth arrest almost certainly suppresses tumorigenesis, at least in young organisms, whereas the functional changes may contribute to aging,although this has yet to be critically tested. Thus, cellular senescence may be an example of antagonistic pleiotropy.Cross-species comparisons suggest there is a relationship between the senescence of cells in culture and organismal life span, but the relationship is neither quantitative nor direct.

  19. Establishment of induced pluripotent stem cells from aged mice using bone marrow-derived myeloid cells

    Institute of Scientific and Technical Information of China (English)

    Zhao Cheng; Sachiko Ito; Naomi Nishio; Hengyi Xiao; Rong Zhang; Haruhiko Suzuki; Yayoi Okawa; Toyoaki Murohara; Ken-ichi Isobe

    2011-01-01

    If induced pluripotent stem (iPS) cells are to be used to treat damaged tissues or repair organs in elderly patients, it will be necessaryto establish iPS cells from their tissues. To determine the feasibility of using this technology with elderly patients, we asked if itwas indeed possible to establish iPS cells from the bone marrow (BM) of aged mice. BM cells from aged C57BL/6 mice carrying thegreen fluorescence protein (GFP) gene were cultured with granulocyte macrophage-colony stimulating factor (GM-CSF) for 4 days.Four factors (Oct3/4, Sox2, Klf4 and c-Myc) were introduced into the BM-derived myeloid (BM-M) cells. The efficiency of generating iPS cells from aged BM cultured in GM-CSF was low. However, we succeeded in obtaining BM-M-iPS cells from aged C57BL/6 mice,which carried GFP. Our BM-M-iPS cells expressed SSEA-1 and Pou5f1 and were positive for alkaline phosphatase staining. The iPScells did make teratoma with three germ layers following injection into syngeneic C57BL/6 mice, and can be differentiated to threegerm layers in vitro. By co-culturing with OP9, the BM-M-iPS cells can be differentiated to the myeloid lineage. The differentiated BM-M-iPS cells proliferated well in the presence of GM-CSF, and lost expression of Nanog and Pou5f1, at least in part, due to methylation of their promoters. On the contrary, Tnf and Il1b gene expression was upregulated and their promoters were hypornethylated.

  20. Protection of Acanthopanax Senticosus Saponin on Free Radical Injury Induced Aging of Nerve Cell

    Institute of Scientific and Technical Information of China (English)

    潘永进; 顾永健; 顾小苏

    2002-01-01

    Objective: To study the effect of Acanthopanax senticosus saponin (ASS) on free radical injury induced neuron aging. Methods: On day 7 of fetal mice, cortical neuron primary passage cultures were divided into the normal control group, model group and ASS groups. The model group using free radical (FeSO4 plus H2O2) injury mode prepared in vivo cultured ICR mice cortical neuron aging model; ASS groups: 24 hrs before and after treated with H2O2 and FeSO4, different concentration of ASS was added, according to biochemical parameters such as lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA) etc. and histomorphologic change to observe the protection of ASS on aging neurons. Results: The LDH, SOD, MDA of the model group were compared with the normal group, P<0.01; ASS groups added 1.25 mg/100 ml, 2.5 mg/100 ml, 5 mg/100 ml concentration of ASS, their LDH, SOD, MDA compared with the model group P<0.05-0.01, the difference was significant. In medicated groups the SOD activity of oxidization injured nerve cells obviously elevated, LDH activity and MDA content apparently lowered. Microscope and scanning electron microscopic observation showed that supplemented with ASS to protect the nerve cell injury abated, part of the cellular structure tended to normalize. Conclusion: ASS could act against free radical toxic effect, increase the anti-oxidase activity, strengthen the protection of neuron cells. It is assumed that the effect against nerve cell aging was possibly through scavenging oxygen free radical, strengthening the stability of cell membrane, thus delaying the development of aging.

  1. 76 FR 74831 - Aging Management of Stainless Steel Structures and Components in Treated Borated Water

    Science.gov (United States)

    2011-12-01

    ... COMMISSION Aging Management of Stainless Steel Structures and Components in Treated Borated Water AGENCY...- ISG-2011-01, ``Aging Management of Stainless Steel Structures and Components in Treated Borated Water... management of stainless steel structures and components exposed to treated borated water. In response to...

  2. Lens Epithelial Cell Proliferation and Cell Density in Human Age-related Cataract

    Institute of Scientific and Technical Information of China (English)

    Xialin Liu; Yizhi Liu; Jianliang Zheng; Qiang Huang; Huling Zheng

    2000-01-01

    Purpose: To discuss the potential effect of the lens epithelial cell proliferation in age-related cataract.Methods: In vitro cell proliferation was assayed by MTT method to evaluate the lens epithelial cell density, index, and proliferation capacity in normal lens and all kinds of age-related cataract. Capsulotomy specimens from all kinds of patients who underwent cataract phacoemulsification extraction surgery were compared with the lens epithelial specimens from non-cataract lenses of Eye Bank eyes.Results: Lens epithelial cell density of central anterior capsule (LECD) in female normal lens was higher than that in male, LECD in nuclear cataract( > NⅢ ) was higher than that in normal lens, but in the mature cortical cataract, LF CD was lower. Mitotic index of three kinds of age-related cataracts in vivo had no statistical difference, neither did cell proliferation capacity of cultivated cells in vitro.Conclusion: The individual difference of lens epithelial cell density and proliferation capacity in vivo may be an important underlying cause for senile cataract in the cellular level, especially for nuclear cataract.

  3. Signaling pathway activation drift during aging: Hutchinson-Gilford Progeria Syndrome fibroblasts are comparable to normal middle-age and old-age cells.

    Science.gov (United States)

    Aliper, Alexander M; Csoka, Antonei Benjamin; Buzdin, Anton; Jetka, Tomasz; Roumiantsev, Sergey; Moskalev, Alexy; Zhavoronkov, Alex

    2015-01-01

    For the past several decades, research in understanding the molecular basis of human aging has progressed significantly with the analysis of premature aging syndromes. Progerin, an altered form of lamin A, has been identified as the cause of premature aging in Hutchinson-Gilford Progeria Syndrome (HGPS), and may be a contributing causative factor in normal aging. However, the question of whether HGPS actually recapitulates the normal aging process at the cellular and organismal level, or simply mimics the aging phenotype is widely debated. In the present study we analyzed publicly available microarray datasets for fibroblasts undergoing cellular aging in culture, as well as fibroblasts derived from young, middle-age, and old-age individuals, and patients with HGPS. Using GeroScope pathway analysis and drug discovery platform we analyzed the activation states of 65 major cellular signaling pathways. Our analysis reveals that signaling pathway activation states in cells derived from chronologically young patients with HGPS strongly resemble cells taken from normal middle-aged and old individuals. This clearly indicates that HGPS may truly represent accelerated aging, rather than being just a simulacrum. Our data also points to potential pathways that could be targeted to develop drugs and drug combinations for both HGPS and normal aging.

  4. Delayed animal aging through the recovery of stem cell senescence by platelet rich plasma.

    Science.gov (United States)

    Liu, Hen-Yu; Huang, Chiung-Fang; Lin, Tzu-Chieh; Tsai, Ching-Yu; Tina Chen, Szu-Yu; Liu, Alice; Chen, Wei-Hong; Wei, Hong-Jian; Wang, Ming-Fu; Williams, David F; Deng, Win-Ping

    2014-12-01

    Aging is related to loss of functional stem cell accompanying loss of tissue and organ regeneration potentials. Previously, we demonstrated that the life span of ovariectomy-senescence accelerated mice (OVX-SAMP8) was significantly prolonged and similar to that of the congenic senescence-resistant strain of mice after platelet rich plasma (PRP)/embryonic fibroblast transplantation. The aim of this study is to investigate the potential of PRP for recovering cellular potential from senescence and then delaying animal aging. We first examined whether stem cells would be senescent in aged mice compared to young mice. Primary adipose derived stem cells (ADSCs) and bone marrow derived stem cells (BMSCs) were harvested from young and aged mice, and found that cell senescence was strongly correlated to animal aging. Subsequently, we demonstrated that PRP could recover cell potential from senescence, such as promote cell growth (cell proliferation and colony formation), increase osteogenesis, decrease adipogenesis, restore cell senescence related markers and resist the oxidative stress in stem cells from aged mice. The results also showed that PRP treatment in aged mice could delay mice aging as indicated by survival, body weight and aging phenotypes (behavior and gross morphology) in term of recovering the cellular potential of their stem cells compared to the results on aged control mice. In conclusion these findings showed that PRP has potential to delay aging through the recovery of stem cell senescence and could be used as an alternative medicine for tissue regeneration and future rejuvenation.

  5. Multilayer solar cell waveguide structures containing metamaterials

    Science.gov (United States)

    Hamouche, Houria.; Shabat, Mohammed. M.; Schaadt, Daniel M.

    2017-01-01

    Multilayer antireflection coating structures made from silicon and metamaterials are designed and investigated using the Transfer Matrix Method (TMM). The Transfer Matrix Method is a very useful algorithm for the analysis of periodic structures. We investigate in this paper two anti-reflection coating structures for silicon solar cells with a metamaterial film layer. In the first structure, the metamaterial film layer is sandwiched between a semi-infinite glass cover layer and a semi-infinite silicon substrate layer. The second structure consists of a four layers, a pair of metamaterial-dielectric layer with opposite real part of refractive indices, is placed between the two semi-infinite cover and substrate. We have simulated the absorptivity property of the structures for adjustable thicknesses by using MAPLE software. The absorptivity of the structures achieves greater than 80% for incident electromagnetic wave of transverse magnetic (TM) polarization.

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

    Directory of Open Access Journals (Sweden)

    Christopher P. Ardeljan

    2014-12-01

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

  7. Challenges in structural approaches to cell modeling.

    Science.gov (United States)

    Im, Wonpil; Liang, Jie; Olson, Arthur; Zhou, Huan-Xiang; Vajda, Sandor; Vakser, Ilya A

    2016-07-31

    Computational modeling is essential for structural characterization of biomolecular mechanisms across the broad spectrum of scales. Adequate understanding of biomolecular mechanisms inherently involves our ability to model them. Structural modeling of individual biomolecules and their interactions has been rapidly progressing. However, in terms of the broader picture, the focus is shifting toward larger systems, up to the level of a cell. Such modeling involves a more dynamic and realistic representation of the interactomes in vivo, in a crowded cellular environment, as well as membranes and membrane proteins, and other cellular components. Structural modeling of a cell complements computational approaches to cellular mechanisms based on differential equations, graph models, and other techniques to model biological networks, imaging data, etc. Structural modeling along with other computational and experimental approaches will provide a fundamental understanding of life at the molecular level and lead to important applications to biology and medicine. A cross section of diverse approaches presented in this review illustrates the developing shift from the structural modeling of individual molecules to that of cell biology. Studies in several related areas are covered: biological networks; automated construction of three-dimensional cell models using experimental data; modeling of protein complexes; prediction of non-specific and transient protein interactions; thermodynamic and kinetic effects of crowding; cellular membrane modeling; and modeling of chromosomes. The review presents an expert opinion on the current state-of-the-art in these various aspects of structural modeling in cellular biology, and the prospects of future developments in this emerging field.

  8. Energy metabolism and metabolic sensors in stem cells: the metabostem crossroads of aging and cancer.

    Science.gov (United States)

    Menendez, Javier A; Joven, Jorge

    2014-01-01

    We are as old as our adult stem cells are; therefore, stem cell exhaustion is considered a hallmark of aging. Our tumors are as aggressive as the number of cancer stem cells (CSCs) they bear because CSCs can survive treatments with hormones, radiation, chemotherapy, and molecularly targeted drugs, thus increasing the difficulty of curing cancer. Not surprisingly, interest in stem cell research has never been greater among members of the public, politicians, and scientists. But how can we slow the rate at which our adult stem cells decline over our lifetime, reducing the regenerative potential of tissues, while efficiently eliminating the aberrant, life-threatening activity of "selfish", immortal, and migrating CSCs? Frustrated by the gene-centric limitations of conventional approaches to aging diseases, our group and other groups have begun to appreciate that bioenergetic metabolism, i.e., the production of fuel & building blocks for growth and division, and autophagy/mitophagy, i.e., the quality-control, self-cannibalistic system responsible for "cleaning house" and "recycling the trash", can govern the genetic and epigenetic networks that facilitate stem cell behaviors. Indeed, it is reasonable to suggest the existence of a "metabostem" infrastructure that operates as a shared hallmark of aging and cancer, thus making it physiologically plausible to maintain or even increase the functionality of adult stem cells while reducing the incidence of cancer and extending the lifespan. This "metabostemness" property could lead to the discovery of new drugs that reprogram cell metabotypes to increase the structural and functional integrity of adult stem cells and positively influence their lineage determination, while preventing the development and aberrant function of stem cells in cancer tissues. While it is obvious that the antifungal antibiotic rapamycin, the polyphenol resveratrol, and the biguanide metformin already belong to this new family of metabostemness

  9. [Immature-cell leukoses in the adult age].

    Science.gov (United States)

    Fleischer, J; Morgenstern, D; Richter, W

    1976-04-01

    In form of a survey the author enters into selected questions of the etiopathogenesis, the pre-leucaemic phase, the epidemiology, the cytochemical subdivision, the clinic and therapy of undifferentiated cell leucaemia in adult age. The number of two-year sojourns in a hospital and other data are reported on the basis of an evaluation of the signature ledges of the clinical histories in the district Dresden. A study concerning the therapy carried out on 331 patients from six clinics of the GDR emphasizes the value of the polychemotherapy, in which cases according to the COAP- and ViDaP-scheme the results of the treatment are somewhat more unfavourable, compared with the results in the newest combinations of other authors.

  10. Nuclear power plant life extension: How aging affects performance of containments & other structures

    Institute of Scientific and Technical Information of China (English)

    Robert A Dameron; Sun Junling

    2013-01-01

    This paper focuses on how aging can affect performance of safety-related structures in nuclear power plant (NPP).Knowledge and assessment of impacts of aging on structures are essential to plant life extension analysis,especially performance to severe loadings such as loss-of-coolant-accidents or major seismic events.Plant life extension issues are of keen interest in countries (like the United States) which have a large,aging fleet of NPPs.This paper addresses the overlap and relationship of structure aging to severe loading performance,with particular emphasis on containment structures.

  11. Planarians as a model of aging to study the interaction between stem cells and senescent cells in vivo

    Directory of Open Access Journals (Sweden)

    Patrick M. Perrigue

    2015-12-01

    Full Text Available The depletion of stem cell pools and the accumulation of senescent cells in animal tissues are linked to aging. Planarians are invertebrate flatworms and are unusual in that their stem cells, called neoblasts, are constantly replacing old and dying cells. By eliminating neoblasts in worms via irradiation, the biological principles of aging are exposed in the absence of wound healing and regeneration, making planaria a powerful tool for aging research.

  12. No dramatic age-related loss of hair cells and spiral ganglion neurons in Bcl-2 over-expression mice or Bax null mice

    Directory of Open Access Journals (Sweden)

    Ohlemiller Kevin K

    2010-07-01

    Full Text Available Abstract Age-related decline of neuronal function is associated with age-related structural changes. In the central nervous system, age-related decline of cognitive performance is thought to be caused by synaptic loss instead of neuronal loss. However, in the cochlea, age-related loss of hair cells and spiral ganglion neurons (SGNs is consistently observed in a variety of species, including humans. Since age-related loss of these cells is a major contributing factor to presbycusis, it is important to study possible molecular mechanisms underlying this age-related cell death. Previous studies suggested that apoptotic pathways were involved in age-related loss of hair cells and SGNs. In the present study, we examined the role of Bcl-2 gene in age-related hearing loss. In one transgenic mouse line over-expressing human Bcl-2, there were no significant differences between transgenic mice and wild type littermate controls in their hearing thresholds during aging. Histological analysis of the hair cells and SGNs showed no significant conservation of these cells in transgenic animals compared to the wild type controls during aging. These data suggest that Bcl-2 overexpression has no significant effect on age-related loss of hair cells and SGNs. We also found no delay of age-related hearing loss in mice lacking Bax gene. These findings suggest that age-related hearing loss is not through an apoptotic pathway involving key members of Bcl-2 family.

  13. Preferential retrotransposition in aging yeast mother cells is correlated with increased genome instability.

    Science.gov (United States)

    Patterson, Melissa N; Scannapieco, Alison E; Au, Pak Ho; Dorsey, Savanna; Royer, Catherine A; Maxwell, Patrick H

    2015-10-01

    Retrotransposon expression or mobility is increased with age in multiple species and could promote genome instability or altered gene expression during aging. However, it is unclear whether activation of retrotransposons during aging is an indirect result of global changes in chromatin and gene regulation or a result of retrotransposon-specific mechanisms. Retromobility of a marked chromosomal Ty1 retrotransposon in Saccharomyces cerevisiae was elevated in mother cells relative to their daughter cells, as determined by magnetic cell sorting of mothers and daughters. Retromobility frequencies in aging mother cells were significantly higher than those predicted by cell age and the rate of mobility in young populations, beginning when mother cells were only several generations old. New Ty1 insertions in aging mothers were more strongly correlated with gross chromosome rearrangements than in young cells and were more often at non-preferred target sites. Mother cells were more likely to have high concentrations and bright foci of Ty1 Gag-GFP than their daughter cells. Levels of extrachromosomal Ty1 cDNA were also significantly higher in aged mother cell populations than their daughter cell populations. These observations are consistent with a retrotransposon-specific mechanism that causes retrotransposition to occur preferentially in yeast mother cells as they begin to age, as opposed to activation by phenotypic changes associated with very old age. These findings will likely be relevant for understanding retrotransposons and aging in many organisms, based on similarities in regulation and consequences of retrotransposition in diverse species.

  14. The age structure of the Milky Way's halo

    CERN Document Server

    Carollo, Daniela; Placco, Vinicius; Santucci, Rafael; Denissenkov, Pavel; Tissera, Patricia; Lentner, Geoffrey; Rossi, Silvia; Lee, Young Sun; Tumlinson, Jason

    2016-01-01

    We present a new, high-resolution chronographic (age) map of the Milky Way's halo, based on the inferred ages of ~130,000 field blue horizontal-branch (BHB) stars with photometry from the Sloan Digital Sky Survey. Our map exhibits a strong central concentration of BHB stars with ages greater than 12 Gyr, extending up to ~15 kpc from the Galactic center (reaching close to the solar vicinity), and a decrease in the mean ages of field stars with distance by 1-1.5 Gyr out to ~45-50 kpc, along with an apparent increase of the dispersion of stellar ages, and numerous known (and previously unknown) resolved over-densities and debris streams, including the Sagittarius Stream. These results agree with expectations from modern LambdaCDM cosmological simulations, and support the existence of a dual (inner/outer) halo system, punctuated by the presence of over-densities and debris streams that have not yet completely phase-space mixed.

  15. The age structure of the Milky Way's halo

    Science.gov (United States)

    Carollo, D.; Beers, T. C.; Placco, V. M.; Santucci, R. M.; Denissenkov, P.; Tissera, P. B.; Lentner, G.; Rossi, S.; Lee, Y. S.; Tumlinson, J.

    2016-12-01

    We present a new, high-resolution chronographic (age) map of the Milky Way's halo, based on the inferred ages of ~130,000 field blue horizontal-branch (BHB) stars with photometry from the Sloan Digital Sky Survey. Our map exhibits a strong central concentration of BHB stars with ages greater than 12 Gyr, extending up to ~15 kpc from the Galactic Centre (reaching close to the solar vicinity), and a decrease in the mean ages of field stars with distance by 1-1.5 Gyr out to ~45-50 kpc, along with an apparent increase of the dispersion of stellar ages, and numerous known (and previously unknown) resolved over-densities and debris streams, including the Sagittarius Stream. These results agree with expectations from modern lambda cold dark matter cosmological simulations, and support the existence of a dual (inner/outer) halo system, punctuated by the presence of over-densities and debris streams that have not yet completely phase-space mixed.

  16. [Structure of the articular cartilage in the middle aged].

    Science.gov (United States)

    Kop'eva, T N; Mul'diiarov, P Ia; Bel'skaia, O B; Pastel', V B

    1983-10-01

    In persons 17-83 years of age having no articular disorders 39 samples of the patellar articular cartilage, the articulated surface and the femoral head have been studied histochemically, histometrically and electron microscopically. Age involution of the articular cartilage is revealed after 40 years of age as a progressive decrease in chondrocytes density in the superficial and (to a less degree) in the intermediate zones. This is accompanied with a decreasing number of 3- and 4-cellular lacunae and with an increasing number of unicellular and hollow lacunae. In some chondrocytes certain distrophic and necrotic changes are revealed. In the articular matrix the zone with the minimal content of glycosaminoglycans becomes thicker and keratansulfate content in the territorial matrix of the cartilage deep zone grows large.

  17. The Analysis of the Age Structure of Regional Fixed Capital in the Agriculture

    Directory of Open Access Journals (Sweden)

    P. Mazouch

    2016-06-01

    Full Text Available The paper deals with an estimate and analysis of the value of regional net fixed capital stock and the age structure of machinery and equipment in Czech agriculture. In order to perform such analysis, the official model of perpetual inventory method is transformed into the Markov chain model and applied on regional data separately. Regional net fixed capital stock is presented for the period of 2008-2013. The development of the average age of machinery and equipment comprises a potential indicator of the modernisation process in the industry. The analysis of the age structure is based on the structure heterogeneity indicator. For these purposes, the real age structure in each Czech region is compared with the theoretical stable and stationary structure. Currently, the most heterogeneous age structure of machinery and equipment occurs in Prague and the Karlovy Vary region.

  18. SIR epidemic models with age structure and immigration

    OpenAIRE

    Franceschetti, Andrea

    2006-01-01

    The aim of the present work is to discuss some aspects about a problem of epidemiological modeling, the evolution of a childhood infectious disease in a human population subject to immigration and in which age-strucure is taken into account.

  19. The Frontal Hypothesis of Cognitive Aging: Factor Structure and Age Effects on Four "Frontal Tests" among Healthy Individuals

    Science.gov (United States)

    Rodriguez-Aranda, Claudia; Sundet, Kjetil

    2006-01-01

    With 101 healthy aging adult participants, the authors investigated whether executive functions are a unitary concept. The authors established the factor structure of the Wisconsin Card Sorting Test (WCST; E. A. Berg, 1948), the Stroop color and word test (C. J. Golden, 1978), verbal fluency using the Controlled Oral Word Association Test (COWAT;…

  20. Proteomics and aging : studying the influence of aging on endothelial cells and human plasma

    NARCIS (Netherlands)

    Eman, M.R.

    2007-01-01

    In general, human aging is considered one of the most complex and less-well understood process in biology. In this thesis the possibilities of proteomics technology in the field of aging were explored. The complexity of the aging process was supposed to accompanied by relatively subtle proteome vari

  1. Age-structure-dependent recruitment: a meta-analysis applied to Northeast Atlantic fish stocks

    NARCIS (Netherlands)

    Brunel, T.P.A.

    2010-01-01

    Exploitation alters the age structure of fish stocks. Several stock-specific studies have suggested that changes in the age structure might have consequences for subsequent recruitment, but the evidence is not universal. To investigate how common such effects are among 39 Northeast Atlantic fish sto

  2. 76 FR 69292 - Aging Management of Stainless Steel Structures and Components in Treated Borated Water

    Science.gov (United States)

    2011-11-08

    ... COMMISSION Aging Management of Stainless Steel Structures and Components in Treated Borated Water AGENCY... Staff Guidance (LR-ISG), LR- ISG-2011-01, ``Aging Management of Stainless Steel Structures and Components in Treated Borated Water.'' This LR-ISG revises the guidance in the Standard Review Plan...

  3. Generation time, net reproductive rate, and growth in stage-age-structured populations

    DEFF Research Database (Denmark)

    Steiner, Uli; Tuljapurkar, Shripad; Coulson, Tim

    2014-01-01

    to age-structured populations. Here we generalize this result to populations structured by stage and age by providing a new, unique measure of reproductive timing (Tc) that, along with net reproductive rate (R0), has a direct mathematical relationship to and approximates growth rate (r). We use simple...

  4. Calcium and cell death signaling in neurodegeneration and aging

    Directory of Open Access Journals (Sweden)

    Soraya Smaili

    2009-09-01

    Full Text Available Transient increase in cytosolic (Cac2+ and mitochondrial Ca2+ (Ca m2+ are essential elements in the control of many physiological processes. However, sustained increases in Ca c2+ and Ca m2+ may contribute to oxidative stress and cell death. Several events are related to the increase in Ca m2+, including regulation and activation of a number of Ca2+ dependent enzymes, such as phospholipases, proteases and nucleases. Mitochondria and endoplasmic reticulum (ER play pivotal roles in the maintenance of intracellular Ca2+ homeostasis and regulation of cell death. Several lines of evidence have shown that, in the presence of some apoptotic stimuli, the activation of mitochondrial processes maylead to the release of cytochrome c followed by the activation of caspases, nuclear fragmentation and apoptotic cell death. The aim of this review was to show how changes in calcium signaling can be related to the apoptotic cell death induction. Calcium homeostasis was also shown to be an important mechanism involved in neurodegenerative and aging processes.Aumentos transientes no cálcio citosólico (Ca c2+ e mitocondrial (Ca m2+ são elementos essenciais no controle de muitos processos fisiológicos. No entanto, aumentos sustentados do Ca c2+ e do Ca m2+ podem contribuir para o estresse oxidativo ea morte celular. Muitos eventos estão relacionados ao aumentono Ca c2+, incluindo a regulação e ativação de várias enzimas dependentes de Ca2+ como as fosfolipases, proteases e nucleases. A mitocôndria e o retículo endoplasmático têm um papel central na manutenção da homeostase intracellular de Ca c2+ e na regulação da morte celular. Várias evidências mostraram que, na presença de certos estímulos apoptóticos, a ativação dos processos mitocondriais pode promover a liberação de citocromo c, seguida da ativação de caspases, fragmentação nuclear e morte celular por apoptose. O objetivo desta revisão é mostrar como aumentos na sinalização de

  5. Aging Studies of Sr-doped LaCrO3/YSZ/Pt Cells for an Electrochemical NOx Sensor

    Energy Technology Data Exchange (ETDEWEB)

    Song, S; Martin, L P; Glass, R S; Murray, E P; Visser, J H; Soltis, R E; Novak, R F; Kubinski, D J

    2005-10-05

    The stability and NO{sub x} sensing performance of electrochemical cells of the structure Sr-doped LaCrO{sub 3-{delta}} (LSC)/yttria-stabilized zirconia (YSZ)/Pt are being investigated for use in NO{sub x} aftertreatment systems in diesel vehicles. Among the requirements for NO{sub x} sensor materials in these systems are stability and long lifetime (up to ten years) in the exhaust environment. In this study, cell aging effects were explored following extended exposure to a test environment of 10% O{sub 2} at operating temperatures of 600-700 C. The data show that aging results in changes in particle morphology, chemical composition and interfacial structure, Impedance spectroscopy indicated an initial increase in the cell resistance during the early stages of aging, which is correlated to densification of the Pt electrode. Also, x-ray photoelectron spectroscopy indicated formation of SrZrO{sub 2} solid state reaction product in the LSC, a process which is of finite duration. Subsequently, the overall cell resistance decreases with aging time due, in part, to roughening of YSZ-LSC interface, which improves interface adherence and enhances charge transfer kinetics at the O{sub 2}/YSZ/LSC triple phase boundary. This study constitutes a first step in the development of a basic understanding of aging phenomena in solid state electrochemical systems with application not only to sensors, but also to fuel cells, membranes, and electrolyzers.

  6. Who Ate Whom: Population Dynamics With Age-Structured Predation

    Science.gov (United States)

    2010-10-15

    competes for food. Werner and Gilliam [2] review many examples of ecosystems in which competitive and predatory relationships are age- and size-dependent. As...of reproduction in that it transfers biomass from tadpoles to frogs, though it is certainly not identical. We have not fully explored the relationship ...limit cycles, though the limit cycles are not robust and rather unrealistic biologically, so in this model the two species are completely codependent

  7. Prevalence and structure of periodontal disease in young aged adults

    OpenAIRE

    Kholodnyak, O. V.

    2017-01-01

    Under modern condotions the problem of prevention and treatment of periodontal does not lose its relevance, This is significant prevalence of periodontal lesions, including young people. One of the promising areas that help to reduce the incidence and intensity of periodontal disease is the development and implementation of objective methods for predicting and preventing their development. Data on periodontal status in young aged adults are contradictory, and rates of prevalence of periodonta...

  8. Nanoscale Structure, Dynamics, and Aging Behavior of Metallic Glass Thin Films

    Science.gov (United States)

    Burgess, J. A. J.; Holt, C. M. B.; Luber, E. J.; Fortin, D. C.; Popowich, G.; Zahiri, B.; Concepcion, P.; Mitlin, D.; Freeman, M. R.

    2016-01-01

    Scanning tunnelling microscopy observations resolve the structure and dynamics of metallic glass Cu100−xHfx films and demonstrate scanning tunnelling microscopy control of aging at a metallic glass surface. Surface clusters exhibit heterogeneous hopping dynamics. Low Hf concentration films feature an aged surface of larger, slower clusters. Argon ion-sputtering destroys the aged configuration, yielding a surface in constant fluctuation. Scanning tunnelling microscopy can locally restore the relaxed state, allowing for nanoscale lithographic definition of aged sections. PMID:27498698

  9. Nanoscale Structure, Dynamics, and Aging Behavior of Metallic Glass Thin Films.

    Science.gov (United States)

    Burgess, J A J; Holt, C M B; Luber, E J; Fortin, D C; Popowich, G; Zahiri, B; Concepcion, P; Mitlin, D; Freeman, M R

    2016-08-08

    Scanning tunnelling microscopy observations resolve the structure and dynamics of metallic glass Cu100-xHfx films and demonstrate scanning tunnelling microscopy control of aging at a metallic glass surface. Surface clusters exhibit heterogeneous hopping dynamics. Low Hf concentration films feature an aged surface of larger, slower clusters. Argon ion-sputtering destroys the aged configuration, yielding a surface in constant fluctuation. Scanning tunnelling microscopy can locally restore the relaxed state, allowing for nanoscale lithographic definition of aged sections.

  10. The effect of sol aging time on Structural and Optical properties of sol gel ZnO doped Al

    Science.gov (United States)

    El Hallani, G.; Fazouan, N.; Liba, A.; Khuili, M.

    2016-10-01

    Currently the doped or undoped ZnO semiconductor is of great importance in the field of electronic and optoelectronic devices such as transparent conductors and optical windows of solar cells based on silicon. ZnO thin films are produced by several techniques such as sol-gel method which is a chemical technique usually dependent on solution conditions. However, the sol gel aging time is an important parameter, which can have a significant impact on the properties of thin films. In this work we studied the effect of aging times (0h, 24h, 48h, 72h, 1 week) of the precursor solution on the structural and optical properties of ZnO doped Al (3 at.%). Thin films prepared by spin coating on glass substrates were investigated. The X-ray diffraction (XRD) analysis shows that the ZnO doped Al (3 at.%) exhibit the hexagonal wurtzite structure with a preferential orientation along [002] direction. The shift of (002) peaks towards higher diffraction angles is observed with sol aging time and also, a variation of crystallite sizes and thickness of thin films are shown with increasing sol aging time. All films present an average optical transmittance around 90% in the visible range with some interference fringes indicating a relative smoothness of films. We note an increasing in transmittance level with sol aging time from 0h to 48h. We can conclude that the aging times of the precursor solution influences the structural and optical properties of studied thin films.

  11. A Structured Population Model of Cell Differentiation

    CERN Document Server

    Doumic, Marie; Perthame, Benoit; Zubelli, Jorge P

    2010-01-01

    We introduce and analyze several aspects of a new model for cell differentiation. It assumes that differentiation of progenitor cells is a continuous process. From the mathematical point of view, it is based on partial differential equations of transport type. Specifically, it consists of a structured population equation with a nonlinear feedback loop. This models the signaling process due to cytokines, which regulate the differentiation and proliferation process. We compare the continuous model to its discrete counterpart, a multi-compartmental model of a discrete collection of cell subpopulations recently proposed by Marciniak-Czochra et al. in 2009 to investigate the dynamics of the hematopoietic system. We obtain uniform bounds for the solutions, characterize steady state solutions, and analyze their linearized stability. We show how persistence or extinction might occur according to values of parameters that characterize the stem cells self-renewal. We also perform numerical simulations and discuss the q...

  12. Age-related changes in rat bone-marrow mesenchymal stem cell plasticity

    Directory of Open Access Journals (Sweden)

    Chase P Bryant

    2011-10-01

    Full Text Available Abstract Background The efficacy of adult stem cells is known to be compromised as a function of age. This therefore raises questions about the effectiveness of autologous cell therapy in elderly patients. Results We demonstrated that the expression profile of stemness markers was altered in BM-MSCs derived from old rats. BM-MSCs from young rats (4 months expressed Oct-4, Sox-2 and NANOG, but we failed to detect Sox-2 and NANOG in BM-MSCs from older animals (15 months. Chondrogenic, osteogenic and adipogenic potential is compromised in old BM-MSCs. Stimulation with a cocktail mixture of bone morphogenetic protein (BMP-2, fibroblast growth factor (FGF-2 and insulin-like growth factor (IGF-1 induced cardiomyogenesis in young BM-MSCs but not old BM-MSCs. Significant differences in the expression of gap junction protein connexin-43 were observed between young and old BM-MSCs. Young and old BM-MSCs fused with neonatal ventricular cardiomyocytes in co-culture and expressed key cardiac transcription factors and structural proteins. Cells from old animals expressed significantly lower levels of VEGF, IGF, EGF, and G-CSF. Significantly higher levels of DNA double strand break marker γ-H2AX and diminished levels of telomerase activity were observed in old BM-MSCs. Conclusion The results suggest age related differences in the differentiation capacity of BM-MSCs. These changes may affect the efficacy of BM-MSCs for use in stem cell therapy.

  13. Derivation of stochastic partial differential equations for size- and age-structured populations.

    Science.gov (United States)

    Allen, Edward J

    2009-01-01

    Stochastic partial differential equations (SPDEs) for size-structured and age- and size-structured populations are derived from basic principles, i.e. from the changes that occur in a small time interval. Discrete stochastic models of size-structured and age-structured populations are constructed, carefully taking into account the inherent randomness in births, deaths, and size changes. As the time interval decreases, the discrete stochastic models lead to systems of Itô stochastic differential equations. As the size and age intervals decrease, SPDEs are derived for size-structured and age- and size-structured populations. Comparisons between numerical solutions of the SPDEs and independently formulated Monte Carlo calculations support the accuracy of the derivations.

  14. Healthy aging and myocardium: A complicated process with various effects in cardiac structure and physiology.

    Science.gov (United States)

    Nakou, E S; Parthenakis, F I; Kallergis, E M; Marketou, M E; Nakos, K S; Vardas, P E

    2016-04-15

    It is known that there is an ongoing increase in life expectancy worldwide, especially in the population older than 65years of age. Cardiac aging is characterized by a series of complex pathophysiological changes affecting myocardium at structural, cellular, molecular and functional levels. These changes make the aged myocardium more susceptible to stress, leading to a high prevalence of cardiovascular diseases (heart failure, atrial fibrillation, left ventricular hypertrophy, coronary artery disease) in the elderly population. The aging process is genetically programmed but modified by environmental influences, so that the rate of aging can vary widely among people. We summarized the entire data concerning all the multifactorial changes in aged myocardium and highlighting the recent evidence for the pathophysiological basis of cardiac aging. Keeping an eye on the clinical side, this review will explore the potential implications of the age-related changes in the clinical management and on novel therapeutic strategies potentially deriving from the scientific knowledge currently acquired on cardiac aging process.

  15. The circadian clock in skin: implications for adult stem cells, tissue regeneration, cancer, aging, and immunity.

    Science.gov (United States)

    Plikus, Maksim V; Van Spyk, Elyse N; Pham, Kim; Geyfman, Mikhail; Kumar, Vivek; Takahashi, Joseph S; Andersen, Bogi

    2015-06-01

    Historically, work on peripheral circadian clocks has been focused on organs and tissues that have prominent metabolic functions, such as the liver, fat, and muscle. In recent years, skin has emerged as a model for studying circadian clock regulation of cell proliferation, stem cell functions, tissue regeneration, aging, and carcinogenesis. Morphologically, skin is complex, containing multiple cell types and structures, and there is evidence for a functional circadian clock in most, if not all, of its cell types. Despite the complexity, skin stem cell populations are well defined, experimentally tractable, and exhibit prominent daily cell proliferation cycles. Hair follicle stem cells also participate in recurrent, long-lasting cycles of regeneration: the hair growth cycles. Among other advantages of skin is a broad repertoire of available genetic tools enabling the creation of cell type-specific circadian mutants. Also, due to the accessibility of skin, in vivo imaging techniques can be readily applied to study the circadian clock and its outputs in real time, even at the single-cell level. Skin provides the first line of defense against many environmental and stress factors that exhibit dramatic diurnal variations such as solar ultraviolet (UV) radiation and temperature. Studies have already linked the circadian clock to the control of UVB-induced DNA damage and skin cancers. Due to the important role that skin plays in the defense against microorganisms, it also represents a promising model system to further explore the role of the clock in the regulation of the body's immune functions. To that end, recent studies have already linked the circadian clock to psoriasis, one of the most common immune-mediated skin disorders. Skin also provides opportunities to interrogate the clock regulation of tissue metabolism in the context of stem cells and regeneration. Furthermore, many animal species feature prominent seasonal hair molt cycles, offering an attractive model

  16. Factor structure of functional state of primary school age children

    Directory of Open Access Journals (Sweden)

    Davidenko O.V.

    2011-02-01

    Full Text Available The examination of primary school children to determine the ranking of significant factors that determine the structure of their functional state depending on the level of physical health. It is shown that the main factor in the structure of the functional state of younger schoolchildren in low-and lower-middle level of physical fitness is selected morpho-functional status, which characterizes the functions of the body at rest. For children with average or above average level of physical fitness is a leading factor in physical fitness of schoolchildren.

  17. Skin pattern structure and function of juvenile ages of Chameleo chameleon

    Directory of Open Access Journals (Sweden)

    Yosra A. Fouda

    2017-03-01

    Full Text Available Little is known about the skin structure of juvenile chameleon especially its sensory function of their integumentary structure. Fifteen juvenile Chameleo chameleon are collected from Abu Rawash, Northern area of Giza, Egypt during Summer of 2015. It is belong to the order Squamata, family, Chamaeleonidae. Three ages are used in the present study and categorized according to the morphological criteria of head, abdomen and limb lengths. Dorsal abdominal surfaces are covered with abdominal scales of varying sizes either conical or elliptical-structures, regularly arranged in rows and imbricated with each other. Each scale possessed one cylindrical lenticular epidermal sense organ containing heavy sensillia. Histologically, the scales are characterized by wider conical surfaces and intermingled with another one by hinge region. The epidermal layer of outer scale surface is composed of five-layered stratified squamous epithelium including the stratum germinativum, intermediate zone of stratum spinosum and granulosum, α-keratin layer, β-keratin layer and outer superficial Oberhaütchen. Melanosomes are abundant in the intermediate zone as well as in the peripheral dermal layer underneath stratum germinativum layer. The melanosomes possessed long cellular processes with their content of melanin granules underneath the epidermis. The dermis is composed of upper collagenous and inner compact layer. Semithin sections revealed the presence of fibroblast cells, collagenous fibrils, nerve axons, melanosomes and mast cells in the connective tissue core. Increased immunoreaction of cytokeratin is observed in the epidermal layers of G3; meanwhile, an increased proliferation of epidermal and dermal cells was detected in G1. Transmission electron microscopy exhibited striking formation of dermal sense organs containing neuronal cells of both oligodendrocytes and Schwann cells with myelinated and unmyelinated nerve axons ensheathed externally by thin

  18. Auditory sensitivity and the outer hair cell system in the CBA mouse model of age-related hearing loss.

    Science.gov (United States)

    Frisina, Robert D; Zhu, Xiaoxia

    2010-06-01

    Age-related hearing loss is a highly prevalent sensory disorder, from both the clinical and animal model perspectives. Understanding of the neurophysiologic, structural, and molecular biologic bases of age-related hearing loss will facilitate development of biomedical therapeutic interventions to prevent, slow, or reverse its progression. Thus, increased understanding of relationships between aging of the cochlear (auditory portion of the inner ear) hair cell system and decline in overall hearing ability is necessary. The goal of the present investigation was to test the hypothesis that there would be correlations between physiologic measures of outer hair cell function (otoacoustic emission levels) and hearing sensitivity (auditory brainstem response thresholds), starting in middle age. For the CBA mouse, a useful animal model of age-related hearing loss, it was found that correlations between these two hearing measures occurred only for high sound frequencies in middle age. However, in old age, a correlation was observed across the entire mouse range of hearing. These findings have implications for improved early detection of progression of age-related hearing loss in middle-aged mammals, including mice and humans, and distinguishing peripheral etiologies from central auditory system decline.

  19. Effect of Aging Aircraft Structure on Magnesium Parts

    Science.gov (United States)

    1945-04-01

    structural applications in aircraft, sheet compo - sitions corresponding to Dowmetal FS—1 and Dowmetal J—1 ordinarily are...in the hard—rolled condition. The Dow Chemical Company, Midland, Mich., October 30, 1944. NACA TN So. 979 . TA BIS I

  20. Mitochondrial-associated cell death mechanisms are reset to an embryonic-like state in aged donor-derived iPS cells harboring chromosomal aberrations.

    Science.gov (United States)

    Prigione, Alessandro; Hossini, Amir M; Lichtner, Björn; Serin, Akdes; Fauler, Beatrix; Megges, Matthias; Lurz, Rudi; Lehrach, Hans; Makrantonaki, Eugenia; Zouboulis, Christos C; Adjaye, James

    2011-01-01

    Somatic cells reprogrammed into induced pluripotent stem cells (iPSCs) acquire features of human embryonic stem cells (hESCs) and thus represent a promising source for cellular therapy of debilitating diseases, such as age-related disorders. However, reprogrammed cell lines have been found to harbor various genomic alterations. In addition, we recently discovered that the mitochondrial DNA of human fibroblasts also undergoes random mutational events upon reprogramming. Aged somatic cells might possess high susceptibility to nuclear and mitochondrial genome instability. Hence, concerns over the oncogenic potential of reprogrammed cells due to the lack of genomic integrity may hinder the applicability of iPSC-based therapies for age-associated conditions. Here, we investigated whether aged reprogrammed cells harboring chromosomal abnormalities show resistance to apoptotic cell death or mitochondrial-associated oxidative stress, both hallmarks of cancer transformation. Four iPSC lines were generated from dermal fibroblasts derived from an 84-year-old woman, representing the oldest human donor so far reprogrammed to pluripotency. Despite the presence of karyotype aberrations, all aged-iPSCs were able to differentiate into neurons, re-establish telomerase activity, and reconfigure mitochondrial ultra-structure and functionality to a hESC-like state. Importantly, aged-iPSCs exhibited high sensitivity to drug-induced apoptosis and low levels of oxidative stress and DNA damage, in a similar fashion as iPSCs derived from young donors and hESCs. Thus, the occurrence of chromosomal abnormalities within aged reprogrammed cells might not be sufficient to over-ride the cellular surveillance machinery and induce malignant transformation through the alteration of mitochondrial-associated cell death. Taken together, we unveiled that cellular reprogramming is capable of reversing aging-related features in somatic cells from a very old subject, despite the presence of genomic

  1. Mitochondrial-associated cell death mechanisms are reset to an embryonic-like state in aged donor-derived iPS cells harboring chromosomal aberrations.

    Directory of Open Access Journals (Sweden)

    Alessandro Prigione

    Full Text Available Somatic cells reprogrammed into induced pluripotent stem cells (iPSCs acquire features of human embryonic stem cells (hESCs and thus represent a promising source for cellular therapy of debilitating diseases, such as age-related disorders. However, reprogrammed cell lines have been found to harbor various genomic alterations. In addition, we recently discovered that the mitochondrial DNA of human fibroblasts also undergoes random mutational events upon reprogramming. Aged somatic cells might possess high susceptibility to nuclear and mitochondrial genome instability. Hence, concerns over the oncogenic potential of reprogrammed cells due to the lack of genomic integrity may hinder the applicability of iPSC-based therapies for age-associated conditions. Here, we investigated whether aged reprogrammed cells harboring chromosomal abnormalities show resistance to apoptotic cell death or mitochondrial-associated oxidative stress, both hallmarks of cancer transformation. Four iPSC lines were generated from dermal fibroblasts derived from an 84-year-old woman, representing the oldest human donor so far reprogrammed to pluripotency. Despite the presence of karyotype aberrations, all aged-iPSCs were able to differentiate into neurons, re-establish telomerase activity, and reconfigure mitochondrial ultra-structure and functionality to a hESC-like state. Importantly, aged-iPSCs exhibited high sensitivity to drug-induced apoptosis and low levels of oxidative stress and DNA damage, in a similar fashion as iPSCs derived from young donors and hESCs. Thus, the occurrence of chromosomal abnormalities within aged reprogrammed cells might not be sufficient to over-ride the cellular surveillance machinery and induce malignant transformation through the alteration of mitochondrial-associated cell death. Taken together, we unveiled that cellular reprogramming is capable of reversing aging-related features in somatic cells from a very old subject, despite the presence

  2. Single-cell transcriptomics enters the age of mass production

    NARCIS (Netherlands)

    Junker, Jan Philipp; van Oudenaarden, Alexander

    2015-01-01

    Two publications in the current issue of Cell introduce novel methods for high-throughput single-cell transcriptomics by using droplet microfluidics and sophisticated barcoding schemes for transcriptional profiling of thousands of individual cells.

  3. Aging and perceived event structure as a function of modality.

    Science.gov (United States)

    Magliano, Joseph; Kopp, Kristopher; McNerney, M Windy; Radvansky, Gabriel A; Zacks, Jeffrey M

    2012-01-01

    The majority of research on situation model processing in older adults has focused on narrative texts. Much of this research has shown that many important aspects of constructing a situation model for a text are preserved and may even improve with age. However, narratives need not be text-based, and little is known as to whether these findings generalize to visually-based narratives. The present study assessed the impact of story modality on event segmentation, which is a basic component of event comprehension. Older and younger adults viewed picture stories or read text versions of them and segmented them into events. There was comparable alignment between the segmentation judgments and a theoretically guided analysis of shifts in situational features across modalities for both populations. These results suggest that situation models provide older adults with a stable basis for event comprehension across different modalities of expereinces.

  4. Bacterial cell surface structures in Yersinia enterocolitica.

    Science.gov (United States)

    Białas, Nataniel; Kasperkiewicz, Katarzyna; Radziejewska-Lebrecht, Joanna; Skurnik, Mikael

    2012-06-01

    Yersinia enterocolitica is a widespread member of the family of Enterobacteriaceae that contains both non-virulent and virulent isolates. Pathogenic Y. enterocolitica strains, especially belonging to serotypes O:3, O:5,27, O:8 and O:9 are etiologic agents of yersiniosis in animals and humans. Y. enterocolitica cell surface structures that play a significant role in virulence have been subject to many investigations. These include outer membrane (OM) glycolipids such as lipopolysaccharide (LPS) and enterobacterial common antigen (ECA) and several cell surface adhesion proteins present only in virulent Y. enterocolitica, i.e., Inv, YadA and Ail. While the yadA gene is located on the Yersinia virulence plasmid the Ail, Inv, LPS and ECA are chromosomally encoded. These structures ensure the correct architecture of the OM, provide adhesive properties as well as resistance to antimicrobial peptides and to host innate immune response mechanisms.

  5. Alterations in the expression of atrial calpains in electrical and structural remodeling during aging and atrial fibrillation.

    Science.gov (United States)

    Xu, Guo-Jun; Gan, Tian-Yi; Tang, Bao-Peng; Chen, Zu-Heng; Mahemuti, Ailiman; Jiang, Tao; Song, Jian-Guo; Guo, Xia; Li, Yao-Dong; Zhou, Xian-Hui; Zhang, Yu; Li, Jin-Xin

    2013-11-01

    The aim of this study was to investigate the correlation between the change in the expression of atrial calpains and electrical, molecular and structural remodeling during aging and atrial fibrillation (AF). Adult and aged canines in sinus rhythm (SR) and with persistent AF (induced by rapid atrial pacing) were investigated. A whole-cell patch clamp was used to measure the L-type Ca2+ current (ICa-L) in cells in the left atrium. The mRNA and protein expression of the L-type calcium channel alc subunit (LVDCCa1c) and calpains were measured by quantitative (q)PCR and western blot analysis. Histopathological and ultrastructural changes were analyzed via light and electron microscopy. The quantity of apoptotic myocytes was determined by a terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) assay. In SR groups, atrial cells of the aged canines exhibited a longer action potential (AP) duration to 90% repolarization (APD90), lower AP plateau potential and peak ICa-L current densities (Pcalpain 1 was increased in the adult and the aged groups with AF (Pcalpain 1. The general pathophysiological alterations in normal aged atria may therefore produce a substrate that is conducive to AF.

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

    Science.gov (United States)

    Anguelov, R.; Kojouharov, H.

    2009-10-01

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

  7. Aging and insulin signaling differentially control normal and tumorous germline stem cells.

    Science.gov (United States)

    Kao, Shih-Han; Tseng, Chen-Yuan; Wan, Chih-Ling; Su, Yu-Han; Hsieh, Chang-Che; Pi, Haiwei; Hsu, Hwei-Jan

    2015-02-01

    Aging influences stem cells, but the processes involved remain unclear. Insulin signaling, which controls cellular nutrient sensing and organismal aging, regulates the G2 phase of Drosophila female germ line stem cell (GSC) division cycle in response to diet; furthermore, this signaling pathway is attenuated with age. The role of insulin signaling in GSCs as organisms age, however, is also unclear. Here, we report that aging results in the accumulation of tumorous GSCs, accompanied by a decline in GSC number and proliferation rate. Intriguingly, GSC loss with age is hastened by either accelerating (through eliminating expression of Myt1, a cell cycle inhibitory regulator) or delaying (through mutation of insulin receptor (dinR) GSC division, implying that disrupted cell cycle progression and insulin signaling contribute to age-dependent GSC loss. As flies age, DNA damage accumulates in GSCs, and the S phase of the GSC cell cycle is prolonged. In addition, GSC tumors (which escape the normal stem cell regulatory microenvironment, known as the niche) still respond to aging in a similar manner to normal GSCs, suggesting that niche signals are not required for GSCs to sense or respond to aging. Finally, we show that GSCs from mated and unmated females behave similarly, indicating that female GSC-male communication does not affect GSCs with age. Our results indicate the differential effects of aging and diet mediated by insulin signaling on the stem cell division cycle, highlight the complexity of the regulation of stem cell aging, and describe a link between ovarian cancer and aging.

  8. Influence of aging on the activity of mice Sca-1+CD31− cardiac stem cells

    Science.gov (United States)

    Pu, Shiming; Qin, Liu; Li, Yun; Zhou, Zuping

    2017-01-01

    Therapeutic application of cardiac resident stem/progenitor cells (CSC/CPCs) is limited due to decline of their regenerative potential with donor age. A variety of studies have shown that the cardiac aging was the problem of the stem cells, but little is known about the impact of age on the subgroups CSC/CPCs, the relationship between subgroups CSC/CPCs ageing and age-related dysfunction. Here, we studied Sca-1+CD31− subgroups of CSCs from younger(2~3months) and older(22~24months) age mice, biological differentiation was realized using specific mediums for 14 days to induce cardiomyocyte, smooth muscle cells or endothelial cells and immunostain analysis of differentiated cell resulting were done. Proliferation and cell cycle were measured by flow cytometry assay, then used microarray to dissect variability from younger and older mice. Although the number of CSCs was higher in older mice, the advanced age significantly reduced the differentiation ability into cardiac cell lineages and the proliferation ability. Transcriptional changes in Sca-1+CD31− subgroups of CSCs during aging are related to Vitamin B6 metabolism, circadian rhythm, Tyrosine metabolism, Complement and coagulation cascades. Taking together these results indicate that Cardiac resident stem/progenitor cells have significant differences in their proliferative, pluripotency and gene profiles and those differences are age depending. PMID:27980224

  9. Characterizing structural association alterations within brain networks in normal aging using Gaussian Bayesian networks.

    Science.gov (United States)

    Guo, Xiaojuan; Wang, Yan; Chen, Kewei; Wu, Xia; Zhang, Jiacai; Li, Ke; Jin, Zhen; Yao, Li

    2014-01-01

    Recent multivariate neuroimaging studies have revealed aging-related alterations in brain structural networks. However, the sensory/motor networks such as the auditory, visual and motor networks, have obtained much less attention in normal aging research. In this study, we used Gaussian Bayesian networks (BN), an approach investigating possible inter-regional directed relationship, to characterize aging effects on structural associations between core brain regions within each of these structural sensory/motor networks using volumetric MRI data. We then further examined the discriminability of BN models for the young (N = 109; mean age =22.73 years, range 20-28) and old (N = 82; mean age =74.37 years, range 60-90) groups. The results of the BN modeling demonstrated that structural associations exist between two homotopic brain regions from the left and right hemispheres in each of the three networks. In particular, compared with the young group, the old group had significant connection reductions in each of the three networks and lesser connection numbers in the visual network. Moreover, it was found that the aging-related BN models could distinguish the young and old individuals with 90.05, 73.82, and 88.48% accuracy for the auditory, visual, and motor networks, respectively. Our findings suggest that BN models can be used to investigate the normal aging process with reliable statistical power. Moreover, these differences in structural inter-regional interactions may help elucidate the neuronal mechanism of anatomical changes in normal aging.

  10. Alloimmunization is associated with older age of transfused red blood cells in sickle cell disease.

    Science.gov (United States)

    Desai, Payal C; Deal, Allison M; Pfaff, Emily R; Qaqish, Bahjat; Hebden, Leyna M; Park, Yara A; Ataga, Kenneth I

    2015-08-01

    Red blood cell (RBC) alloimmunization is a significant clinical complication of sickle cell disease (SCD). It can lead to difficulty with cross-matching for future transfusions and may sometimes trigger life-threatening delayed hemolytic transfusion reactions. We conducted a retrospective study to explore the association of clinical complications and age of RBC with alloimmunization in patients with SCD followed at a single institution from 2005 to 2012. One hundred and sixty six patients with a total of 488 RBC transfusions were evaluated. Nineteen patients (11%) developed new alloantibodies following blood transfusions during the period of review. The median age of RBC units was 20 days (interquartile range: 14-27 days). RBC antibody formation was significantly associated with the age of RBC units (P = 0.002), with a hazard ratio of 3.5 (95% CI: 1.71-7.11) for a RBC unit that was 7 days old and 9.8 (95% CI: 2.66-35.97) for a unit that was 35 days old, 28 days after the blood transfusion. No association was observed between RBC alloimmunization and acute vaso-occlusive complications. Although increased echocardiography-derived tricuspid regurgitant jet velocity (TRV) was associated with the presence of RBC alloantibodies (P = 0.02), TRV was not significantly associated with alloimmunization when adjusted for patient age and number of transfused RBC units. Our study suggests that RBC antibody formation is significantly associated with older age of RBCs at the time of transfusion. Prospective studies in patients with SCD are required to confirm this finding.

  11. Direct measurement of riverine particulate organic carbon age structure

    Science.gov (United States)

    Rosenheim, Brad E.; Galy, Valier

    2012-10-01

    Carbon cycling studies focusing on transport and transformation of terrigenous carbon sources toward marine sedimentary sinks necessitate separation of particulate organic carbon (OC) derived from many different sources and integrated by river systems. Much progress has been made on isolating and characterizing young biologically-formed OC that is still chemically intact, however quantification and characterization of old, refractory rock-bound OC has remained troublesome. Quantification of both endmembers of riverine OC is important to constrain exchanges linking biologic and geologic carbon cycles and regulating atmospheric CO2 and O2. Here, we constrain petrogenic OC proportions in suspended sediment from the headwaters of the Ganges River in Nepal through direct measurement using ramped pyrolysis radiocarbon analysis. The unique results apportion the biospheric and petrogenic fractions of bulk particulate OC and characterize biospheric OC residence time. Compared to the same treatment of POC from the lower Mississippi-Atchafalaya River system, contrast in age spectra of the Ganges tributary samples illustrates the difference between small mountainous river systems and large integrative ones in terms of the global carbon cycle.

  12. Population structure age of Paraná state between 1970 and 2010

    Directory of Open Access Journals (Sweden)

    Eduardo de Pintor

    2014-06-01

    Full Text Available The theory of demographic transition began with an effort of Frank Notestein (1945 to understand the demographic changes that were occurring in Western Europe since the late nineteenth century. The demographic transition is the transition between two scenarios of population growth, which changes the age structure of the population. The aim of the article is to discuss the evolution of population structure age of Paraná state between 1970 and 2010. The changes in the age structure of the Paraná indicate a reduction in the share of young population and increasing aging population, an increase in the relative weight of the elderly population. Public policies on education, health, social security and labor market should consider the current change in the age structure. Thus, the aim of this study was to analyze the change in the age structure of the population of the state of Paraná. For this we used data Censuses of the Brazilian Institute of Geography and Statistics (IBGE on the age distribution of urban and rural Paraná and its Mesoregions. It was concluded that the change in structure occurs group widespread in all Mesoregions state. However, it occurs unevenly between urban and rural population.

  13. Anti-aging effects of vitamin C on human pluripotent stem cell-derived cardiomyocytes.

    Science.gov (United States)

    Kim, Yoon Young; Ku, Seung-Yup; Huh, Yul; Liu, Hung-Ching; Kim, Seok Hyun; Choi, Young Min; Moon, Shin Yong

    2013-10-01

    Human pluripotent stem cells (hPSCs) have arisen as a source of cells for biomedical research due to their developmental potential. Stem cells possess the promise of providing clinicians with novel treatments for disease as well as allowing researchers to generate human-specific cellular metabolism models. Aging is a natural process of living organisms, yet aging in human heart cells is difficult to study due to the ethical considerations regarding human experimentation as well as a current lack of alternative experimental models. hPSC-derived cardiomyocytes (CMs) bear a resemblance to human cardiac cells and thus hPSC-derived CMs are considered to be a viable alternative model to study human heart cell aging. In this study, we used hPSC-derived CMs as an in vitro aging model. We generated cardiomyocytes from hPSCs and demonstrated the process of aging in both human embryonic stem cell (hESC)- and induced pluripotent stem cell (hiPSC)-derived CMs. Aging in hESC-derived CMs correlated with reduced membrane potential in mitochondria, the accumulation of lipofuscin, a slower beating pattern, and the downregulation of human telomerase RNA (hTR) and cell cycle regulating genes. Interestingly, the expression of hTR in hiPSC-derived CMs was not significantly downregulated, unlike in hESC-derived CMs. In order to delay aging, vitamin C was added to the cultured CMs. When cells were treated with 100 μM of vitamin C for 48 h, anti-aging effects, specifically on the expression of telomere-related genes and their functionality in aging cells, were observed. Taken together, these results suggest that hPSC-derived CMs can be used as a unique human cardiomyocyte aging model in vitro and that vitamin C shows anti-aging effects in this model.

  14. AGE-modified basement membrane cooperates with Endo180 to promote epithelial cell invasiveness and decrease prostate cancer survival

    DEFF Research Database (Denmark)

    Rodriguez-Teja, Mercedes; Gronau, Julian H; Breit, Claudia

    2015-01-01

    Biomechanical strain imposed by age-related thickening of the basal lamina and augmented tissue stiffness in the prostate gland coincides with increased cancer risk. Here we hypothesized that the structural alterations in the basal lamina associated with age can induce mechanotransduction pathways...... in prostate epithelial cells (PECs) to promote invasiveness and cancer progression. To demonstrate this, we developed a 3D model of PEC acini in which thickening and stiffening of basal lamina matrix was induced by advanced glycation end-product (AGE)-dependent non-enzymatic crosslinking of its major......(Δ) (Ex2-6/) (Δ) (Ex2-6) mice, with constitutively exposed CTLD2 and decreased survival of men with early (non-invasive) prostate cancer with high epithelial Endo180 expression and levels of AGE. These findings indicate that AGE-dependent modification of the basal lamina induces invasive behaviour...

  15. Increased centrosome amplification in aged stem cells of the Drosophila midgut

    Energy Technology Data Exchange (ETDEWEB)

    Park, Joung-Sun; Pyo, Jung-Hoon; Na, Hyun-Jin; Jeon, Ho-Jun; Kim, Young-Shin [Department of Molecular Biology, Pusan National University, Busan 609-735 (Korea, Republic of); Arking, Robert, E-mail: aa2210@wayne.edu [Department of Biological Sciences, Wayne State University, Detroit, MI 48202 (United States); Yoo, Mi-Ae, E-mail: mayoo@pusan.ac.kr [Department of Molecular Biology, Pusan National University, Busan 609-735 (Korea, Republic of)

    2014-07-25

    Highlights: • Increased centrosome amplification in ISCs of aged Drosophila midguts. • Increased centrosome amplification in ISCs of oxidative stressed Drosophila midguts. • Increased centrosome amplification in ISCs by overexpression of PVR, EGFR, and AKT. • Supernumerary centrosomes can be responsible for abnormal ISC polyploid cells. • Supernumerary centrosomes can be a useful marker for aging stem cells. - Abstract: Age-related changes in long-lived tissue-resident stem cells may be tightly linked to aging and age-related diseases such as cancer. Centrosomes play key roles in cell proliferation, differentiation and migration. Supernumerary centrosomes are known to be an early event in tumorigenesis and senescence. However, the age-related changes of centrosome duplication in tissue-resident stem cells in vivo remain unknown. Here, using anti-γ-tubulin and anti-PH3, we analyzed mitotic intestinal stem cells with supernumerary centrosomes in the adult Drosophila midgut, which may be a versatile model system for stem cell biology. The results showed increased centrosome amplification in intestinal stem cells of aged and oxidatively stressed Drosophila midguts. Increased centrosome amplification was detected by overexpression of PVR, EGFR, and AKT in intestinal stem cells/enteroblasts, known to mimic age-related changes including hyperproliferation of intestinal stem cells and hyperplasia in the midgut. Our data show the first direct evidence for the age-related increase of centrosome amplification in intestinal stem cells and suggest that the Drosophila midgut is an excellent model for studying molecular mechanisms underlying centrosome amplification in aging adult stem cells in vivo.

  16. Biological character of human adipose-derived adult stem cells and influence of donor age on cell replication in culture.

    Science.gov (United States)

    Lei, Lei; Liao, WeiMing; Sheng, PuYi; Fu, Ming; He, AiShan; Huang, Gang

    2007-06-01

    To investigate the biological character of human adipose-derived adult stem cells (hADAS cells) when cultured in vitro and the relationship between hADAS cell's replication activity and the donor's age factor, and to assess the stem cells as a new source for tissue engineering. hADAS cells are isolated from human adipose tissue of different age groups (from adolescents to olds: 61 years old groups). The protein markers (CD29, CD34, CD44, CD45, CD49d, HLA-DR, CD106) of hADAS cells were detected by flow cytometry (FCM) to identify the stem cell, and the cell cycle was examined for P20 hADAS cells to evaluate the safety of the subculture in vitro. The generative activity of hADAS cells in different age groups was also examined by MTT method. The formula "TD = t x log2/logNt - logN0" was used to get the time doubling (TD) of the cells. The results showed that the cells kept heredity stabilization by chromosome analysis for at least 20 passages. The TD of these cells increased progressively by ageing, and the TD of the 61 years old group (statistical analysis of variance (ANOVA), P=0.002, PhADAS cells replication activity was found in the younger donators, and they represent novel and valuable seed cells for studies of tissue engineering.

  17. Impact of aging and material structure on CANDU plant performance

    Energy Technology Data Exchange (ETDEWEB)

    Nadeau, E.; Ballyk, J.; Ghalavand, N. [Candu Energy Inc., Mississauga, Ontario (Canada)

    2011-07-01

    In-service behaviour of pressure tubes is a key factor in the assessment of safety margins during plant operation. Pressure tube deformation (diametral expansion) affects fuel bundle dry out characteristics resulting in reduced margin to trip for some events. Pressure tube aging mechanisms also erode design margins on fuel channels or interfacing reactor components. The degradation mechanisms of interest are primarily deformation, loss of fracture resistance and hydrogen ingress. CANDU (CANada Deuterium Uranium, a registered trademark of the Atomic Energy of Canada Limited used under exclusive licence by Candu Energy Inc.) owners and operators need to maximize plant capacity factor and meet or exceed the reactor design life targets while maintaining safety margins. The degradation of pressure tube material and geometry are characterized through a program of inspection, material surveillance and assessment and need to be managed to optimize plant performance. Candu is improving pressure tubes installed in new build and life extension projects. Improvements include changes designed to reduce or mitigate the impact of pressure tube elongation and diametral expansion rates, improvement of pressure tube fracture properties, and reduction of the implications of hydrogen ingress. In addition, Candu provides an extensive array of engineering services designed to assess the condition of pressure tubes and address the impact of pressure tube degradation on safety margins and plant performance. These services include periodic and in-service inspection and material surveillance of pressure tubes and deterministic and probabilistic assessment of pressure tube fitness for service to applicable standards. Activities designed to mitigate the impact of pressure tube deformation on safety margins include steam generator cleaning, which improves trip margins, and trip design assessment to optimize reactor trip set points restoring safety and operating margins. This paper provides an

  18. Autophagic deficiency is related to steroidogenic decline in aged rat Leydig cells

    Institute of Scientific and Technical Information of China (English)

    Wei-Ren Li; Zhe-Zhu Gao; Zhong-Cheng Xin; Liang Chen; Zhi-Jie Chang; Hua Xin; Tao Liu; Yan-Quan Zhang; Guang-Yong Li; Feng Zhou; Yan-Qing Gong

    2011-01-01

    Late-onset hypogonadism (LOH) is closely related to secondary androgen deficiency in aged males,but the mechanism remains unclear.In this study,we found that reduced testosterone production in aged rat Leydig cells is associated with decreased autophagic activity.Primary rat Leydig cells and the TM3 mouse Leydig cell line were used to study the effect of autophagic deficiency on Leydig cell testosterone production.In Leydig cells from young and aged rats,treatment with wortmannin,an autophagy inhibitor,inhibited luteinising hormone (LH)-stimulated steroidogenic acute regulatory (StAR) protein expression and decreased testosterone production.In contrast,treatment with rapamycin,an autophagy activator,enhanced LH-stimulated steroidogenesis in Leydig cells from aged,but not young,rats.Intracellular reactive oxygen species (ROS) levels were increased in both young and aged Leydig cells treated with wortmannin but decreased only in aged Leydig cells treated with rapamycin.Furthermore,an increased level of ROS,induced by H2O2,resulted in LH-stimulated steroidogenic inhibition.Finally,knockdown of Beclin 1 decreased LH-stimulated StAR expression and testosterone production in TM3 mouse Leydig cells,which were associated with increased intracellular ROS level.These results suggested that autophagic deficiency is related to steroidogenic decline in aged rat Leydig cells,which might be influenced by intracellular ROS levels.

  19. Age-related molecular genetic changes of murine bone marrow mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Webster Keith A

    2010-04-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSC are pluripotent cells, present in the bone marrow and other tissues that can differentiate into cells of all germ layers and may be involved in tissue maintenance and repair in adult organisms. Because of their plasticity and accessibility these cells are also prime candidates for regenerative medicine. The contribution of stem cell aging to organismal aging is under debate and one theory is that reparative processes deteriorate as a consequence of stem cell aging and/or decrease in number. Age has been linked with changes in osteogenic and adipogenic potential of MSCs. Results Here we report on changes in global gene expression of cultured MSCs isolated from the bone marrow of mice at ages 2, 8, and 26-months. Microarray analyses revealed significant changes in the expression of more than 8000 genes with stage-specific changes of multiple differentiation, cell cycle and growth factor genes. Key markers of adipogenesis including lipoprotein lipase, FABP4, and Itm2a displayed age-dependent declines. Expression of the master cell cycle regulators p53 and p21 and growth factors HGF and VEGF also declined significantly at 26 months. These changes were evident despite multiple cell divisions in vitro after bone marrow isolation. Conclusions The results suggest that MSCs are subject to molecular genetic changes during aging that are conserved during passage in culture. These changes may affect the physiological functions and the potential of autologous MSCs for stem cell therapy.

  20. Doublecortin-expressing cells persist in the associative cerebral cortex and amygdala in aged nonhuman primates

    Directory of Open Access Journals (Sweden)

    Xue-mei Zhang

    2009-10-01

    Full Text Available A novel population of cells that express typical immature neuronal markers including doublecortin (DCX+ has been recently identified throughout the adult cerebral cortex of relatively large mammals (guinea pig, rabbit, cat, monkey and human. These cells are more common in the associative relative to primary cortical areas and appear to develop into interneurons including type II nitrinergic neurons. Here we further describe these cells in the cerebral cortex and amygdala, in comparison with DCX+ cells in the hippocampal dentate gyrus, in 3 age groups of rhesus monkeys: young adult (12.3±0.2 yrs, n=3, mid-age (21.2±1.9 yrs, n=3 and aged (31.3±1.8 yrs, n=4. DCX+ cells with a heterogeneous morphology persisted in layers II/III primarily over the associative cortex and amygdala in all groups (including in two old animals with cerebral amyloid pathology, showing a parallel decline in cell density with age across regions. In contrast to the cortex and amygdala, DCX+ cells in the subgranular zone diminished in the mid-age and aged groups. DCX+ cortical cells might arrange as long tangential migratory chains in the mid-age and aged animals, with apparently distorted cell clusters seen in the aged group. Cortical DCX+ cells colocalized commonly with polysialylated neural cell adhesion molecule (PSA-NCAM and partially with neuron-specific nuclear protein (NeuN and γ-aminobutyric acid (GABA, suggesting a potential differentiation of these cells into interneuron phenotype. These data suggest a life-long role for immature interneuron-like cells in the associative cerebral cortex and amygdala in nonhuman primates.

  1. The Effect of Polybutadiene Polymer on Cell Aging In Vitro.

    Science.gov (United States)

    Liu, Ying; Collazo, Lourdes; Rafailovich, Miriam; Sokolov, Jonathan

    2006-03-01

    Cell experimentation often undergoes several weeks of culturing. The most common problem that scientists face is the variability of cell behavior due to subculturing. Most cells have a limited lifespan in vitro, changing their cell characteristic after just a few passages. Here we focus on the changes in cell function with passage. We used human CRF31 dermal fibroblasts initially cultured from lower passages (P11) to higher passages (P20) at a density of 5000/cm2. We first generated a series of cell growth curves for the different passages. We observed that as cell passage number increased, cell proliferation decreased significantly. Western Blot analysis indicated that the composition of the extracellular matrix proteins changed with increasing passage. The effect of these changes on migration and actin production will be presented.

  2. Aging and Immortality in a Cell Proliferation Model

    CERN Document Server

    Antal, T; Trugman, S A; Redner, S

    2007-01-01

    We investigate a model of cell division in which the length of telomeres within the cell regulate their proliferative potential. At each cell division the ends of linear chromosomes change and a cell becomes senescent when one or more of its telomeres become shorter than a critical length. In addition to this systematic shortening, exchange of telomere DNA between the two daughter cells can occur at each cell division. We map this telomere dynamics onto a biased branching diffusion process with an absorbing boundary condition whenever any telomere reaches the critical length. As the relative effects of telomere shortening and cell division are varied, there is a phase transition between finite lifetime and infinite proliferation of the cell population. Using simple first-passage ideas, we quantify the nature of this transition.

  3. Association of structural global brain network properties with intelligence in normal aging.

    Directory of Open Access Journals (Sweden)

    Florian U Fischer

    Full Text Available Higher general intelligence attenuates age-associated cognitive decline and the risk of dementia. Thus, intelligence has been associated with cognitive reserve or resilience in normal aging. Neurophysiologically, intelligence is considered as a complex capacity that is dependent on a global cognitive network rather than isolated brain areas. An association of structural as well as functional brain network characteristics with intelligence has already been reported in young adults. We investigated the relationship between global structural brain network properties, general intelligence and age in a group of 43 cognitively healthy elderly, age 60-85 years. Individuals were assessed cross-sectionally using Wechsler Adult Intelligence Scale-Revised (WAIS-R and diffusion-tensor imaging. Structural brain networks were reconstructed individually using deterministic tractography, global network properties (global efficiency, mean shortest path length, and clustering coefficient were determined by graph theory and correlated to intelligence scores within both age groups. Network properties were significantly correlated to age, whereas no significant correlation to WAIS-R was observed. However, in a subgroup of 15 individuals aged 75 and above, the network properties were significantly correlated to WAIS-R. Our findings suggest that general intelligence and global properties of structural brain networks may not be generally associated in cognitively healthy elderly. However, we provide first evidence of an association between global structural brain network properties and general intelligence in advanced elderly. Intelligence might be affected by age-associated network deterioration only if a certain threshold of structural degeneration is exceeded. Thus, age-associated brain structural changes seem to be partially compensated by the network and the range of this compensation might be a surrogate of cognitive reserve or brain resilience.

  4. Association of structural global brain network properties with intelligence in normal aging.

    Science.gov (United States)

    Fischer, Florian U; Wolf, Dominik; Scheurich, Armin; Fellgiebel, Andreas

    2014-01-01

    Higher general intelligence attenuates age-associated cognitive decline and the risk of dementia. Thus, intelligence has been associated with cognitive reserve or resilience in normal aging. Neurophysiologically, intelligence is considered as a complex capacity that is dependent on a global cognitive network rather than isolated brain areas. An association of structural as well as functional brain network characteristics with intelligence has already been reported in young adults. We investigated the relationship between global structural brain network properties, general intelligence and age in a group of 43 cognitively healthy elderly, age 60-85 years. Individuals were assessed cross-sectionally using Wechsler Adult Intelligence Scale-Revised (WAIS-R) and diffusion-tensor imaging. Structural brain networks were reconstructed individually using deterministic tractography, global network properties (global efficiency, mean shortest path length, and clustering coefficient) were determined by graph theory and correlated to intelligence scores within both age groups. Network properties were significantly correlated to age, whereas no significant correlation to WAIS-R was observed. However, in a subgroup of 15 individuals aged 75 and above, the network properties were significantly correlated to WAIS-R. Our findings suggest that general intelligence and global properties of structural brain networks may not be generally associated in cognitively healthy elderly. However, we provide first evidence of an association between global structural brain network properties and general intelligence in advanced elderly. Intelligence might be affected by age-associated network deterioration only if a certain threshold of structural degeneration is exceeded. Thus, age-associated brain structural changes seem to be partially compensated by the network and the range of this compensation might be a surrogate of cognitive reserve or brain resilience.

  5. Structural Aging Program to evaluate continued performance of safety-related concrete structures in nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Naus, D.J.; Oland, C.B. [Oak Ridge National Lab., TN (United States); Ellingwood, B.R. [Johns Hopkins Univ., Baltimore, MD (United States)

    1994-03-01

    This report discusses the Structural Aging (SAG) Program which is being conducted at the Oak Ridge National Laboratory (ORNL) for the United States Nuclear Regulatory commission (USNRC). The SAG Program is addressing the aging management of safety-related concrete structures in nuclear power plants for the purpose of providing improved technical bases for their continued service. The program is organized into three technical tasks: Materials Property Data Base, Structural Component Assessment/Repair Technologies, and Quantitative Methodology for continued Service Determinations. Objectives and a summary of recent accomplishments under each of these tasks are presented.

  6. Characteristics and Behavior of Cycled Aged Lithium Ion Cells

    Science.gov (United States)

    2010-01-01

    service cycle and provide the cornerstone for safety analysis. 18650 Cells with representative chemistry of cells contained in current Army procured...their relevance to this effort warrants inclusion. 1-3 EXPERIMENTAL Representative 18650 cells were cycled at different rates and environmental...conditions. The 18650 chemistry used in this effort is a LiCoO2 lithium ion electrochemical cell. The bulk of this effort was conducted with 1.5 Amp-hr

  7. Factor Structure of Attention Deficit Hyperactivity Disorder Symptoms for Children Age 3 to 5 Years

    Science.gov (United States)

    McGoey, Kara E.; Schreiber, James; Venesky, Lindsey; Westwood, Wendy; McGuirk, Lindsay; Schaffner, Kristen

    2015-01-01

    The diagnosis of attention deficit hyperactivity disorder (ADHD) distinguishes two dimensions of symptoms, inattention and hyperactivity-impulsivity for ages 3 to adulthood. Currently, no separate classification for preschool-age children exists, whereas preliminary research suggests that the two-factor structure of ADHD may not match the…

  8. Structural hippocampal network alterations during healthy aging: A multi-modal MRI study

    Directory of Open Access Journals (Sweden)

    Amandine ePelletier

    2013-12-01

    Full Text Available While hippocampal atrophy has been described during healthy aging, few studies have examined its relationship with the integrity of White Matter (WM connecting tracts of the limbic system. This investigation examined WM structural damage specifically related to hippocampal atrophy in healthy aging subjects (n=129, using morphological MRI to assess hippocampal volume and Diffusion Tensor Imaging (DTI to assess WM integrity. Subjects with Mild Cognitive Impairment (MCI or dementia were excluded from the analysis. In our sample, increasing age was significantly associated with reduced hippocampal volume and reduced Fractional Anisotropy (FA at the level of the fornix and the cingulum bundle. The findings also demonstrate that hippocampal atrophy was specifically associated with reduced FA of the fornix bundle, but it was not related to alteration of the cingulum bundle. Our results indicate that the relationship between hippocampal atrophy and fornix FA values is not due to an independent effect of age on both structures. A recursive regression procedure was applied to evaluate sequential relationships between the alterations of these two brain structures. When both hippocampal atrophy and fornix FA values were included in the same model to predict age, fornix FA values remained significant whereas hippocampal atrophy was no longer significantly associated with age. According to this latter finding, hippocampal atrophy in healthy aging could be mediated by a loss of fornix connections. Structural alterations of this part of the limbic system, which have been associated with neurodegeneration in Alzheimer’s disease, result at least in part from the aging process.

  9. Existence and Uniqueness of Endemic States for the Age-structured MSEIR Epidemic Model

    Institute of Scientific and Technical Information of China (English)

    Xue-zhi Li; Geni Gupur; Guang-tian Zhu

    2002-01-01

    The existence and uniqueness of positive steady states for the age-structured MSEIR epidemic model with age-dependent transmission coefficient is considered. Threshold results for the existence of endemic states are established; under certain conditions, uniqueness is also shown.

  10. Structural evidence that human acetylcholinesterase inhibited by tabun ages through O-dealkylation.

    Science.gov (United States)

    Carletti, Eugénie; Colletier, Jacques-Philippe; Dupeux, Florine; Trovaslet, Marie; Masson, Patrick; Nachon, Florian

    2010-05-27

    Tabun is a warfare agent that inhibits human acetylcholinesterase (hAChE) by rapid phosphylation of the catalytic serine. A time-dependent reaction occurs on the tabun adduct, leading to an "aged" enzyme, resistant to oxime reactivators. The aging reaction may proceed via either dealkylation or deamidation, depending on the stereochemistry of the phosphoramidyl adduct. We solved the X-ray structure of aged tabun-hAChE complexed with fasciculin II, and we show that aging proceeds through O-dealkylation, in agreement with the aging mechanism that we determined for tabun-inhibited human butyrylcholinesterase and mouse acetylcholinesterase. Noteworthy, aging and binding of fasciculin II lead to an improved thermostability, resulting from additional stabilizing interactions between the two subdomains that face each other across the active site gorge. This first structure of hAChE inhibited by a nerve agent provides structural insight into the inhibition and aging mechanisms and a structural template for the design of molecules capable of reactivating aged hAChE.

  11. Aging disturbs the balance between effector and regulatory CD4+T cells

    NARCIS (Netherlands)

    van der Geest, Kornelis S. M.; Abdulahad, Wayel H.; Tete, Sarah M.; Lorencetti, Pedro G.; Horst, Gerda; Bos, Nicolaas A.; Kroesen, Bart-Jan; Brouwer, Elisabeth; Boots, Annemieke M. H.

    2014-01-01

    Healthy aging requires an optimal balance between pro-inflammatory and anti-inflammatory immune responses. Although CD4+ T cells play an essential role in many immune responses, few studies have directly assessed the effect of aging on the balance between effector T (Teff) cells and regulatory T (Tr

  12. Regenerative and reparative effects of human chorion-derived stem cell conditioned medium on photo-aged epidermal cells.

    Science.gov (United States)

    Li, Qiankun; Chen, Yan; Ma, Kui; Zhao, Along; Zhang, Cuiping; Fu, Xiaobing

    2016-01-01

    Epidermal cells are an important regenerative source for skin wound healing. Aged epidermal cells have a low ability to renew themselves and repair skin injury. Ultraviolet (UV) radiation, particularly UVB, can cause photo-aging of the skin by suppressing the viability of human epidermal cells. A chorion-derived stem cell conditioned medium (CDSC-CNM) is thought to have regenerative properties. This study aimed to determine the regenerative effects of CDSC-CNM on UVB-induced photo-aged epidermal cells. Epidermal cells were passaged four times and irradiated with quantitative UVB, and non-irradiated cells served as a control group. Cells were then treated with different concentrations of CDSC-CNM. Compared to the non-irradiated group, the proliferation rates and migration rates of UVB-induced photo-aged epidermal cells significantly decreased (p photo-aged epidermal cells significantly improved their viability, and their ROS generation and DNA damage decreased. The secretory factors in CDSC-CNM, including epidermal growth factor (EGF), transforming growth factor-β (TGF-β), interleukin (IL)-6, and IL-8 and the related signaling pathway protein levels, increased compared to the control medium (CM). The potential regenerative and reparative effects of CDSC-CNM indicate that it may be a candidate material for the treatment of prematurely aged skin. The functions of the secretory factors and the mechanisms of CDSC-CNM therapy deserve further attention.

  13. Transplanted adipose-derived stem cells delay D-galactose-induced aging in rats

    Institute of Scientific and Technical Information of China (English)

    Chun Yang; Ou Sha; Jingxing Dai; Lin Yuan; Dongfei Li; Zhongqiu Wen; Huiying Yang; Meichun Yu; Hui Tao; Rongmei Qu; Yikuan Du; Yong Huang

    2011-01-01

    To investigate the effects of allogeneically transplanted, adipose-derived stem cells in aging rats, in the present study, we established a rat model of subacute aging using continuous subcutaneous injections of D-galactose. Two weeks after the adipose-derived stem cells transplantations, serum superoxide dismutase activity was significantly increased, malondialdehyde content was significantly reduced, hippocampal neuronal degeneration was ameliorated, the apoptotic index of hippocampal neurons was decreased, and learning and memory function was significantly improved in the aging rats. These results indicate that allogeneic transplantation of adipose-derived stem cells may effectively delay D-galactose-induced aging.

  14. AGING OF HUMAN MATURE ERYTHROCYTES IS LIKE A PROCESS OF APOPTOSIS IN ENUCLEATED CELL

    Institute of Scientific and Technical Information of China (English)

    潘华珍; 冯立明; 卢红; 许彩民; 张平诚; 张之南

    1998-01-01

    Apoptosis of nucleated cells is well known, but bow about the unnucleated cells is still not elucidated.In the present paper, the morphological and biochemical features of the aged eryshrocytes were observed and compared with the characteristic events of apoptosis. Membrane of aged erythrocytes tends to shrink,protrude, from vesicle and lose lipid asymmetry. Aged erythrocytes were removed by phagocytosis. Both of the events are very similar to the apoptotic nucleated cells. The authors suggested that aging of erythrocytes is also a process of apoptosis.

  15. Stem Cell-Specific Mechanisms Ensure Genomic Fidelity within HSCs and upon Aging of HSCs

    Directory of Open Access Journals (Sweden)

    Bettina M. Moehrle

    2015-12-01

    Full Text Available Whether aged hematopoietic stem and progenitor cells (HSPCs have impaired DNA damage repair is controversial. Using a combination of DNA mutation indicator assays, we observe a 2- to 3-fold increase in the number of DNA mutations in the hematopoietic system upon aging. Young and aged hematopoietic stem cells (HSCs and hematopoietic progenitor cells (HPCs do not show an increase in mutation upon irradiation-induced DNA damage repair, and young and aged HSPCs respond very similarly to DNA damage with respect to cell-cycle checkpoint activation and apoptosis. Both young and aged HSPCs show impaired activation of the DNA-damage-induced G1-S checkpoint. Induction of chronic DNA double-strand breaks by zinc-finger nucleases suggests that HSPCs undergo apoptosis rather than faulty repair. These data reveal a protective mechanism in both the young and aged hematopoietic system against accumulation of mutations in response to DNA damage.

  16. Compact attractors for time-periodic age-structured population models

    Directory of Open Access Journals (Sweden)

    Pierre Magal

    2001-10-01

    Full Text Available In this paper we investigate the existence of compact attractors for time-periodic age-structured models. So doing we investigate the eventual compactness of a class of abstract non-autonomous semiflow (non necessarily periodic. We apply this result to non-autonomous age-structured models. In the time periodic case, we obtain the existence of a periodic family of compact subsets that is invariant by the semiflow, and attract the solutions of the system.

  17. Age-related changes of normal adult brain structure: analysed with diffusion tensor imaging

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yun-ting; ZHANG Chun-yan; ZHANG Jing; LI Wei

    2005-01-01

    Background It is known that the brain structure changes with normal aging. The objective of this study was to quantify the anisotropy and average diffusion coefficient (DCavg) of the brain in normal adults to demonstrate the microstructure changes of brain with aging.Methods One hundred and six normal adults were examined with diffusion tensor imaging (DTI). The fractional anisotropy (FA), 1-volume ratio (1-VR), relative anisotropy (RA) and average diffusion coefficient (DCavg) of different anatomic sites of brain were measured, correlated with age and compared among three broad age groups.Results Except in lentiform nucleus, the anisotropy increased and DCavg decreased with aging. Both anisotropy and DCavg of lentiform nucleus increased with aging. The normal reference values of DTI parameters of normal Chinese adult in major anatomic sites were acquired. Conclusions DTI data obtained noninvasively can reflect the microstructural changes with aging. The normal reference values acquired can serve as reference standards in differentiation of brain white matter diseases.

  18. Direct volume rendering methods for cell structures.

    Science.gov (United States)

    Martišek, Dalibor; Martišek, Karel

    2012-01-01

    The study of the complicated architecture of cell space structures is an important problem in biology and medical research. Optical cuts of cells produced by confocal microscopes enable two-dimensional (2D) and three-dimensional (3D) reconstructions of observed cells. This paper discuses new possibilities for direct volume rendering of these data. We often encounter 16 or more bit images in confocal microscopy of cells. Most of the information contained in these images is unsubstantial for the human vision. Therefore, it is necessary to use mathematical algorithms for visualization of such images. Present software tools as OpenGL or DirectX run quickly in graphic station with special graphic cards, run very unsatisfactory on PC without these cards and outputs are usually poor for real data. These tools are black boxes for a common user and make it impossible to correct and improve them. With the method proposed, more parameters of the environment can be set, making it possible to apply 3D filters to set the output image sharpness in relation to the noise. The quality of the output is incomparable to the earlier described methods and is worth increasing the computing time. We would like to offer mathematical methods of 3D scalar data visualization describing new algorithms that run on standard PCs very well.

  19. Structural correlates of rotavirus cell entry.

    Directory of Open Access Journals (Sweden)

    Aliaa H Abdelhakim

    2014-09-01

    Full Text Available Cell entry by non-enveloped viruses requires translocation into the cytosol of a macromolecular complex--for double-strand RNA viruses, a complete subviral particle. We have used live-cell fluorescence imaging to follow rotavirus entry and penetration into the cytosol of its ∼ 700 Å inner capsid particle ("double-layered particle", DLP. We label with distinct fluorescent tags the DLP and each of the two outer-layer proteins and track the fates of each species as the particles bind and enter BSC-1 cells. Virions attach to their glycolipid receptors in the host cell membrane and rapidly become inaccessible to externally added agents; most particles that release their DLP into the cytosol have done so by ∼ 10 minutes, as detected by rapid diffusional motion of the DLP away from residual outer-layer proteins. Electron microscopy shows images of particles at various stages of engulfment into tightly fitting membrane invaginations, consistent with the interpretation that rotavirus particles drive their own uptake. Electron cryotomography of membrane-bound virions also shows closely wrapped membrane. Combined with high resolution structural information about the viral components, these observations suggest a molecular model for membrane disruption and DLP penetration.

  20. [Structure and function of fungal cell wall].

    Science.gov (United States)

    Ohno, Naohito

    2008-12-01

    Cell wall glycans of fungi/yeasts are reviewed. Fungi/yeasts produce various kinds of polysaccharides. As part of the cell wall they are interlinked with other components forming a huge network. The insolubility and complex with multiple components makes the research very tough. Studies on beta-glucan have been performed from various views, such as chemistry, conformation, solubility, tissue distribution and metabolism, biological activity, clinical application, receptor, biosynthesis, and antibody. Studies on mannan focus on immunotoxicity, such as anaphylactoid reaction and coronary arteritis induction. alpha-glucan, chitin, and capsular polysaccharide were also mentioned in relation to structure and genes. Compared with human and animal polysaccharides, fungi/yeasts polysaccharides have very characteristic properties.

  1. Hyperhomocysteinemia disrupts retinal pigment epithelial structure and function with features of age-related macular degeneration.

    Science.gov (United States)

    Ibrahim, Ahmed S; Mander, Suchreet; Hussein, Khaled A; Elsherbiny, Nehal M; Smith, Sylvia B; Al-Shabrawey, Mohamed; Tawfik, Amany

    2016-02-23

    The disruption of retinal pigment epithelial (RPE) function and the degeneration of photoreceptors are cardinal features of age related macular degeneration (AMD); however there are still gaps in our understanding of underlying biological processes. Excess homocysteine (Hcy) has been reported to be elevated in plasma of patients with AMD. This study aimed to evaluate the direct effect of hyperhomocysteinemia (HHcy) on structure and function of RPE. Initial studies in a mouse model of HHcy, in which cystathionine-β-synthase (cbs) was deficient, revealed abnormal RPE cell morphology with features similar to that of AMD upon optical coherence tomography (OCT), fluorescein angiography (FA), histological, and electron microscopic examinations. These features include atrophy, vacuolization, hypopigmentation, thickened basal laminar membrane, hyporeflective lucency, choroidal neovascularization (CNV), and disturbed RPE-photoreceptor relationship. Furthermore, intravitreal injection of Hcy per se in normal wild type (WT) mice resulted in diffuse hyper-fluorescence, albumin leakage, and CNV in the area of RPE. In vitro experiments on ARPE-19 showed that Hcy dose-dependently reduced tight junction protein expression, increased FITC dextran leakage, decreased transcellular electrical resistance, and impaired phagocytic activity. Collectively, our results demonstrated unreported effects of excess Hcy levels on RPE structure and function that lead to the development of AMD-like features.

  2. Molecular mechanism of extrinsic factors affecting anti-aging of stem cells.

    Science.gov (United States)

    Wong, Tzyy Yue; Solis, Mairim Alexandra; Chen, Ying-Hui; Huang, Lynn Ling-Huei

    2015-03-26

    Scientific evidence suggests that stem cells possess the anti-aging ability to self-renew and maintain differentiation potentials, and quiescent state. The objective of this review is to discuss the micro-environment where stem cells reside in vivo, the secreted factors to which stem cells are exposed, the hypoxic environment, and intracellular factors including genome stability, mitochondria integrity, epigenetic regulators, calorie restrictions, nutrients, and vitamin D. Secreted tumor growth factor-β and fibroblast growth factor-2 are reported to play a role in stem cell quiescence. Extracellular matrices may interact with caveolin-1, the lipid raft on cell membrane to regulate quiescence. N-cadherin, the adhesive protein on niche cells provides support for stem cells. The hypoxic micro-environment turns on hypoxia-inducible factor-1 to prevent mesenchymal stem cells aging through p16 and p21 down-regulation. Mitochondria express glucosephosphate isomerase to undergo glycolysis and prevent cellular aging. Epigenetic regulators such as p300, protein inhibitors of activated Stats and H19 help maintain stem cell quiescence. In addition, calorie restriction may lead to secretion of paracrines cyclic ADP-ribose by intestinal niche cells, which help maintain intestinal stem cells. In conclusion, it is crucial to understand the anti-aging phenomena of stem cells at the molecular level so that the key to solving the aging mystery may be unlocked.

  3. MicroRNA regulation of adipose derived stem cells in aging rats.

    Directory of Open Access Journals (Sweden)

    Jia Fei

    Full Text Available BACKGROUND: Perturbations in abdominal fat secreted adipokines play a key role in metabolic syndrome. This process is further altered during the aging process, probably due to alterations in the preadipocytes (aka. stromal vascular fraction cells-SVF cells or adipose derived stem cells-ASCs composition and/or function. Since microRNAs regulate genes involved both in development and aging processes, we hypothesized that the impaired adipose function with aging is due to altered microRNA regulation of adipogenic pathways in SVF cells. METHODOLOGY AND PRINCIPAL FINDINGS: Alterations in mRNA and proteins associated with adipogenic differentiation (ERK5 and PPARg but not osteogenic (RUNX2 pathways were observed in SVF cells isolated from visceral adipose tissue with aging (6 to 30 mo in female Fischer 344 x Brown Norway Hybrid (FBN rats. The impaired differentiation capacity with aging correlated with altered levels of miRNAs involved in adipocyte differentiation (miRNA-143 and osteogenic pathways (miRNA-204. Gain and loss of function studies using premir or antagomir-143 validated the age associated adipocyte dysfunction. CONCLUSIONS AND SIGNIFICANCE: Our studies for the first time indicate a role for miRNA mediated regulation of SVF cells with aging. This discovery is important in the light of the findings that dysfunctional adipose derived stem cells contribute to age related chronic diseases.

  4. Combining magnetic sorting of mother cells and fluctuation tests to analyze genome instability during mitotic cell aging in Saccharomyces cerevisiae.

    Science.gov (United States)

    Patterson, Melissa N; Maxwell, Patrick H

    2014-10-16

    Saccharomyces cerevisiae has been an excellent model system for examining mechanisms and consequences of genome instability. Information gained from this yeast model is relevant to many organisms, including humans, since DNA repair and DNA damage response factors are well conserved across diverse species. However, S. cerevisiae has not yet been used to fully address whether the rate of accumulating mutations changes with increasing replicative (mitotic) age due to technical constraints. For instance, measurements of yeast replicative lifespan through micromanipulation involve very small populations of cells, which prohibit detection of rare mutations. Genetic methods to enrich for mother cells in populations by inducing death of daughter cells have been developed, but population sizes are still limited by the frequency with which random mutations that compromise the selection systems occur. The current protocol takes advantage of magnetic sorting of surface-labeled yeast mother cells to obtain large enough populations of aging mother cells to quantify rare mutations through phenotypic selections. Mutation rates, measured through fluctuation tests, and mutation frequencies are first established for young cells and used to predict the frequency of mutations in mother cells of various replicative ages. Mutation frequencies are then determined for sorted mother cells, and the age of the mother cells is determined using flow cytometry by staining with a fluorescent reagent that detects bud scars formed on their cell surfaces during cell division. Comparison of predicted mutation frequencies based on the number of cell divisions to the frequencies experimentally observed for mother cells of a given replicative age can then identify whether there are age-related changes in the rate of accumulating mutations. Variations of this basic protocol provide the means to investigate the influence of alterations in specific gene functions or specific environmental conditions on

  5. Potassium currents in human myogenic cells from donors of different ages.

    Science.gov (United States)

    Nurowska, Ewa; Dworakowska, Beata; Kloch, Monika; Sobol, Maria; Dołowy, Krzysztof; Wernig, Anton; Ruzzier, Fabio

    2006-06-01

    Ageing in humans is accompanied by a reduction in the capacity of satellite cells to proliferate and the forming myoblasts to fuse. The processes of myoblast differentiation and fusion are associated with specific changes in the cells electrical properties. We wanted to elucidate the possible effects of ageing on these parameters and performed whole-cell patch-clamp recordings on human myoblasts obtained from biopsies of skeletal muscles from 2-, 48- and 76-year-old donors. First, we found that resting membrane potential on the 4th day of differentiation in vitro is less negative in the older than in the younger cells. Moreover, the oldest cells showed a smaller density of outward and inward potassium currents. More cells from the old and middle-age donors have a low (less than -40 mV) potential of activation for the outward potassium current. We conclude that in human myoblasts biophysical properties of potassium currents change with donor age.

  6. Sox4 Links Tumor Suppression to Accelerated Aging in Mice by Modulating Stem Cell Activation

    Directory of Open Access Journals (Sweden)

    Miguel Foronda

    2014-07-01

    Full Text Available Sox4 expression is restricted in mammals to embryonic structures and some adult tissues, such as lymphoid organs, pancreas, intestine, and skin. During embryogenesis, Sox4 regulates mesenchymal and neural progenitor survival, as well as lymphocyte and myeloid differentiation, and contributes to pancreas, bone, and heart development. Aberrant Sox4 expression is linked to malignant transformation and metastasis in several types of cancer. To understand the role of Sox4 in the adult organism, we first generated mice with reduced whole-body Sox4 expression. These mice display accelerated aging and reduced cancer incidence. To specifically address a role for Sox4 in adult stem cells, we conditionally deleted Sox4 (Sox4cKO in stratified epithelia. Sox4cKO mice show increased skin stem cell quiescence and resistance to chemical carcinogenesis concomitantly with downregulation of cell cycle, DNA repair, and activated hair follicle stem cell pathways. Altogether, these findings highlight the importance of Sox4 in regulating adult tissue homeostasis and cancer.

  7. Aging influence on grey matter structural associations within the default mode network utilizing Bayesian network modeling

    Directory of Open Access Journals (Sweden)

    Yan eWang

    2014-05-01

    Full Text Available 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 grey 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 (PCC and increases in connections from left HP to mPFC and right inferior parietal cortex (IPC 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.

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

    Science.gov (United States)

    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.

  9. The relation of structural integrity and task-related functional connectivity in the aging brain.

    Science.gov (United States)

    Burianová, Hana; Marstaller, Lars; Choupan, Jeiran; Sepehrband, Farshid; Ziaei, Maryam; Reutens, David

    2015-10-01

    The relations among structural integrity, functional connectivity (FC), and cognitive performance in the aging brain are still understudied. Here, we used multimodal and multivariate approaches to specifically examine age-related changes in task-related FC, gray-matter volumetrics, white-matter integrity, and performance. Our results are two-fold, showing (i) age-related differences in FC of the working memory network and (ii) age-related recruitment of a compensatory network associated with better accuracy on the task. Increased connectivity in the compensatory network correlates positively with preserved white-matter integrity in bilateral frontoparietal tracks and with larger gray-matter volume of right inferior parietal lobule. These findings demonstrate the importance of structural integrity and FC in working memory performance associated with healthy aging.

  10. Caloric restriction confers persistent anti-oxidative, pro-angiogenic, and anti-inflammatory effects and promotes anti-aging miRNA expression profile in cerebromicrovascular endothelial cells of aged rats.

    Science.gov (United States)

    Csiszar, Anna; Gautam, Tripti; Sosnowska, Danuta; Tarantini, Stefano; Banki, Eszter; Tucsek, Zsuzsanna; Toth, Peter; Losonczy, Gyorgy; Koller, Akos; Reglodi, Dora; Giles, Cory B; Wren, Jonathan D; Sonntag, William E; Ungvari, Zoltan

    2014-08-01

    In rodents, moderate caloric restriction (CR) without malnutrition exerts significant cerebrovascular protective effects, improving cortical microvascular density and endothelium-dependent vasodilation, but the underlying cellular mechanisms remain elusive. To elucidate the persisting effects of CR on cerebromicrovascular endothelial cells (CMVECs), primary CMVECs were isolated from young (3 mo old) and aged (24 mo old) ad libitum-fed and aged CR F344xBN rats. We found an age-related increase in cellular and mitochondrial oxidative stress, which is prevented by CR. Expression and transcriptional activity of Nrf2 are both significantly reduced in aged CMVECs, whereas CR prevents age-related Nrf2 dysfunction. Expression of miR-144 was upregulated in aged CMVECs, and overexpression of miR-144 significantly decreased expression of Nrf2 in cells derived from both young animals and aged CR rats. Overexpression of a miR-144 antagomir in aged CMVECs significantly decreases expression of miR-144 and upregulates Nrf2. We found that CR prevents age-related impairment of angiogenic processes, including cell proliferation, adhesion to collagen, and formation of capillary-like structures and inhibits apoptosis in CMVECs. CR also exerts significant anti-inflammatory effects, preventing age-related increases in the transcriptional activity of NF-κB and age-associated pro-inflammatory shift in the endothelial secretome. Characterization of CR-induced changes in miRNA expression suggests that they likely affect several critical functions in endothelial cell homeostasis. The predicted regulatory effects of CR-related differentially expressed miRNAs in aged CMVECs are consistent with the anti-aging endothelial effects of CR observed in vivo. Collectively, we find that CR confers persisting anti-oxidative, pro-angiogenic, and anti-inflammatory cellular effects, preserving a youthful phenotype in rat cerebromicrovascular endothelial cells, suggesting that through these effects CR may

  11. Quota implementation of the maximum sustainable yield for age-structured fisheries.

    Science.gov (United States)

    Kanik, Zafer; Kucuksenel, Serkan

    2016-06-01

    One of the main goals stated in the proposals for the Common Fisheries Policy (CFP) reform was achieving maximum sustainable yield (MSY) for all European fisheries. In this paper, we propose a fishing rights allocation mechanism or management system, which specifies catch limits for individual fishing fleets to implement MSY harvesting conditions in an age-structured bioeconomic model. An age-structured model in a single species fishery with two fleets having perfect or imperfect fishing selectivity is studied. If fishing technology or gear selectivity depends on the relative age composition of the mature fish stock, fixed harvest proportions, derived from catchability and bycatch coefficients, is not valid anymore. As a result, not only the age-structure and fishing technology but also the estimated level of MSY is steering the allocation of quota shares. The results also show that allocation of quota shares based on historical catches or auctioning may not provide viable solutions to achieve MSY.

  12. Uremia causes premature ageing of the T cell compartment in end-stage renal disease patients

    Directory of Open Access Journals (Sweden)

    Meijers Ruud WJ

    2012-09-01

    Full Text Available Abstract Background End-stage renal disease (ESRD patients treated with renal replacement therapy (RRT have premature immunologically aged T cells which may underlie uremia-associated immune dysfunction. The aim of this study was to investigate whether uremia was able to induce premature ageing of the T cell compartment. For this purpose, we examined the degree of premature immunological T cell ageing by examining the T cell differentiation status, thymic output via T cell receptor excision circle (TREC content and proliferative history via relative telomere length in ESRD patients not on RRT. Results Compared to healthy controls, these patients already had a lower TREC content and an increased T cell differentiation accompanied by shorter telomeres. RRT was able to enhance CD8+ T cell differentiation and to reduce CD8+ T cell telomere length in young dialysis patients. An increased differentiation status of memory CD4+ T cells was also noted in young dialysis patients. Conclusion Based on these results we can conclude that uremia already causes premature immunological ageing of the T cell system and RRT further increases immunological ageing of the CD8+ T cell compartment in particular in young ESRD patients.

  13. Effects of age and sex on the structural, chemical and technological characteristics of mule duck meat.

    Science.gov (United States)

    Baeza, E; Salichon, M R; Marche, G; Wacrenier, N; Dominguez, B; Culioli, J

    2000-07-01

    1. The aim of the study was to analyse the effect of age and sex on the chemical, structural and technological characteristics of mule duck meat. 2. Ten males and 10 females were weighed and slaughtered at 8, 10, 11, 12 and 13 weeks of age. Weight, pH value, colour, tenderness and juice loss of breast muscle were determined. 3. The activities of 3 enzymes (citrate synthase, beta-hydroxyacyl CoA dehydrogenase, lactate dehydrogenase) which indicate muscular metabolic activity were assayed. 4. Chemical composition (moisture, lipids, proteins, minerals, lipid and phospholipid classes, fatty acid composition) of breast muscle was analysed. 5. Fibre type, fibre type percentage and cross-sectional areas were determined using histochemistry and an image analysis system. 6. For growth performance and muscular structure, the ideal slaughter age of mule ducks is 10 weeks of age. Chemical and technological analysis indicated that muscular maturity in Pectoralis major was reached at 11 weeks of age, but, at this age, breast lipid content is high. Moreover, after 10 weeks of age, food costs rapidly increased. 7. Lastly, sexual dimorphism for body weight is minor. In this study, at any given age, no significant differences between males and females were shown. Thus, it is possible to rear both sexes together and to slaughter them at the same age.

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

    Science.gov (United States)

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

    2006-01-01

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

  15. Changes in Circulating B Cell Subsets Associated with Aging and Acute SIV Infection in Rhesus Macaques

    Science.gov (United States)

    Gonzalez, Denise F.; Kieu, Hung T.; Castillo, Luis D.; Messaoudi, Ilhem; Shen, Xiaoying; Tomaras, Georgia D.; Shacklett, Barbara L.; Barry, Peter A.; Sparger, Ellen E.

    2017-01-01

    Aging and certain viral infections can negatively impact humoral responses in humans. To further develop the nonhuman primate (NHP) model for investigating B cell dynamics in human aging and infectious disease, a flow cytometric panel was developed to characterize circulating rhesus B cell subsets. Significant differences between human and macaque B cells included the proportions of cells within IgD+ and switched memory populations and a prominent CD21-CD27+ unswitched memory population detected only in macaques. We then utilized the expanded panel to analyze B cell alterations associated with aging and acute simian immunodeficiency virus (SIV) infection in the NHP model. In the aging study, distinct patterns of B cell subset frequencies were observed for macaques aged one to five years compared to those between ages 5 and 30 years. In the SIV infection study, B cell frequencies and absolute number were dramatically reduced following acute infection, but recovered within four weeks of infection. Thereafter, the frequencies of activated memory B cells progressively increased; these were significantly correlated with the magnitude of SIV-specific IgG responses, and coincided with impaired maturation of anti-SIV antibody avidity, as previously reported for HIV-1 infection. These observations further validate the NHP model for investigation of mechanisms responsible for B cells alterations associated with immunosenescence and infectious disease. PMID:28095513

  16. The Problems of Age in Second-Language Acquisition: Influences from Language, Structure, and Task.

    Science.gov (United States)

    Bialystok, Ellen; Miller, Barry

    1999-01-01

    A grammaticality judgment test based on five structures of English grammar was administered in oral and written form. Two groups were formed by separating participants who began learning English at younger and older than 15 years of age. Performance patterns were different for the two groups, the linguistic structure tested affected participants'…

  17. The emerging age of cell-free synthetic biology.

    Science.gov (United States)

    Smith, Mark Thomas; Wilding, Kristen M; Hunt, Jeremy M; Bennett, Anthony M; Bundy, Bradley C

    2014-08-25

    The engineering of and mastery over biological parts has catalyzed the emergence of synthetic biology. This field has grown exponentially in the past decade. As increasingly more applications of synthetic biology are pursued, more challenges are encountered, such as delivering genetic material into cells and optimizing genetic circuits in vivo. An in vitro or cell-free approach to synthetic biology simplifies and avoids many of the pitfalls of in vivo synthetic biology. In this review, we describe some of the innate features that make cell-free systems compelling platforms for synthetic biology and discuss emerging improvements of cell-free technologies. We also select and highlight recent and emerging applications of cell-free synthetic biology.

  18. Fluorescence-Activated Cell Sorting Analysis of Heterotypic Cell-in-Cell Structures.

    Science.gov (United States)

    He, Meifang; Huang, Hongyan; Wang, Manna; Chen, Ang; Ning, Xiangkai; Yu, Kaitao; Li, Qihong; Li, Wen; Ma, Li; Chen, Zhaolie; Wang, Xiaoning; Sun, Qiang

    2015-04-27

    Cell-in-cell structures (CICs), characterized by the presence of one or more viable cells inside another one, were recently found important player in development, immune homeostasis and tumorigenesis etc. Incompatible with ever-increasing interests on this unique phenomenon, reliable methods available for high throughput quantification and systemic investigation are lacking. Here, we report a flow cytometry-based method for rapid analysis and sorting of heterotypic CICs formed between lymphocytes and tumor cells. In this method, cells were labeled with fluorescent dyes for fluorescence-activated cell sorting (FACS) by flow cytometry, conditions for reducing cell doublets were optimized such that high purity (>95%) of CICs could be achieved. By taking advantage of this method, we analyzed CICs formation between different cell pairs, and found that factors from both internalized effector cells and engulfing target cells affect heterotypic CICs formation. Thus, flow cytometry-based FACS analysis would serve as a high throughput method to promote systemic researches on CICs.

  19. Protection of rubbers against aging with the use of structural, diffusion and kinetic effects

    Energy Technology Data Exchange (ETDEWEB)

    Kablov, V. F., E-mail: kablov@volpi.ru [Volzhsky Polytechnical Institute (branch) Volgograd State Technical University, 42a Engelsa Street, 404121, Volzhsky, Volgograd Region (Russian Federation); Zaikov, G. E., E-mail: chembio@sky.chph.ras.ru [N.M. Emanuel Institute of Biochemical Physics Russian Academy of Sciences, Leninskii prospect 64-188, 119296, Moscow (Russian Federation)

    2014-05-15

    Processes of rubber aging in the different kinetic modes and mathematical models of the processes including aging and destruction processes under extreme conditions have been studied. The aging process for rubbers as thermodynamically open nonlinear systems has also been considered in the paper. It has been revealed that the aging process can be controlled by the internal physical-chemical processes organization and by creation of external influences (by organization of thermodynamic forces and flows). According to the Onsager principle, in certain conditions of aging the conjugation of thermodynamic forces and flows is possible. The diffusion and structural aspects of aging in elastomeric rubbers and articles thereof have been considered. The composite antiaging systems of prolonged action based on the use of microparticles with a saturated solution of the antiagers migrating into an elastomeric matrix at the exploitation have been proposed.

  20. Splenic Stromal Cells from Aged Mice Produce Higher Levels of IL-6 Compared to Young Mice

    Science.gov (United States)

    Park, Jihyun; Miyakawa, Takuya; Shiokawa, Aya; Nakajima-Adachi, Haruyo; Hachimura, Satoshi

    2014-01-01

    Inflamm-aging indicates the chronic inflammatory state resulting from increased secretion of proinflammatory cytokines and mediators such as IL-6 in the elderly. Our principle objective was to identify cell types that were affected with aging concerning IL-6 secretion in the murine model. We compared IL-6 production in spleen cells from both young and aged mice and isolated several types of cells from spleen and investigated IL-6 mRNA expression and protein production. IL-6 protein productions in cultured stromal cells from aged mice spleen were significantly high compared to young mice upon LPS stimulation. IL-6 mRNA expression level of freshly isolated stromal cells from aged mice was high compared to young mice. Furthermore, stromal cells of aged mice highly expressed IL-6 mRNA after LPS injection in vivo. These results suggest that stromal cells play a role in producing IL-6 in aged mice and imply that they contribute to the chronic inflammatory condition in the elderly. PMID:24729663

  1. Effect of ageing and pulmonary inflammation on the incidence and number of cross-bridging structures in pneumothorax patients

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Tomoaki; Takahashi, Koji; Aburano, Tamio (Dept. of Radiology, Asahikawa Medical Univ., Asahikawa, Hokkaido (Japan)), email: tomoaki3est@gmail.com

    2011-12-15

    Background. There is an improved prognosis for T4 non-small-cell lung cancer in patients who show particular patterns of direct mediastinal invasion. The particular patterns suggest the presence of direct pathways other than the pulmonary hilum between each of the lungs and the mediastinum/chest wall. Purpose. To determine the incidence and number of such direct pathways in pneumothorax patients as well as the factors that affect the development of these pathways. Material and Methods. Two radiologists independently analyzed multidetector computed tomographic images of 81 patients with pneumothorax to assess the incidence and distribution pattern of the cross-bridging structures in the pleural cavity. Results. Cross-bridging structures were observed in the right pneumothorax in 34/54 (63%) patients and in the left pneumothorax in 19/32 (59%) patients. The number of cross-bridging structures was found to be positively correlated with ageing and pulmonary disease. The distribution patterns of cross-bridging structures were found to be specific in formation and often in repeated locations, regardless of the presence of pulmonary disease or the age of the patient. Conclusion. Cross-bridging structures in pneumothoraces were found more frequently in older patients and in patients with pulmonary disease. However, some of the cross-bridging structures may have been congenital because of their specific formations and repeated locations

  2. Effects of thermal aging on thermo-mechanical behavior of a glass sealant for solid oxide cell applications

    DEFF Research Database (Denmark)

    Abdoli, Hamid; Alizadeh, Parvin; Boccaccini, Dino;

    2014-01-01

    Thermo-mechanical properties of a silicate based glass and its potential use for sealing application in intermediate temperature solid oxide cell (SOC) are presented in this paper. Effects of thermal aging are discussed on structural and microstructural evolution, thermal expansion, viscosity......'s modulus in which a transition between a slow softening (elastic) regime and a rapid softening one was observed. Crystallization induced by thermal aging led to higher creep resistance, but lower capability of crack healing when inspected by electron microscopy. However, potential of stress relaxation...

  3. Contaminant effects on growth, age-structure, and reproduction, of Mytilus edulis from Puget Sound, Washington

    Energy Technology Data Exchange (ETDEWEB)

    Casillas, E.; Kardong, K.; Kagley, A.; Snider, R.G.; Stein, J.E. [NOAA, Seattle, WA (United States). Environmental Conservation Division

    1994-12-31

    Age-length relationships, age structure, and reproductive status (fecundity, egg size) of Mytilus edulis from six sites in central Puget Sound and one site in the relatively pristine area of northern Puget Sound were measured. Mussels from urban-associated sites (areas with elevated sediment concentrations of PAHs, PCBs, and toxic and essential metals) exhibited high tissue burdens of these contaminants. Age length relationships, fitted to the von Bertalanffy equation, showed that the growth of mussels from urban-associated areas was similar, but was lower than in mussels from minimally-contaminated environments. Comparison of mussel population age-structure showed that at urban sites, mussels of comparable size were consistently older than mussels from minimally contaminated areas and the mean age of urban populations was higher than that of rural populations. In mussels from urban sites, gonad mass was lower while number of oocytes/g gonad was similar compared to mussels from minimally-contaminated areas of Puget Sound. Thus, in mussels from urban sites fecundity was reduced compared to mussels of comparable age from reference sites. The findings support the hypothesis that mussels from the urban areas exhibit impaired growth, altered population age-structure, and reproductive impairment as a result of accumulation of chemical contaminants.

  4. Brain Events Underlying Episodic Memory Changes in Aging: A Longitudinal Investigation of Structural and Functional Connectivity.

    Science.gov (United States)

    Fjell, Anders M; Sneve, Markus H; Storsve, Andreas B; Grydeland, Håkon; Yendiki, Anastasia; Walhovd, Kristine B

    2016-03-01

    Episodic memories are established and maintained by close interplay between hippocampus and other cortical regions, but degradation of a fronto-striatal network has been suggested to be a driving force of memory decline in aging. We wanted to directly address how changes in hippocampal-cortical versus striatal-cortical networks over time impact episodic memory with age. We followed 119 healthy participants (20-83 years) for 3.5 years with repeated tests of episodic verbal memory and magnetic resonance imaging for quantification of functional and structural connectivity and regional brain atrophy. While hippocampal-cortical functional connectivity predicted memory change in young, changes in cortico-striatal functional connectivity were related to change in recall in older adults. Within each age group, effects of functional and structural connectivity were anatomically closely aligned. Interestingly, the relationship between functional connectivity and memory was strongest in the age ranges where the rate of reduction of the relevant brain structure was lowest, implying selective impacts of the different brain events on memory. Together, these findings suggest a partly sequential and partly simultaneous model of brain events underlying cognitive changes in aging, where different functional and structural events are more or less important in various time windows, dismissing a simple uni-factorial view on neurocognitive aging.

  5. Precision of hard structures used to estimate age of mountain Whitefish (Prosopium williamsoni)

    Science.gov (United States)

    Watkins, Carson J.; Ross, Tyler J.; Hardy, Ryan S.; Quist, Michael

    2015-01-01

    The mountain whitefish (Prosopium williamsoni) is a widely distributed salmonid in western North America that has decreased in abundance over portions of its distribution due to anthropogenic disturbances. In this investigation, we examined precision of age estimates derived from scales, pectoral fin rays, and sagittal otoliths from 167 mountain whitefish. Otoliths and pectoral fin rays were mounted in epoxy and cross-sectioned before examination. Scales were pressed onto acetate slides and resulting impressions were examined. Between-reader precision (i.e., between 2 readers), between-reader variability, and reader confidence ratings were compared among hard structures. Coefficient of variation (CV) in age estimates was lowest and percentage of exact agreement (PA-0) was highest for scales (CV = 5.9; PA-0 = 70%) compared to pectoral fin rays (CV =11.0; PA-0 = 58%) and otoliths (CV = 12.3; PA-0 = 55%). Median confidence ratings were significantly different (P ≤ 0.05) among all structures, with scales having the highest median confidence. Reader confidence decreased with fish age for scales and pectoral fin rays, but reader confidence increased with fish age for otoliths. In general, age estimates were more precise and reader confidence was higher for scales compared to pectoral fin rays and otoliths. This research will help fisheries biologists in selecting the most appropriate hard structure to use for future age and growth studies on mountain whitefish. In turn, selection of the most precise hard structure will lead to better estimates of dynamic rate functions.

  6. Aging in Sickle Cell Disease: Co-morbidities and New Issues in Management.

    Science.gov (United States)

    Sandhu, Manpreet K; Cohen, Alice

    2015-01-01

    Availability of hydroxyurea (HU) coupled with early therapeutic interventions has increased the life expectancy of patients with sickle cell disease. Hence, the sickle cell community needs to be aware of common diseases of aging that survivors are predisposed to. We chose to investigate the sickle cell disease-related complications as well as non sickle cell disease-related medical problems of aging in 45 sickle cell patients over the age of 40 years. The most frequent chronic complications of sickle cell disease were elevated tricuspid regurgitant jet velocity on echocardiogram, chronic renal disease, iron overload and leg ulcers. Medical co-morbidities in this patient group included hypertension, diabetes mellitus (DM), hypercholesterolemia and symptomatic coronary artery disease (CAD). In our cohort, only 38.0% had a primary care doctor. Only 11.0% over age 50 had a screening colonoscopy, and of the women, 42.0% had a screening mammography. Medical co-morbidities and lack of health maintenance in older sickle cell patients are likely to impact overall health and mortality. Aging patients with sickle cell disease may benefit from a primary medical home for age appropriate comprehensive health care.

  7. A longitudinal study of structural brain network changes with normal aging

    Directory of Open Access Journals (Sweden)

    Kai eWu

    2013-04-01

    Full Text Available The aim of this study was to investigate age-related changes in the topological organization of structural brain networks by applying a longitudinal design over 6 years. Structural brain networks were derived from measurements of regional gray matter volume and were constructed in age-specific groups from baseline and follow-up scans. The structural brain networks showed economical small-world properties, providing high global and local efficiency for parallel information processing at low connection costs. In the analysis of the global network properties, the local and global efficiency of the baseline scan were significantly lower compared to the follow-up scan. Moreover, the annual rate of changes in local and global efficiency showed a positive and negative quadratic correlation with the baseline age, respectively; both curvilinear correlations peaked at approximately the age of 50. In the analysis of the regional nodal properties, significant negative correlations between the annual rate of changes in nodal strength and the baseline age were found in the brain regions primarily involved in the visual and motor/ control systems, whereas significant positive quadratic correlations were found in the brain regions predominately associated with the default-mode, attention, and memory systems. The results of the longitudinal study are consistent with the findings of our previous cross-sectional study: the structural brain networks develop into a fast distribution from young to middle age (approximately 50 years old and eventually became a fast localization in the old age. Our findings elucidate the network topology of structural brain networks and its longitudinal changes, thus enhancing the understanding of the underlying physiology of normal aging in the human brain.

  8. Effects of age, task performance, and structural brain development on face processing.

    Science.gov (United States)

    Cohen Kadosh, Kathrin; Johnson, Mark H; Dick, Frederic; Cohen Kadosh, Roi; Blakemore, Sarah-Jayne

    2013-07-01

    In this combined structural and functional MRI developmental study, we tested 48 participants aged 7-37 years on 3 simple face-processing tasks (identity, expression, and gaze task), which were designed to yield very similar performance levels across the entire age range. The same participants then carried out 3 more difficult out-of-scanner tasks, which provided in-depth measures of changes in performance. For our analysis we adopted a novel, systematic approach that allowed us to differentiate age- from performance-related changes in the BOLD response in the 3 tasks, and compared these effects to concomitant changes in brain structure. The processing of all face aspects activated the core face-network across the age range, as well as additional and partially separable regions. Small task-specific activations in posterior regions were found to increase with age and were distinct from more widespread activations that varied as a function of individual task performance (but not of age). Our results demonstrate that activity during face-processing changes with age, and these effects are still observed when controlling for changes associated with differences in task performance. Moreover, we found that changes in white and gray matter volume were associated with changes in activation with age and performance in the out-of-scanner tasks.

  9. Brain white matter structure and information processing speed in healthy older age.

    Science.gov (United States)

    Kuznetsova, Ksenia A; Maniega, Susana Muñoz; Ritchie, Stuart J; Cox, Simon R; Storkey, Amos J; Starr, John M; Wardlaw, Joanna M; Deary, Ian J; Bastin, Mark E

    2016-07-01

    Cognitive decline, especially the slowing of information processing speed, is associated with normal ageing. This decline may be due to brain cortico-cortical disconnection caused by age-related white matter deterioration. We present results from a large, narrow age range cohort of generally healthy, community-dwelling subjects in their seventies who also had their cognitive ability tested in youth (age 11 years). We investigate associations between older age brain white matter structure, several measures of information processing speed and childhood cognitive ability in 581 subjects. Analysis of diffusion tensor MRI data using Tract-based Spatial Statistics (TBSS) showed that all measures of information processing speed, as well as a general speed factor composed from these tests (g speed), were significantly associated with fractional anisotropy (FA) across the white matter skeleton rather than in specific tracts. Cognitive ability measured at age 11 years was not associated with older age white matter FA, except for the g speed-independent components of several individual processing speed tests. These results indicate that quicker and more efficient information processing requires global connectivity in older age, and that associations between white matter FA and information processing speed (both individual test scores and g speed), unlike some other aspects of later life brain structure, are generally not accounted for by cognitive ability measured in youth.

  10. TGFβ lengthens the G1 phase of stem cells in aged mouse brain.

    Science.gov (United States)

    Daynac, Mathieu; Pineda, Jose R; Chicheportiche, Alexandra; Gauthier, Laurent R; Morizur, Lise; Boussin, François D; Mouthon, Marc-André

    2014-12-01

    Neurogenesis decreases during aging causing a progressive cognitive decline but it is still controversial whether proliferation defects in neurogenic niches result from a loss of neural stem cells or from an impairment of their progression through the cell cycle. Using an accurate fluorescence-activated cell sorting technique, we show that the pool of neural stem cells is maintained in the subventricular zone of middle-aged mice while they have a reduced proliferative potential eventually leading to the subsequent decrease of their progeny. In addition, we demonstrate that the G1 phase is lengthened during aging specifically in activated stem cells, but not in transit-amplifying cells, and directly impacts on neurogenesis. Finally, we report that inhibition of TGFβ signaling restores cell cycle progression defects in stem cells. Our data highlight the significance of cell cycle dysregulation in stem cells in the aged brain and provide an attractive foundation for the development of anti-TGFβ regenerative therapies based on stimulating endogenous neural stem cells.

  11. Derivation of Pluripotent Cells from Mouse SSCs Seems to Be Age Dependent

    Directory of Open Access Journals (Sweden)

    Hossein Azizi

    2016-01-01

    Full Text Available Here, we aimed to answer important and fundamental questions in germ cell biology with special focus on the age of the male donor cells and the possibility to generate embryonic stem cell- (ESC- like cells. While it is believed that spermatogonial stem cells (SSCs and truly pluripotent ESC-like cells can be isolated from adult mice, it remained unknown if the spontaneous conversion of SSCs to ESC-like cells fails at some age. Similarly, there have been differences in the literature about the duration of cultures during which ESC-like cells may appear. We demonstrate the possibility to derive ESC-like cells from SSC cultures until they reach adolescence or up to 7 weeks of age, but we point out the impossibility to derive these cells from older, mature adult mice. The inability of real adult SSCs to shift to a pluripotent state coincides with a decline in expression of the core pluripotency genes Oct4, Nanog, and Sox2 in SSCs with age. At the same time genes of the spermatogonial differentiation pathway increase. The generated ESC-like cells were similar to ESCs and express pluripotency markers. In vitro they differentiate into all three germ lineages; they form complex teratomas after transplantation in SCID mice and produce chimeric mice.

  12. How T follicular helper cells and the germinal centre response change with age.

    Science.gov (United States)

    Linterman, Michelle A

    2014-01-01

    Normal ageing is accompanied by a decline in the function of the immune system that causes an increased susceptibility to infections and an impaired response to vaccination in older individuals. This results in an increased disease burden in the aged population, even with good immunisation programmes in place. The decreased response to vaccination is partly due to the diminution of the germinal centre response with age, caused by impaired T-cell help to B cells. Within the germinal centre, T-cell help is provided by a specialised subset of CD4(+) T cells; T follicular helper (Tfh) cells. Tfh cells provide survival and selection signals to germinal centre B cells, allowing them to egress from the germinal centre and become long-live plasma cells or memory B cells, and provide life-long protection against subsequent infection. This review will discuss the cellular and molecular changes in both Tfh cells and germinal centre B cells that occur with advancing age, which result in a smaller germinal centre response and a less effective response to immunisation.

  13. Uneven distribution of NG2 cells in the rat cerebellar vermis and changes in aging

    Directory of Open Access Journals (Sweden)

    S. Lomoio

    2012-06-01

    Full Text Available We describe by NG2 (neuron-glia chondroitin sulphate proteoglycan 2 immunocytochemistry an uneven distribution of NG2 glial cells in the rat cerebellum, being them more represented in the central lobules of the cerebellar vermis, belonging to the cerebrocerebellum. The cerebellar distribution of NG2 cells changes in aging rats, in which the area where the cells appear to be densely scattered throughout all cerebellar layers involves also more rostral and caudal lobules. In addition, in aging rats, in the most rostral and caudal lobules belonging to the spinocerebellum, punctate reaction product is present at the apical pole of Purkinje cells, i.e. in the area where the majority of synapses between olivary climbing fibers and Purkinje cells occur. Data suggest that the different distribution of NG2 cells is correlated to differences in physiology among cerebellar areas and reflects changes during aging.

  14. Human Epithelial Cells Increase Their Rigidity with Ageing In-vitro: Direct Measurements

    Science.gov (United States)

    Berdyyeva, Tamara; Woodworth, Craig; Sokolov, Igor

    2004-03-01

    The decrease in elasticity of epithelial tissues with ageing contributes to many human diseases. This change was previously explained by the increase in crosslinking of extracellular matrix proteins that normally provide elasticity. Here we show that individual human epithelial cells also become significantly more rigid during ageing in vitro. Using atomic force microscopy (AFM), we found that each cell has at least three areas of different rigidity: the area over the nucleus, the cytoplasm, and the cell edge. The Young's modulus for each area is consistently 2-4 times higher in old senescent cells than in young cells. Direct visualization of the cytoskeleton of ageing cells using a novel method involving the AFM, demonstrated that increased rigidity is associated with a higher density of the cytoskeleton fibres in both cytoplasmic and edge areas.

  15. Uneven distribution of NG2 cells in the rat cerebellar vermis and changes in aging

    Science.gov (United States)

    Lomoio, S.; Necchi, D.; Scherini, E.

    2012-01-01

    We describe by NG2 (neuron-glia chondroitin sulphate proteoglycan 2) immunocytochemistry an uneven distribution of NG2 glial cells in the rat cerebellum, being them more represented in the central lobules of the cerebellar vermis, belonging to the cerebrocerebellum. The cerebellar distribution of NG2 cells changes in aging rats, in which the area where the cells appear to be densely scattered throughout all cerebellar layers involves also more rostral and caudal lobules. In addition, in aging rats, in the most rostral and caudal lobules belonging to the spinocerebellum, punctate reaction product is present at the apical pole of Purkinje cells, i.e. in the area where the majority of synapses between olivary climbing fibers and Purkinje cells occur. Data suggest that the different distribution of NG2 cells is correlated to differences in physiology among cerebellar areas and reflects changes during aging. PMID:23027343

  16. Structure of physical, psycho-physiological development and physical preparedness of children of preschool age.

    Directory of Open Access Journals (Sweden)

    Kozina Zh.L.

    2011-08-01

    Full Text Available The results of determination of structure of physical development are resulted, psycho-physiological possibilities and physical preparedness of children of age-dependent groups, 1-2, 3-4 and 4-5 years. It is set that development of children from 1 to 5 years takes place getertimely. There is a considerable role of indexes in the initial probed age-dependent period (1-2 years there is a considerable role of indexes of physical development in development of physical qualities and psycho-physiological possibilities. In age 3-4 the role of level of development of physical qualities and psycho-physiological possibilities increases in the structure of complex preparedness, and in an age-dependent period 4-5 years again there is an increase of role of physical development with the maintain of role of physical preparedness and psycho-physiological possibilities.

  17. Changes of population by age and gender structure of Regions in the Republic of Macedonia

    Directory of Open Access Journals (Sweden)

    Resul Hamiti

    2015-07-01

    Full Text Available This paper analyzes the changes of population by age and the gender structure in the regions of the Republic of Macedonia. Age and gender is very important not only for the development of demographic process but also for the development of regions. They play an important role in planning the health care needs and other services with the socio-economic and cultural character. In this sense they affect the performance of demographic processes (births, deaths, marriages, etc. and are a result of bilateral relations fertility, mortality, migration movements and other social processes. The main objective of this paper is to identify the aging phenomenon of population in state level and regions. This paper also dedicates special importance to the changes of age and sex structure, during the period between1981-2014 in the regions of the republic of Macedonia.

  18. Increased mammogram-induced DNA damage in mammary epithelial cells aged in vitro.

    Science.gov (United States)

    Hernández, Laia; Terradas, Mariona; Martín, Marta; Feijoo, Purificación; Soler, David; Tusell, Laura; Genescà, Anna

    2013-01-01

    Concerned about the risks of mammography screening in the adult population, we analyzed the ability of human mammary epithelial cells to cope with mammogram-induced DNA damage. Our study shows that an X-ray dose of 20 mGy, which is the standard dose received by the breast surface per two-view mammogram X-ray exploration, induces increased frequencies of DNA double-strand breaks to in vitro aged-but not to young-human mammary epithelial cells. We provide evidence that aged epithelial breast cells are more radiosensitive than younger ones. Our studies point to an inefficient damage response of aged cells to low-dose radiation, this being due to both delayed and incomplete mobilization of repair proteins to DNA strand breaks. This inefficient damage response is translated into an important delay in double-strand break disappearance and consequent accumulation of unrepaired DNA breaks. The result of this is a significant increase in micronuclei frequency in the in vitro aged mammary epithelial cells exposed to doses equivalent to a single mammogram X-ray exploration. Since our experiments were carried out in primary epithelial cell cultures in which cells age at the same time as they undergo replication-dependent telomere shortening, we needed to determine the contribution of these two factors to their phenotype. In this paper, we report that the exogenous expression of human telomerase retrotranscriptase in late population doubling epithelial cells does not rescue its delayed repair phenotype. Therefore, retarded DNA break repair is a direct consequence of cellular aging itself, rather than a consequence of the presence of dysfunctional telomeres. Our findings of long-lasting double strand breaks and incomplete DNA break repair in the in vitro aged epithelial cells are in line with the increased carcinogenic risks of radiation exposures at older ages revealed by epidemiologic studies.

  19. Increased mammogram-induced DNA damage in mammary epithelial cells aged in vitro.

    Directory of Open Access Journals (Sweden)

    Laia Hernández

    Full Text Available Concerned about the risks of mammography screening in the adult population, we analyzed the ability of human mammary epithelial cells to cope with mammogram-induced DNA damage. Our study shows that an X-ray dose of 20 mGy, which is the standard dose received by the breast surface per two-view mammogram X-ray exploration, induces increased frequencies of DNA double-strand breaks to in vitro aged-but not to young-human mammary epithelial cells. We provide evidence that aged epithelial breast cells are more radiosensitive than younger ones. Our studies point to an inefficient damage response of aged cells to low-dose radiation, this being due to both delayed and incomplete mobilization of repair proteins to DNA strand breaks. This inefficient damage response is translated into an important delay in double-strand break disappearance and consequent accumulation of unrepaired DNA breaks. The result of this is a significant increase in micronuclei frequency in the in vitro aged mammary epithelial cells exposed to doses equivalent to a single mammogram X-ray exploration. Since our experiments were carried out in primary epithelial cell cultures in which cells age at the same time as they undergo replication-dependent telomere shortening, we needed to determine the contribution of these two factors to their phenotype. In this paper, we report that the exogenous expression of human telomerase retrotranscriptase in late population doubling epithelial cells does not rescue its delayed repair phenotype. Therefore, retarded DNA break repair is a direct consequence of cellular aging itself, rather than a consequence of the presence of dysfunctional telomeres. Our findings of long-lasting double strand breaks and incomplete DNA break repair in the in vitro aged epithelial cells are in line with the increased carcinogenic risks of radiation exposures at older ages revealed by epidemiologic studies.

  20. Spring hunting of European roe deer in Vojvodina: Age structure and trophy value

    OpenAIRE

    2005-01-01

    Trophies of the European roe deer are the main source of income in Vojvodina hunting grounds managed by hunting associations. The specificity of site conditions (agro-biotope) aggravates the hunting, especially regarding the assessment of the age and trophy value, so the best males are hunted before they reach the culmination of trophy development. The aim of this study is to define reliably the age of males in spring hunting and to analyze their trophy structure. The study results show that,...

  1. Detecting age-structured effects in growth performance of coral reef fish juveniles

    OpenAIRE

    Mellin, Camille; Galzin, R.; Ponton, Dominique; Vigliola, Laurent

    2009-01-01

    The growth performance of coral reef fish juveniles collected in different habitats is often used as a proxy for habitat quality for juveniles. However, back-calculated growth trajectories of juveniles may be age-structured, for instance, because of potential differences in initial offspring size and/or quality or size-selective mortality. A novel approach is proposed to isolate growth performance of coral reef fish juveniles from potential age-based factors. Juveniles of Chromis viridis (Pom...

  2. Changes of number of cells expressing proliferation and progenitor cell markers with age in rabbit intervertebral discs

    Institute of Scientific and Technical Information of China (English)

    Miersalijiang Yasen; Qinming Fei; William C Hutton; Jian Zhang; Jian Dong; Xiaoxing Jiang; Feng Zhang

    2013-01-01

    Basic knowledge about the normal regeneration process within the intervertebral disc (IVD) is important to the understanding of the underlying biology.The presence of progenitor and stem cells in IVD has been verified.However,changes of number of progenitor and stem cells with age are still unknown.In this study,changes of cell proliferation and progenitor cell markers with age in IVD cells from rabbits of two different ages were investigated using flow cytometry,immunohistochemistry,real-time polymerase chain reaction,and western blot analysis.Proliferating cell nuclear antigen (PCNA) was chosen as a marker for proliferation,and Notch1,Jagged1,C-KIT,CD166 were chosen as stem/progenitor cell markers.Cell cycle analysis showed that cell number in the G2/M phase of the young rabbits was significantly higher than that of mature rabbits.Immunohistochemical staining demonstrated the expression of PCNA,C-KIT,CD166,Notch1,and Jagged1 in both young and mature annulus fibrosus (AF).Protein expressions of these cell markers in the young rabbits were all significantly higher than those in the mature rabbits.The expression levels of PCNA,CD166,C-KIT,Jagged1 were significantly higher in the AF,and PCNA,C-KIT in the nucleus pulposus from young rabbits than those from the mature rabbits.These findings demonstrated that both proliferation and progenitor cells exist in rabbit IVDs and the number of cells expressing proliferation and progenitor cell markers decreases with age in the rabbit IVD cells.Methods that are designed to maintain the endogenous progenitor cells and stimulate their proliferation could be successful in preventing or inhibiting degenerative disc disease.

  3. Biological character of human adipose-derived adult stem cells and influence of donor age on cell replication in culture

    Institute of Scientific and Technical Information of China (English)

    LEI Lei; LIAO WeiMing; SHENG PuYi; FU Ming; HE AiShan; HUANG Gang

    2007-01-01

    To investigate the biological character of human adipose-derived adult stem cells (hADAS cells) when cultured in vitro and the relationship between hADAS cell's replication activity and the donor's age factor, and to assess the stem cells as a new source for tissue engineering, hADAS cells are isolated from human adipose tissue of different age groups (from adolescents to olds: <20 years old, 21-40years old, 41-60 years old and >61 years old groups). The protein markers (CD29, CD34, CD44, CD45,CD49d, HLA-DR, CD106) of hADAS cells were detected by flow cytometry (FCM) to identify the stem cell,and the cell cycle was examined for P20 hADAS cells to evaluate the safety of the subculture in vitro.The generative activity of hADAS cells in different age groups was also examined by MTT method. The formula "TD = t log2/logNt - logN0 "was used to get the time doubling (TD) of the cells. The results showed that the cells kept heredity stabilization by chromosome analysis for at least 20 passages. The TD of these cells increased progressively by ageing, and the TD of the <20 years old group was lower than that of the >61 years old group (statistical analysis of variance (ANOVA), P=-0.002, P<0.05). These findings suggested that a higher level of hADAS cells replication activity was found in the younger donators, and they represent novel and valuable seed cells for studies of tissue engineering.

  4. Arterial structure and function in vascular ageing: are you as old as your arteries?

    Science.gov (United States)

    Thijssen, Dick H J; Carter, Sophie E; Green, Daniel J

    2016-04-15

    Advancing age may be the most potent independent predictor of future cardiovascular events, a relationship that is not fully explained by time-related changes in traditional cardiovascular risk factors. Since some arteries exhibit differential susceptibility to atherosclerosis, generalisations regarding the impact of ageing in humans may be overly simplistic, whereas in vivo assessment of arterial function and health provide direct insight. Coronary and peripheral (conduit, resistance and skin) arteries demonstrate a gradual, age-related impairment in vascular function that is likely to be related to a reduction in endothelium-derived nitric oxide bioavailability and/or increased production of vasoconstrictors (e.g. endothelin-1). Increased exposure and impaired ability for defence mechanisms to resist oxidative stress and inflammation, but also cellular senescence processes, may contribute to age-related changes in vascular function and health. Arteries also undergo structural changes as they age. Gradual thickening of the arterial wall, changes in wall content (i.e. less elastin, advanced glycation end-products) and increase in conduit artery diameter are observed with older age and occur similarly in central and peripheral arteries. These changes in structure have important interactive effects on artery function, with increases in small and large arterial stiffness representing a characteristic change with older age. Importantly, direct measures of arterial function and structure predict future cardiovascular events, independent of age or other cardiovascular risk factors. Taken together, and given the differential susceptibility of arteries to atherosclerosis in humans, direct measurement of arterial function and health may help to distinguish between biological and chronological age-related change in arterial health in humans.

  5. Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells

    DEFF Research Database (Denmark)

    Dokkedahl, Karin Stenderup; Justesen, Jeannette; Clausen, Christian

    2003-01-01

    donors were able to form similar amounts of mineralized matrix in vitro and of normal lamellar bone in vivo. In adipogenic medium similar numbers of adipocytes formed in cultures of young and old donors. In conclusion, aging is associated with decreased proliferative capacity of osteoprogenitor cells......Age-related decrease in bone formation is well described. However, the cellular causes are not known. Thus, we have established cultures of bone marrow stromal cells (MSC) from young (aged 18-29 years, n = 6) and old (aged 68-81 years, n = 5) donors. MSC were serially passaged until reaching......, suggesting that decreased osteoblastic cell number, and not function, leads to age-related decrease in bone formation....

  6. Crystal Structure Studies of Human Dental Apatite as a Function of Age

    Directory of Open Access Journals (Sweden)

    Th. Leventouri

    2009-01-01

    Full Text Available Studies of the average crystal structure properties of human dental apatite as a function of age in the range of 5–87 years are reported. The crystallinity of the dental hydroxyapatite decreases with the age. The a-lattice constant that is associated with the carbonate content in carbonate apatite decreases with age in a systematic way, whereas the c-lattice constant does not change significantly. Thermogravimetric measurements demonstrate an increase of the carbonate content with the age. FTIR spectroscopy reveals both B and A-type carbonate substitutions with the B-type greater than the A-type substitution by a factor up to ~5. An increase of the carbonate content as a function of age can be deduced from the ratio of the 2CO3 to the 1PO4 IR modes.

  7. Slow and fast scales for superprocess limits of age-structured populations

    CERN Document Server

    Méléard, Sylvie

    2010-01-01

    A superprocess limit for an interacting birth-death particle system modelling a population with trait and age-structures is established. Traits of newborn offspring are inherited from the parents except when mutations occur, while ages are set to zero. Because of interactions between individuals, standard approaches based on the Laplace transform do not hold. We use a martingale problem approach and a separation of the slow (trait) and fast (age) scales. While the trait marginals converge in a pathwise sense to a superprocess, the age dynamics, on another time scale, averages to an equilibrium that depends on traits. The convergence of the whole process depending on trait and age, only holds for finite-dimensional time-marginals. We apply our results to the study of examples illustrating different cases of trade-off between competition and senescence.

  8. Age Differences in Interhemispheric Interactions: Callosal Structure, Physiological Function, and Behavior

    Directory of Open Access Journals (Sweden)

    Brett W Fling

    2011-03-01

    Full Text Available There is a fundamental gap in understanding how brain structural and functional network connectivity are interrelated, how they change with age, and how such changes contribute to older adults’ sensorimotor deficits. Recent neuroimaging approaches including resting state functional connectivity MRI (fcMRI and diffusion tensor imaging (DTI have been used to assess brain functional (fcMRI and structural (DTI network connectivity, allowing for more integrative assessments of distributed neural systems than in the past. Declines in corpus callosum size and microstructure with advancing age have been well documented, but their contributions to age deficits in unimanual and bimanual function are not well defined. Our recent work implicates age-related declines in callosal size and integrity as a key contributor to unimanual and bimanual control deficits. Moreover, our data provide evidence for a fundamental shift in the balance of excitatory and inhibitory interhemispheric processes that occurs with age, resulting in age differences in the relationship between functional and structural network connectivity. Training studies suggest that the balance of interhemispheric interactions can be shifted with experience, making this a viable target for future interventions.

  9. Effects of Aging Time and Sintering Temperatures on Thermal, Structural and Morphological Properties of Coralline Hydroxyapatite

    Directory of Open Access Journals (Sweden)

    MANINDER SINGH MEHTA

    2016-02-01

    Full Text Available Biphasic Calcium Phosphate bioceramics belong to a group of bone substitute biomaterials comprised of an intimate mixture of Hydroxyapatite (HAP and β-Tricalcium Phosphates. In the present work, Coralline Hydroxyapatite was synthesized using wet precipitation method. Powder particles were aged for 24 and 48 hours at 5. X-Ray Diffraction, Fourier Transform Infrared and Thermogravimetric spectroscopic techniques were used. Biphasic Calcium Phosphate was identified as the chief structural constitution of the synthetic powders. Weight fraction of Hydroxyapatite increased with the rise of sintering temperature. Aging time of 24 hours yielded maximum amount of hydroxyapatite, thus confirming optimum aging time for the synthesis of Coralline Hydroxyapatite.

  10. Disentangling normal aging from Alzheimer's disease in structural magnetic resonance images.

    Science.gov (United States)

    Lorenzi, Marco; Pennec, Xavier; Frisoni, Giovanni B; Ayache, Nicholas

    2015-01-01

    The morphology observed in the brains of patients affected by Alzheimer's disease (AD) is a combination of different biological processes, such as normal aging and the pathological matter loss specific to AD. The ability to differentiate between these biological factors is fundamental to reliably evaluate pathological AD-related structural changes, especially in the earliest phase of the disease, at prodromal and preclinical stages. Here we propose a method based on non-linear image registration to estimate and analyze from observed brain morphologies the relative contributions from aging and pathology. In particular, we first define a longitudinal model of the brain's normal aging process from serial T1-weight magnetic resonance imaging scans of 65 healthy participants. The longitudinal model is then used as a reference for the cross-sectional analysis. Given a new brain image, we then estimate its anatomical age relative to the aging model; this is defined as a morphological age shift with respect to the average age of the healthy population at baseline. Finally, we define the specific morphological process as the remainder of the observed anatomy after the removal of the estimated normal aging process. Experimental results from 105 healthy participants, 110 subjects with mild cognitive impairment (MCI), 86 with MCI converted to AD, and 134 AD patients provide a novel description of the anatomical changes observed across the AD time span: normal aging, normal aging at risk, conversion to MCI, and the latest stages of AD. More advanced AD stages are associated with an increased morphological age shift in the brain and with strong disease-specific morphological changes affecting mainly ventricles, temporal poles, the entorhinal cortex, and hippocampi. Our model shows that AD is characterized by localized disease-specific brain changes as well as by an accelerated global aging process. This method may thus represent a more precise instrument to identify potential

  11. Human epithelial cells increase their rigidity with ageing in vitro: direct measurements

    Science.gov (United States)

    Berdyyeva, Tamara K.; Woodworth, Craig D.; Sokolov, Igor

    2005-01-01

    The decrease in elasticity of epithelial tissues with ageing contributes to many human diseases. This change was previously attributed to increased crosslinking of extracellular matrix proteins. Here we show that individual human epithelial cells also become significantly more rigid during ageing in vitro. Using atomic force microscopy (AFM), we found that the Young's modulus of viable cells was consistently increased two- to four-fold in older versus younger cells. Direct visualization of the cytoskeleton using a novel method involving the AFM suggested that increased rigidity of ageing cells was due to a higher density of cytoskeletal fibres. Our results identify a unique mechanism that might contribute to the age-related loss of elasticity in epithelial tissues.

  12. Human epithelial cells increase their rigidity with ageing in vitro: direct measurements

    Energy Technology Data Exchange (ETDEWEB)

    Berdyyeva, Tamara K [Department of Physics, Clarkson University, Potsdam, NY 13699-5820 (United States); Woodworth, Craig D [Department of Biology, Clarkson University, NY 13699 (United States); Sokolov, Igor [Department of Physics, Clarkson University, Potsdam, NY 13699-5820 (United States)

    2005-01-07

    The decrease in elasticity of epithelial tissues with ageing contributes to many human diseases. This change was previously attributed to increased crosslinking of extracellular matrix proteins. Here we show that individual human epithelial cells also become significantly more rigid during ageing in vitro. Using atomic force microscopy (AFM), we found that the Young's modulus of viable cells was consistently increased two- to four-fold in older versus younger cells. Direct visualization of the cytoskeleton using a novel method involving the AFM suggested that increased rigidity of ageing cells was due to a higher density of cytoskeletal fibres. Our results identify a unique mechanism that might contribute to the age-related loss of elasticity in epithelial tissues.

  13. Do brain image databanks support understanding of normal ageing brain structure? A systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Dickie, David Alexander; Job, Dominic E.; Wardlaw, Joanna M. [University of Edinburgh, Division of Clinical Neurosciences, Western General Hospital, Brain Research Imaging Centre (BRIC), Edinburgh (United Kingdom); Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE), Edinburgh (United Kingdom); Poole, Ian [Toshiba Medical Visualisation Systems Europe, Ltd., Edinburgh (United Kingdom); Ahearn, Trevor S.; Staff, Roger T.; Murray, Alison D. [University of Aberdeen, Aberdeen Biomedical Imaging Centre, Aberdeen (United Kingdom); Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE), Edinburgh (United Kingdom)

    2012-07-15

    To document accessible magnetic resonance (MR) brain images, metadata and statistical results from normal older subjects that may be used to improve diagnoses of dementia. We systematically reviewed published brain image databanks (print literature and Internet) concerned with normal ageing brain structure. From nine eligible databanks, there appeared to be 944 normal subjects aged {>=}60 years. However, many subjects were in more than one databank and not all were fully representative of normal ageing clinical characteristics. Therefore, there were approximately 343 subjects aged {>=}60 years with metadata representative of normal ageing, but only 98 subjects were openly accessible. No databank had the range of MR image sequences, e.g. T2*, fluid-attenuated inversion recovery (FLAIR), required to effectively characterise the features of brain ageing. No databank supported random subject retrieval; therefore, manual selection bias and errors may occur in studies that use these subjects as controls. Finally, no databank stored results from statistical analyses of its brain image and metadata that may be validated with analyses of further data. Brain image databanks require open access, more subjects, metadata, MR image sequences, searchability and statistical results to improve understanding of normal ageing brain structure and diagnoses of dementia. (orig.)

  14. Components of Appearance in the Structure of Perception of Visual Representations of Age

    Directory of Open Access Journals (Sweden)

    Shkurko T.A.

    2015-12-01

    Full Text Available The article discusses the problem of perception of age (one’s own and that of other people, which is regarded as a special case of social perception. The aim of this study was to analyze the components of another person’s appearance in the structure of perception of visual representations of age. For these purposes the authors created a special technique, “Identifying Age through Photo Visualization” (Shkurko T.A., Nikolaeva E. G.. The study enrolled 20 individuals (10 men, 10 women aged 18 to 58 years as “models” (i.e. objects of perception and 60 individuals (47 women and 13 men aged 18 to 77 years as subjects of perception. The paper shows that in the structure of perception of visual representations of age the most important are stable, moderately stable and dynamic components of appearance, among which the stable parameters prevail. The face as the focus of the stable, moderately stable and dynamic components of appearance is the key element of appearance in one’s perception of other people’s age.

  15. Developing a Computerized Aging Management System for Concrete Structures in Finnish Nuclear Power Plants

    Directory of Open Access Journals (Sweden)

    Hradil P.

    2013-07-01

    Full Text Available Finland has four nuclear reactors units in two power plants. The first unit started operation in 1977 and in the early 1980's all four units were in use. During the last few years the aging management of the Nuclear Power Plant's (NPP concrete structures has grown an important issue because the existing structures are reaching the end of their licensed operating lifetime (about 40 years. Therefore the nuclear power companies are developing aging management systems to avoid premature degradation of NPP facilities and to be able to extend their operating lifetime. This paper is about the development of a computerized ageing management system for the nuclear power plants concrete structures. The computerized ageing management system is built upon central database and implementation applications. It will assist the personnel of power companies to implement the aging management activities at different phases of the lifetime of a power plant. It will provide systematic methods for planning, surveillance, inspection, monitoring, condition assessment, maintenance and repair of structures.

  16. Developing a Computerized Aging Management System for Concrete Structures in Finnish Nuclear Power Plants

    Science.gov (United States)

    Al-Neshawy, F.; Piironen, J.; Sistonen, E.; Vesikari, E.; Tuomisto, M.; Hradil, P.; Ferreira, M.

    2013-07-01

    Finland has four nuclear reactors units in two power plants. The first unit started operation in 1977 and in the early 1980's all four units were in use. During the last few years the aging management of the Nuclear Power Plant's (NPP) concrete structures has grown an important issue because the existing structures are reaching the end of their licensed operating lifetime (about 40 years). Therefore the nuclear power companies are developing aging management systems to avoid premature degradation of NPP facilities and to be able to extend their operating lifetime. This paper is about the development of a computerized ageing management system for the nuclear power plants concrete structures. The computerized ageing management system is built upon central database and implementation applications. It will assist the personnel of power companies to implement the aging management activities at different phases of the lifetime of a power plant. It will provide systematic methods for planning, surveillance, inspection, monitoring, condition assessment, maintenance and repair of structures.

  17. The effects of migration and fertility on the age-sex structure of Lagos State, Nigeria

    Directory of Open Access Journals (Sweden)

    Esther Ugomma EJEKWUMADU

    2009-12-01

    Full Text Available This research was carried out to appraise the influence of fertility and migration on the age-sex population structure of Lagos State, Nigeria. Respondents were randomly selected and given questionnaire to fill with regards to fertility and migration trends in the study area. Using partial correlation and multiple regression analyses, we determined the influence of migration and fertility on the age structure of the population. The combined effects of the partial correlation of fertility and migration were 0.66 (males and 0.79 (females. The regression analyses yielded influence of fertility of 9.6 and 11.7 for males and females respectively, which far outstrips the influence of migration of 6.4 and 1.5 for males and females respectively on the age-sex structure. Also, the base constant was –5.1 for females and –3.2 for males i.e. the minimum change in age of male and female populations that would occur before the influence of fertility and migration become noticeable. Finally, the socio-economic implications of the age-sex structure were highlighted.

  18. Cancer stem cells in Helicobacter pylori infection and aging: Implications for gastric carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Edi; Levi; Paula; Sochacki; Nabiha; Khoury; Bhaumik; B; Patel; Adhip; PN; Majumdar

    2014-01-01

    AIM: To demonstrated the combined effects of aging and carcinogen treatment on cancer stem/stem-like cells(CSCs) of gastric mucosa in an animal model. METHODS: In this study we investigated the effects of aging and Helicobacter pylori(H. pylori) inflammation as a model for inflammation induced carcinogenesis in human and rat gastric mucosa samples. In aging studies, we compared 4-mo old(young) with 22 mo(aged) old Fischer-344 rats. For human studies, gastric biop-sies and resection specimens representing normal mucosa or different stages of H. pylori gastritis and gastric adenocarcinomas were used for determining the expression of stem cell markers CD166, ALDH1 and LGR5. In addition we performed immunofluorescent double labeling for B-catenin and Lgr5 in both rat and human gastric tissues to examine the status of Wnt signaling in these cells. RESULTS: CSC markers ALDH1, LGR5, and CD166 were expressed in very low levels in normal human gastric mucosa or young rat gastric mucosa. In contrast, level of expression for all three markers significantly increased in H. pylori gastritis and gastric adenocarcinomas as well as in normal gastric mucosa in aged rats. We also observed cytoplasmic B-catenin staining in both aged rat and human H. pylori inflamed gastric mucosa, which were found to be colocalized with Lgr5 immunoreactive cells. The increased number of ALDH1, CD166 and LGR5 positive cells in H. pylori gastritis indicates that increased number of stem-like cells in gastric mucosa is an early event, and may constitute an important step in the progression to neoplasia. CONCLUSION: Our observation of the age-related increase in cancer stem/stem-like cells in the gastric mucosa may explain the increased incidence of gastric cancer during aging. Combination of aging and H. pylori infection may have additive effects in progression to neoplasia.

  19. Biological character of human adipose-derived adult stem cells and influence of donor age on cell replication in culture

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    To investigate the biological character of human adipose-derived adult stem cells (hADAS cells) when cultured in vitro and the relationship between hADAS cell’s replication activity and the donor’s age factor, and to assess the stem cells as a new source for tissue engineering. hADAS cells are isolated from human adipose tissue of different age groups (from adolescents to olds: <20 years old, 21―40 years old, 41―60 years old and >61 years old groups). The protein markers (CD29, CD34, CD44, CD45, CD49d, HLA-DR, CD106) of hADAS cells were detected by flow cytometry (FCM) to identify the stem cell, and the cell cycle was examined for P20 hADAS cells to evaluate the safety of the subculture in vitro. The generative activity of hADAS cells in different age groups was also examined by MTT method. The formula “ log2T D = t logN t ? logN 0” was used to get the time doubling (TD) of the cells. The results showed that the cells kept heredity stabilization by chromosome analysis for at least 20 passages. The TD of these cells increased progressively by ageing, and the TD of the <20 years old group was lower than that of the >61 years old group (statistical analysis of variance (ANOVA), P=0.002, P<0.05). These find- ings suggested that a higher level of hADAS cells replication activity was found in the younger dona- tors, and they represent novel and valuable seed cells for studies of tissue engineering.

  20. Neural stem cells could serve as a therapeutic material for age-related neurodegenerative diseases.

    Science.gov (United States)

    Suksuphew, Sarawut; Noisa, Parinya

    2015-03-26

    Progressively loss of neural and glial cells is the key event that leads to nervous system dysfunctions and diseases. Several neurodegenerative diseases, for instance Alzheimer's disease, Parkinson's disease, and Huntington's disease, are associated to aging and suggested to be a consequence of deficiency of neural stem cell pool in the affected brain regions. Endogenous neural stem cells exist throughout life and are found in specific niches of human brain. These neural stem cells are responsible for the regeneration of new neurons to restore, in the normal circumstance, the functions of the brain. Endogenous neural stem cells can be isolated, propagated, and, notably, differentiated to most cell types of the brain. On the other hand, other types of stem cells, such as mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells can also serve as a source for neural stem cell production, that hold a great promise for regeneration of the brain. The replacement of neural stem cells, either endogenous or stem cell-derived neural stem cells, into impaired brain is highly expected as a possible therapeutic mean for neurodegenerative diseases. In this review, clinical features and current routinely treatments of age-related neurodegenerative diseases are documented. Noteworthy, we presented the promising evidence of neural stem cells and their derivatives in curing such diseases, together with the remaining challenges to achieve the best outcome for patients.

  1. Dynamics of climate-based malaria transmission model with age-structured human population

    Science.gov (United States)

    Addawe, Joel; Pajimola, Aprimelle Kris

    2016-10-01

    In this paper, we proposed to study the dynamics of malaria transmission with periodic birth rate of the vector and an age-structure for the human population. The human population is divided into two compartments: pre-school (0-5 years) and the rest of the human population. We showed the existence of a disease-free equilibrium point. Using published epidemiological parameters, we use numerical simulations to show potential effect of climate change in the dynamics of age-structured malaria transmission. Numerical simulations suggest that there exists an asymptotically attractive solution that is positive and periodic.

  2. Compartmentalization of ER-Bound Chaperone Confines Protein Deposit Formation to the Aging Yeast Cell.

    Science.gov (United States)

    Saarikangas, Juha; Caudron, Fabrice; Prasad, Rupali; Moreno, David F; Bolognesi, Alessio; Aldea, Martí; Barral, Yves

    2017-03-20

    In order to produce rejuvenated daughters, dividing budding yeast cells confine aging factors, including protein aggregates, to the aging mother cell. The asymmetric inheritance of these protein deposits is mediated by organelle and cytoskeletal attachment and by cell geometry. Yet it remains unclear how deposit formation is restricted to the aging lineage. Here, we show that selective membrane anchoring and the compartmentalization of the endoplasmic reticulum (ER) membrane confine protein deposit formation to aging cells during division. Supporting the idea that the age-dependent deposit forms through coalescence of smaller aggregates, two deposits rapidly merged when placed in the same cell by cell-cell fusion. The deposits localized to the ER membrane, primarily to the nuclear envelope (NE). Strikingly, weakening the diffusion barriers that separate the ER membrane into mother and bud compartments caused premature formation of deposits in the daughter cells. Detachment of the Hsp40 protein Ydj1 from the ER membrane elicited a similar phenotype, suggesting that the diffusion barriers and farnesylated Ydj1 functioned together to confine protein deposit formation to mother cells during division. Accordingly, fluorescence correlation spectroscopy measurements in dividing cells indicated that a slow-diffusing, possibly client-bound Ydj1 fraction was asymmetrically enriched in the mother compartment. This asymmetric distribution depended on Ydj1 farnesylation and intact diffusion barriers. Taking these findings together, we propose that ER-anchored Ydj1 binds deposit precursors and prevents them from spreading into daughter cells during division by subjecting them to the ER diffusion barriers. This ensures that the coalescence of precursors into a single deposit is restricted to the aging lineage.

  3. Therapeutics with SPION-labeled stem cells for the main diseases related to brain aging: a systematic review

    Directory of Open Access Journals (Sweden)

    Alvarim LT

    2014-08-01

    Full Text Available Larissa T Alvarim,1,3,* Leopoldo P Nucci,2,* Javier B Mamani,1 Luciana C Marti,1 Marina F Aguiar,1,2 Helio R Silva,1,3 Gisele S Silva,1 Mariana P Nucci-da-Silva,4 Elaine A DelBel,5,6 Lionel F Gamarra1–31Hospital Israelita Albert Einstein, São Paulo, Brazil; 2Universidade Federal de São Paulo, UNIFESP, São Paulo, Brazil; 3Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, Brazil; 4Departamento de Radiologia, Hospital das Clínicas, Universidade de São Paulo, Brazil; 5Universidade de São Paulo-Faculdade de Odontologia de Ribeirão Preto, São Paulo, Brazil; 6NAPNA- Núcleo de Apoio a Pesquisa em Neurociências Aplicadas, São Paulo, Brazil*These authors contributed equally to this workAbstract: The increase in clinical trials assessing the efficacy of cell therapy for structural and functional regeneration of the nervous system in diseases related to the aging brain is well known. However, the results are inconclusive as to the best cell type to be used or the best methodology for the homing of these stem cells. This systematic review analyzed published data on SPION (superparamagnetic iron oxide nanoparticle-labeled stem cells as a therapy for brain diseases, such as ischemic stroke, Parkinson’s disease, amyotrophic lateral sclerosis, and dementia. This review highlights the therapeutic role of stem cells in reversing the aging process and the pathophysiology of brain aging, as well as emphasizing nanotechnology as an important tool to monitor stem cell migration in affected regions of the brain.Keywords: iron oxide, dementia, stem cell, stroke, Parkinson’s disease, sclerosis disease, brain aging

  4. Derivation and growth characteristics of dental pulp stem cells from patients of different ages.

    Science.gov (United States)

    Wu, Wei; Zhou, Jian; Xu, Chong-Tao; Zhang, Jie; Jin, Yan-Jiao; Sun, Geng-Lin

    2015-10-01

    The dental pulp contains a relatively low number of stem cells; however, it is considered to be a promising source of stem cells for use in regenerative therapy. To date, it has remained elusive whether there are certain differences in the dental pulp stem cells (DPSCs) from donors of different ages. In the present study, DPSC lines were derived using teeth from children, adolescents, adults and aged donors. The derivation efficiency, the proliferative and apoptotic rate, cell marker expression and the differentiation capacity were investigated and compared among these DPSC lines. The derivation efficacy was decreased with increasing donor age. Although a large part of cell surface markers was expressed in all DPSC lines, the expression of CD29 was downregulated in the DPSCs from aged teeth. In addition, the doubling time of DPSCs from aged teeth was prolonged and the number of apoptotic cells was increased with the propagation. These DPSCs were able to differentiate into a neuronal linage, which positively expressed the neuron-specific class III beta-tubulin and microtubule‑associated protein 2, as well as into an osteogenic lineage, which positively expressed CD45; however, these DPSCs from aged teeth were completely or partially deprived of differentiation capacity. By contrast, DPSCs from younger teeth displayed significantly higher vitality and a higher potential for use in dental regenerative medicine.

  5. Stem cell therapies in preclinical models of stroke associated with aging

    Directory of Open Access Journals (Sweden)

    Aurel ePopa-Wagner

    2014-11-01

    Full Text Available Stroke has limited treatment options, demanding a vigorous search for new therapeutic strategies. Initial enthusiasm to stimulate restorative processes in the ischemic brain by means of cell-based therapies has meanwhile converted into a more balanced view recognizing impediments related to unfavorable environments that are in part related to aging processes. Since stroke afflicts mostly the elderly, it is highly desirable and clinically important to test the efficacy of cell therapies in aged brain microenvironments. Although widely believed to be refractory to regeneration, recent studies using both neural precursor cells and bone marrow-derived mesenchymal stem cells for stroke therapy suggest that the aged rat brain is not refractory to cell-based therapy, and that it also supports plasticity and remodeling. Yet, important differences exist in the aged compared with young brain, i.e., the accelerated progression of ischemic injury to brain infarction, the reduced rate of endogenous neurogenesis and the delayed initiation of neurological recovery. Pitfalls in the development of cell-based therapies may also be related to age-associated comorbidities, e.g., diabetes or hyperlipidemia, which may result in maladaptive or compromised brain remodeling, respectively. These age-related aspects should be carefully considered in the clinical translation of restorative therapies.

  6. The impact of age on oncogenic potential: tumor-initiating cells and the brain microenvironment.

    Science.gov (United States)

    Stoll, Elizabeth A; Horner, Philip J; Rostomily, Robert C

    2013-10-01

    Paradoxically, aging leads to both decreased regenerative capacity in the brain and an increased risk of tumorigenesis, particularly the most common adult-onset brain tumor, glioma. A shared factor contributing to both phenomena is thought to be age-related alterations in neural progenitor cells (NPCs), which function normally to produce new neurons and glia, but are also considered likely cells of origin for malignant glioma. Upon oncogenic transformation, cells acquire characteristics known as the hallmarks of cancer, including unlimited replication, altered responses to growth and anti-growth factors, increased capacity for angiogenesis, potential for invasion, genetic instability, apoptotic evasion, escape from immune surveillance, and an adaptive metabolic phenotype. The precise molecular pathogenesis and temporal acquisition of these malignant characteristics is largely a mystery. Recent studies characterizing NPCs during normal aging, however, have begun to elucidate mechanisms underlying the age-associated increase in their malignant potential. Aging cells are dependent upon multiple compensatory pathways to maintain cell cycle control, normal niche interactions, genetic stability, programmed cell death, and oxidative metabolism. A few multi-functional proteins act as 'critical nodes' in the coordination of these various cellular activities, although both intracellular signaling and elements within the brain environment are critical to maintaining a balance between senescence and tumorigenesis. Here, we provide an overview of recent progress in our understanding of how mechanisms underlying cellular aging inform on glioma pathogenesis and malignancy.

  7. Influence of aging on the quantity and quality of human cardiac stem cells

    Science.gov (United States)

    Nakamura, Tamami; Hosoyama, Tohru; Kawamura, Daichi; Takeuchi, Yuriko; Tanaka, Yuya; Samura, Makoto; Ueno, Koji; Nishimoto, Arata; Kurazumi, Hiroshi; Suzuki, Ryo; Ito, Hiroshi; Sakata, Kensuke; Mikamo, Akihito; Li, Tao-Sheng; Hamano, Kimikazu

    2016-01-01

    Advanced age affects various tissue-specific stem cells and decreases their regenerative ability. We therefore examined whether aging affected the quantity and quality of cardiac stem cells using cells obtained from 26 patients of various ages (from 2 to 83 years old). We collected fresh right atria and cultured cardiosphere-derived cells (CDCs), which are a type of cardiac stem cell. Then we investigated growth rate, senescence, DNA damage, and the growth factor production of CDCs. All samples yielded a sufficient number of CDCs for experiments and the cellular growth rate was not obviously associated with age. The expression of senescence-associated b-galactosidase and the DNA damage marker, gH2AX, showed a slightly higher trend in CDCs from older patients (≥65 years). The expression of VEGF, HGF, IGF-1, SDF-1, and TGF-b varied among samples, and the expression of these beneficial factors did not decrease with age. An in vitro angiogenesis assay also showed that the angiogenic potency of CDCs was not impaired, even in those from older patients. Our data suggest that the impact of age on the quantity and quality of CDCs is quite limited. These findings have important clinical implications for autologous stem cell transplantation in elderly patients. PMID:26947751

  8. Cytochrome c oxidase loses catalytic activity and structural integrity during the aging process in Drosophila melanogaster

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Jian-Ching; Rebrin, Igor [Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033 (United States); Klichko, Vladimir; Orr, William C. [Department of Biological Sciences, Southern Methodist University, Dallas, TX 75275 (United States); Sohal, Rajindar S., E-mail: sohal@usc.edu [Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033 (United States)

    2010-10-08

    Research highlights: {yields} Cytochrome c oxidase loses catalytic activity during the aging process. {yields} Abundance of seven nuclear-encoded subunits of cytochrome c oxidase decreased with age in Drosophila. {yields} Cytochrome c oxidase is specific intra-mitochondrial site of age-related deterioration. -- Abstract: The hypothesis, that structural deterioration of cytochrome c oxidase (CcO) is a causal factor in the age-related decline in mitochondrial respiratory activity and an increase in H{sub 2}O{sub 2} generation, was tested in Drosophila melanogaster. CcO activity and the levels of seven different nuclear DNA-encoded CcO subunits were determined at three different stages of adult life, namely, young-, middle-, and old-age. CcO activity declined progressively with age by 33%. Western blot analysis, using antibodies specific to Drosophila CcO subunits IV, Va, Vb, VIb, VIc, VIIc, and VIII, indicated that the abundance these polypeptides decreased, ranging from 11% to 40%, during aging. These and previous results suggest that CcO is a specific intra-mitochondrial site of age-related deterioration, which may have a broad impact on mitochondrial physiology.

  9. Aging Optimization of Aluminum-Lithium Alloy L277 for Application to Cryotank Structures

    Science.gov (United States)

    Sova, B. J.; Sankaran, K. K.; Babel, H.; Farahmand, B.; Cho, A.

    2003-01-01

    Compared with aluminum alloys such as 2219, which is widely used in space vehicle for cryogenic tanks and unpressurized structures, aluminum-lithium alloys possess attractive combinations of lower density and higher modulus along with comparable mechanical properties and improved damage tolerance. These characteristics have resulted in the successful use of the aluminum-lithium alloy 2195 for the Space Shuttle External Tank, and the consideration of newer U.S. aluminum-lithium alloys such as L277 and C458 for future space vehicles. A design of experiments aging study was conducted for plate and a limited study on extrusions. To achieve the T8 temper, Alloy L277 is typically aged at 290 F for 40 hours. In the study for plate, a two-step aging treatment was developed through a design of experiments study and the one step aging used as a control. Based on the earlier NASA studies on 2195, the first step aging temperature was varied between 220 F and 260 F. The second step aging temperatures was varied between 290 F and 310 F, which is in the range of the single-step aging temperature. For extrusions, two, single-step, and one two-step aging condition were evaluated. The results of the design of experiments used for the T8 temper as well as a smaller set of experiments for the T6 temper for plate and the results for extrusions will be presented.

  10. A synthetic circuit for selectively arresting daughter cells to create aging populations.

    Science.gov (United States)

    Afonso, Bruno; Silver, Pamela A; Ajo-Franklin, Caroline M

    2010-05-01

    The ability to engineer genetic programs governing cell fate will permit new safeguards for engineered organisms and will further the biological understanding of differentiation and aging. Here, we have designed, built and implemented a genetic device in the budding yeast Saccharomyces cerevisiae that controls cell-cycle progression selectively in daughter cells. The synthetic device was built in a modular fashion by combining timing elements that are coupled to the cell cycle, i.e. cell-cycle specific promoters and protein degradation domains, and an enzymatic domain which conditionally confers cell arrest. Thus, in the presence of a drug, the device is designed to arrest growth of only newly-divided daughter cells in the population. Indeed, while the engineered cells grow normally in the absence of drug, with the drug the engineered cells display reduced, linear growth on the population level. Fluorescence microscopy of single cells shows that the device induces cell arrest exclusively in daughter cells and radically shifts the age distribution of the resulting population towards older cells. This device, termed the 'daughter arrester', provides a blueprint for more advanced devices that mimic developmental processes by having control over cell growth and death.

  11. Age and gender effects on DNA strand break repair in peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Garm, Christian; Moreno-Villanueva, Maria; Bürkle, Alexander;

    2013-01-01

    single-strand breaks (SSBs) and double-strand breaks (DSBs) in human peripheral blood mononuclear cells (PBMCs). Of these lesions, DSBs are the least frequent but the most dangerous for cells. We have measured the level of endogenous SSBs, SSB repair capacity, γ-H2AX response, and DSB repair capacity...... in a study population consisting of 216 individuals from a population-based sample of twins aged 40-77 years. Age in this range did not seem to have any effect on the SSB parameters. However, γ-H2AX response and DSB repair capacity decreased with increasing age, although the associations did not reach...

  12. Age-associated Epstein–Barr virus-specific T cell responses in seropositive healthy adults

    Science.gov (United States)

    Cárdenas Sierra, D; Vélez Colmenares, G; Orfao de Matos, A; Fiorentino Gómez, S; Quijano Gómez, S M

    2014-01-01

    Epstein–Barr virus (EBV) is present in 95% of the world's adult population. The immune response participates in immune vigilance and persistent infection control, and this condition is maintained by both a good quality (functionality) and quantity of specific T cells throughout life. In the present study, we evaluated EBV-specific CD4+ and CD8+ T lymphocyte responses in seropositive healthy individuals younger and older than 50 years of age. The assessment comprised the frequency, phenotype, functionality and clonotypic distribution of T lymphocytes. We found that in both age groups a similar EBV-specific T cell response was found, with overlapping numbers of tumour necrosis factor (TNF)-α+ T lymphocytes (CD4+ and CD8+) within the memory and effector cell compartments, in addition to monofunctional and multi-functional T cells producing interleukin (IL)-2 and/or interferon (IFN)-γ. However, individuals aged more than 50 years showed significantly higher frequencies of IL-2-producing CD4+ T lymphocytes in association with greater production of soluble IFN-γ, TNF-α and IL-6 than subjects younger than 50 years. A polyclonal T cell receptor (TCR)-variable beta region (Vβ) repertoire exists in both age groups under basal conditions and in response to EBV; the major TCR families found in TNF-α+/CD4+ T lymphocytes were Vβ1, Vβ2, Vβ17 and Vβ22 in both age groups, and the major TCR family in TNF-α+/CD8+ T cells was Vβ13·1 for individuals younger than 50 years and Vβ9 for individuals aged more than 50 years. Our findings suggest that the EBV-specific T cell response (using a polyclonal stimulation model) is distributed throughout several T cell differentiation compartments in an age-independent manner and includes both monofunctional and multi-functional T lymphocytes. PMID:24666437

  13. L-carnitine significantly decreased aging of rat adipose tissue-derived mesenchymal stem cells.

    Science.gov (United States)

    Mobarak, Halimeh; Fathi, Ezzatollah; Farahzadi, Raheleh; Zarghami, Nosratollah; Javanmardi, Sara

    2017-03-01

    Mesenchymal stem cells are undifferentiated cells that have the ability to divide continuously and tissue regeneration potential during the transplantation. Aging and loss of cell survival, is one of the main problems in cell therapy. Since the production of free radicals in the aging process is effective, the use of antioxidant compounds can help in scavenging free radicals and prevent the aging of cells. The aim of this study is evaluate the effects of L-carnitine (LC) on proliferation and aging of rat adipose tissue-derived mesenchymal stem cells (rADSC). rADSCs were isolated from inguinal region of 5 male Rattus rats. Oil red-O, alizarin red-S and toluidine blue staining were performed to evaluate the adipogenic, osteogenic and chondrogenic differentiation of rADSCs, respectively. Flow cytometric analysis was done for investigating the cell surface markers. The methyl thiazol tetrazolium (MTT) method was used to determine the cell proliferation of rADSCs following exposure to different concentrations of LC. rADSCs aging was evaluated by beta-galactosidase staining. The results showed significant proliferation of rADSCs 48 h after treatment with concentrations of 0.2 mM LC. In addition, in the presence of 0.2 mM LC, rADSCs appeared to be growing faster than control group and 0.2 mM LC supplementation could significantly decrease the population doubling time and aging of rADSCs. It seems that LC would be a good antioxidant to improve lifespan of rADSCs due to the decrease in aging.

  14. Age intrinsic loss of telomere protection via TRF1 reduction in endothelial cells.

    Science.gov (United States)

    Hohensinner, P J; Kaun, C; Buchberger, E; Ebenbauer, B; Demyanets, S; Huk, I; Eppel, W; Maurer, G; Huber, K; Wojta, J

    2016-02-01

    Aging is a major factor predisposing for multiple diseases. Telomeres at the ends of chromosomes protect the integrity of chromosomal DNA. A specialized six-protein complex termed shelterin protects the telomere from unwanted interaction with DNA damage pathways. The aim of our study was to evaluate the integrity of telomeres and the stability of telomere protection during aging in endothelial cells (EC). We describe that aging EC can be characterized by an increased cell size (40%, p=0.02) and increased expression of PAI 1 (4 fold, p=0.02), MCP1 (10 fold, p=0.001) and GMCSF (15 fold, p=0.004). Telomeric state in aging cells is defined by an increased telomere oxidation (27%, p=0.01), reduced telomere length (62%, p=0.02), and increased DNA damage foci formation (5% in young EC versus 16% in aged EC, p=0.003). This telomeric dysfunction is accompanied by a reduction in the shelterin component TRF1 (33% mRNA, p=0.001; 24% protein, p=0.007). Overexpression of TRF1 in aging EC reduced telomere-associated DNA damage foci to 5% (p=0.02) and reduced expression levels of MCP1 (18% reduction, p=0.008). Aged EC have increased telomere damage and an intrinsic loss of telomere protection. Reestablishing telomere integrity could therefore be a target for rejuvenating endothelial cell function.

  15. Stratification of yeast cells during chronological aging by size points to the role of trehalose in cell vitality.

    Science.gov (United States)

    Svenkrtova, Andrea; Belicova, Lenka; Volejnikova, Andrea; Sigler, Karel; Jazwinski, S Michal; Pichova, Alena

    2016-04-01

    Cells of the budding yeast Saccharomyces cerevisiae undergo a process akin to differentiation during prolonged culture without medium replenishment. Various methods have been used to separate and determine the potential role and fate of the different cell species. We have stratified chronologically-aged yeast cultures into cells of different sizes, using centrifugal elutriation, and characterized these subpopulations physiologically. We distinguish two extreme cell types, very small (XS) and very large (L) cells. L cells display higher viability based on two separate criteria. They respire much more actively, but produce lower levels of reactive oxygen species (ROS). L cells are capable of dividing, albeit slowly, giving rise to XS cells which do not divide. L cells are more resistant to osmotic stress and they have higher trehalose content, a storage carbohydrate often connected to stress resistance. Depletion of trehalose by deletion of TPS2 does not affect the vital characteristics of L cells, but it improves some of these characteristics in XS cells. Therefore, we propose that the response of L and XS cells to the trehalose produced in the former differs in a way that lowers the vitality of the latter. We compare our XS- and L-fraction cell characteristics with those of cells isolated from stationary cultures by others based on density. This comparison suggests that the cells have some similarities but also differences that may prove useful in addressing whether it is the segregation or the response to trehalose that may play the predominant role in cell division from stationary culture.

  16. Age structure and development in ASEAN and Japan: 1950-2015; a preliminary report.

    Science.gov (United States)

    Campbell, B O

    1982-01-01

    An attempt was made to show that significant shifts in age composition have occurred and will occur in the ASEAN countries and Japan. Based on the key ratio, the ratio of the entering labor force population, 15-29, to the established labor force population, 30-64, and on the education and dependency burdence, the evidence supports that such shifts have occurred and will occur. Another goal was to trace the potential impact of these age structure changes on the economy and society of the ASEAN countries and Japan, assuming a set of hypothetical relations between age structure changes, as measured by the key ratio and various demographic, economic, and social outcomes. This was done for Indonesia, and the Indonesian "case study" suggests that past and future changes in age strucute could have led and could lead to wide swings or long waves in per capita incomes or the growth rate in per capita incomes, the skill and possible captial intensity of production, household formation rates, emigration and immigration rates, fertility rates, and suicide rates, and other indicators of social instability. Interesting conclusions also emerged from the analysis of education and dependency burdens, especially the inverse relation between Japan's and ASEAN's burdens on both indices. The low educational and dependency burdens Japan enjoyed must have given Japan a distinct advantage in providing resources for infrastrucute, plant, and equipment, and so forth--an advantage that Japan will maintain (joined by Singapore) over the rest of this century. It is entirely possible that the relative economic performance of Japan versus the ASEAN countries or the ASEAN countries versus one another could not be fully explained or adequately forecasted without considering the impact of age structure and changes in age structure. It seems unlikely that the past or future performance of these countries individually can be adequately understood or forecasted without considering the long swing

  17. A hierarchical kinetic theory of birth, death, and fission in age-structured interacting populations

    CERN Document Server

    Chou, Tom

    2015-01-01

    We study mathematical models describing the evolution of stochastic age-structured populations. After reviewing existing approaches, we present a full kinetic framework for age-structured interacting populations undergoing birth, death and fission processes, in spatially dependent environments. We define the complete probability density for the population-size-age-chart and find results under specific conditions. Connections with more classical models are also explicitly derived. In particular, we show that factorial moments for non-interacting processes are described by a natural generalization of the McKendrick-von Foerster equation, which describes mean-field deterministic behaviour. Our approach utilizes mixed type, multi-dimensional probability distributions similar to those employed in the study of gas kinetics, with terms that satisfy BBGKY-like equation hierarchies.

  18. Spring hunting of European roe deer in Vojvodina: Age structure and trophy value

    Directory of Open Access Journals (Sweden)

    Gačić Dragan

    2005-01-01

    Full Text Available Trophies of the European roe deer are the main source of income in Vojvodina hunting grounds managed by hunting associations. The specificity of site conditions (agro-biotope aggravates the hunting, especially regarding the assessment of the age and trophy value, so the best males are hunted before they reach the culmination of trophy development. The aim of this study is to define reliably the age of males in spring hunting and to analyze their trophy structure. The study results show that, in the majority of the study hunting grounds, spring (May hunting was performed correctly and professionally, and the age structure and trophy value of the males were very favorable. The males that are considered as mature for shooting account for one half of the total spring hunting, while their percentage is even higher in the so-called "trophy hunting" (60.7%, which results in a high percentage of trophies in medals (21.5%.

  19. A Hierarchical Kinetic Theory of Birth, Death and Fission in Age-Structured Interacting Populations

    Science.gov (United States)

    Chou, Tom; Greenman, Chris D.

    2016-07-01

    We develop mathematical models describing the evolution of stochastic age-structured populations. After reviewing existing approaches, we formulate a complete kinetic framework for age-structured interacting populations undergoing birth, death and fission processes in spatially dependent environments. We define the full probability density for the population-size age chart and find results under specific conditions. Connections with more classical models are also explicitly derived. In particular, we show that factorial moments for non-interacting processes are described by a natural generalization of the McKendrick-von Foerster equation, which describes mean-field deterministic behavior. Our approach utilizes mixed-type, multidimensional probability distributions similar to those employed in the study of gas kinetics and with terms that satisfy BBGKY-like equation hierarchies.

  20. [Age structure and dynamics of Quercus wutaishanica population in Lingkong Mountain of Shanxi Province, China].

    Science.gov (United States)

    Zhang, Jie; Shangguan, Tie-Liang; Duan, Yi-Hao; Guo, Wei; Liu, Wei-Hua; Guo, Dong-Gang

    2014-11-01

    Using the plant survivorship theory, the age structure, and the relationship between tree height and diameter (DBH) of Quercus wutaishanica population in Lingkong Mountain were analyzed, and the static life table was compiled and the survival curve plotted. The shuttle shape in age structure of Q. wutaishanica population suggested its temporal stability. The linear regression significantly fitted the positive correlation between tree height and DBH. The maximal life expectancy was observed among the trees beyond the age of the highest mortality and coincided with the lowest point of mortality density, suggesting the strong vitality of the seedlings and young trees that survived in the natural selection and intraspecific competition. The population stability of the Q. wutaishanica population was characterized by the Deevey-II of the survival curve. The dynamic pattern was characterized by the recession in the early phase, growth in the intermediate phase, and stability in the latter phase.

  1. EXISTENCE AND UNIQUENESS OF ENDEMIC STATES FOR THE AGE-STRUCTURED SEIR EPIDEMIC MODEL

    Institute of Scientific and Technical Information of China (English)

    Xuezhi LI; Jing CHEN

    2006-01-01

    An age-structured SEIR epidemic model of a vertically as well as horizontally transmitted disease is investigated. Threshold results for the existence of endemic states are established for most cases. Under certain conditions, uniqueness is also shown. Threshold used are explicitly computable in term of demographic and epidemiological parameters of the model.

  2. Microvascular changes in estrogen-alpha sensitive brainstem structures of aging female hamsters

    NARCIS (Netherlands)

    Gerrits, Peter O.; de Weerd, Henk; van der Want, Johannes J. L.; Kortekaas, Rudie; Luiten, Paul G. M.; Veening, Jan G.

    2010-01-01

    Structural neuronal plasticity is present in the nucleus para-retroambiguus (NPRA) and the commissural nucleus of the solitary tract/A2 group (NTScom/A2) in female hamsters. Both brainstem nuclei play a role in estrous cycle related autonomic adaptations. We investigated how aging affects the capill

  3. Interactions between shoot age structure, nutrient availability and integration in the giant bamboo Phyllostachys pubescens

    NARCIS (Netherlands)

    Li, R.; Werger, M.J.A.; Kroon, de H.; During, H.J.; Zhong, Z.C.

    2000-01-01

    The age structure of adult shoots, the nutrient availability of the habitat, and their interaction, are important factors influencing the productivity of bamboo groves. In a field fertilization experiment over two years we examined the impact of physiological integration on the emergence, growth, an

  4. Structural, biochemical, cellular, and functional changes in skeletal muscle extracellular matrix with aging

    DEFF Research Database (Denmark)

    Kragstrup, Tue Wenzel; Kjaer, M; Mackey, A L

    2011-01-01

    The extracellular matrix (ECM) of skeletal muscle is critical for force transmission and for the passive elastic response of skeletal muscle. Structural, biochemical, cellular, and functional changes in skeletal muscle ECM contribute to the deterioration in muscle mechanical properties with aging...

  5. Socio-Demographic Determinants of Economic Growth: Age-Structure, Preindustrial Heritage and Sociolinguistic Integration

    Science.gov (United States)

    Crenshaw, Edward; Robison, Kristopher

    2010-01-01

    This study establishes a socio-demographic theory of international development derived from selected classical and contemporary sociological theories. Four hypotheses are tested: (1. population growth's effect on development depends on age-structure; (2. historic population density (used here as an indicator of preindustrial social complexity)…

  6. Developmental Trajectories of Structural and Pragmatic Language Skills in School-Aged Children with Williams Syndrome

    Science.gov (United States)

    Van Den Heuvel, E.; Manders, E.; Swillen, A.; Zink, I.

    2016-01-01

    Background: This study aimed to compare developmental courses of structural and pragmatic language skills in school-aged children with Williams syndrome (WS) and children with idiopathic intellectual disability (IID). Comparison of these language trajectories could highlight syndrome-specific developmental features. Method: Twelve monolingual…

  7. Cell fine structure and function - Past and present

    Science.gov (United States)

    Fernandez-Moran, H.

    1970-01-01

    Electron microscopic studies of nerve membrane fine structure, discussing cell membrane multienzyme and macromolecular energy and information transduction, protein synthesis and nucleic acids interrelations

  8. When aging reaches CD4+ T-cells: phenotypic and functional changes

    Directory of Open Access Journals (Sweden)

    Marco Antonio Moro-García

    2013-05-01

    Full Text Available Beyond midlife, the immune system shows aging features and its defensive capability becomes impaired, by a process known as immunosenescence that involves many changes in the innate and adaptive responses. Innate immunity seems to be better preserved globally, while the adaptive immune response exhibits profound age-dependent modifications. Elderly people display a decline in numbers of naïve T-cells in peripheral blood and lymphoid tissues, while, in contrast, their proportion of highly differentiated effector and memory T-cells, such as the CD28null T-cells, increases markedly. Naïve and memory CD4+ T-cells constitute a highly dynamic system with constant homeostatic and antigen-driven proliferation, influx, and loss of T-cells. Thymic activity dwindles with age and essentially ceases in the later decades of life, severely constraining the generation of new T-cells. Homeostatic control mechanisms are very effective at maintaining a large and diverse subset of naïve CD4+ T-cells throughout life, but although later than in CD8+T-cell compartment, these mechanisms ultimately fail with age.

  9. Fibroblast growth factors as regulators of stem cell self-renewal and aging

    NARCIS (Netherlands)

    Yeoh, Joyce S. G.; de Haan, Gerald

    2007-01-01

    Organ and tissue dysfunction which is readily observable during aging results from a loss of cellular homeostasis and reduced stem cell self-renewal. Over the past 10 years, studies have been aimed at delineating growth factors that will sustain and promote the self-renewal potential of stem cells a

  10. Chronic stress induces ageing-associated degeneration in rat Leydig cells

    Institute of Scientific and Technical Information of China (English)

    Fei-Fei Wang; Qian Wang; Yong Chen; Qiang Lin; Hui-Bao Gao; Ping Zhang

    2012-01-01

    Several studies have suggested that stress and ageing exert inhibitory effects on rat Leydig cells.In a pattern similar to the normal process of Leydig cell ageing,stress-mediated increases in glucocorticoid levels inhibit steroidogenic enzyme expression that then results in decreased testosterone secretion.We hypothesized that chronic stress accelerates the degenerative changes associated with ageing in Leydig cells.To test this hypothesis,we established a model of chronic stress to evaluate stress-induced morphological and functional alterations in Brown Norway rat Leydig cells; additionally,intracellular lipofuscin levels,reactive oxygen species (ROS)levels and DNA damage were assessed.The results showed that chronic stress accelerated ageing-related changes:ultrastructural alterations associated with ageing,cellular lipofuscin accumulation,increased ROS levels and more extensive DNA damage were observed.Additionally,testosterone levels were decreased.This study sheds new light on the idea that chronic stress contributes to the degenerative changes associated with ageing in rat Leydig cells in vivo.

  11. Impact of age on the efficacy of bone marrow mononuclear cell transplantation in experimental stroke

    Directory of Open Access Journals (Sweden)

    Wagner Daniel-Christoph

    2012-08-01

    Full Text Available Abstract Bone marrow-derived mononuclear cells (BM MNC have been effectively used to treat experimental stroke. Most of the preclinical trials have been performed in young and healthy laboratory animals, even though age and hypertension are major risk factors for stroke. To determine the influence of age on the properties of BM MNCs after cerebral ischemia, we compared the efficacy of aged and young BM MNC in an in vitro model of cerebral hypoxia and in an adapted in vivo model of stroke. Human BM MNCs were obtained from healthy young or aged donors and either co-cultured with rat hippocampal slices exposed to oxygen glucose deprivation (OGD, or transplanted intravenously 24 h after permanent middle cerebral artery occlusion in aged (18 months spontaneously hypertensive rats (SHR. Efficacy was examined by quantification of hippocampal cell death, or respectively, by neurofunctional tests and MR investigations. Co-cultivation with young, but not with aged BM MNCs significantly reduced the hippocampal cell death after OGD. Transplantation of both young and old BM MNCs did not reduce functional deficits or ischemic lesion volume after stroke in aged SHR. These results suggest a significant impact of age on the therapeutic efficacy of BM MNCs after cerebral ischemia.

  12. Age-related changes in expression of the neural cell adhesion molecule in skeletal muscle

    DEFF Research Database (Denmark)

    1993-01-01

    report quantitative and qualitative changes in NCAM protein and mRNA forms during aging in normal rat skeletal muscle. Determination of the amount of NCAM by e.l.i.s.a. showed that the level decreased from perinatal to adult age, followed by a considerable increase in 24-month-old rat muscle. Thus NCAM...... virtually unchanged at all ages examined. However, changes in the extent of sialylation of NCAM were demonstrated. Even though the relative amounts of the various NCAM polypeptides were unchanged during aging, distinct changes in NCAM mRNA classes were observed. Three NCAM mRNA classes of 6.7, 5.2 and 2......Neural cell adhesion molecule (NCAM) is expressed by muscle and involved in muscle-neuron and muscle-muscle cell interactions. The expression in muscle is regulated during myogenesis and by the state of innervation. In aged muscle, both neurogenic and myogenic degenerative processes occur. We here...

  13. Safety and efficacy of vismodegib in patients aged ≥65 years with advanced basal cell carcinoma.

    Science.gov (United States)

    Chang, Anne Lynn S; Lewis, Karl D; Arron, Sarah T; Migden, Michael R; Solomon, James A; Yoo, Simon; Day, Bann-Mo; McKenna, Edward F; Sekulic, Aleksandar

    2016-11-15

    Because many patients with unresectable basal cell carcinoma (BCC) are aged ≥65 years, this study explores the efficacy and safety of vismodegib in these patients with locally advanced (la) or metastatic (m) basal cell carcinoma (BCC) in the ERIVANCE BCC trial and the expanded access study (EAS).We compared patients aged ≥65 years to patients aged vismodegib 150 mg/day, using descriptive statistics for response and safety. Patients aged ≥65 years (laBCC/mBCC) were enrolled in ERIVANCE BCC (33/14) and EAS (27/26). Investigator-assessed best overall response rate in patients ≥65 and Vismodegib demonstrated similar clinical activity and adverse events regardless of age.

  14. Analysis of an Age Structured SEIRS Epidemic Model with Varying Total Population Size and Vaccination

    Institute of Scientific and Technical Information of China (English)

    Xue-Zhi Li; Geni Gupur; Guang-Tian Zhu

    2004-01-01

    This article focuses on the study of an age structured SEIRS epidemic model with a vaccination program when the total population size is not kept at constant. We first give the explicit expression of the reproduction number R((ψ),(λ))in the presence of vaccine((λ))is the exponent of growth of total population), and show that the infection-free steady state is linearly stable if R ((ψ),(λ))1, then we apply the theoretical results to vaccination policies to determine the optimal age or ages at which an individual should be vaccinated. It is shown that the optimal strategy can be either one-or two-age strategies.

  15. Second quantization approaches for stochastic age-structured birth-death processes

    CERN Document Server

    Greenman, Chris D

    2015-01-01

    We develop a fully stochastic theory for age-structured populations via Doi-Peliti quantum field theoretical methods. The operator formalism of Doi is first developed, whereby birth and death events are represented by creation and annihilation operators, and the complete probabilistic representation of the age-chart of a population is represented by states in a suitable Hilbert space. We then use this formalism to rederive several results in companion paper [6], including an equation describing the moments of the age-distribution, and the distribution of the population size. The functional representation of coherent states used by Peliti to analyze discrete Fock space is then adapted to incorporate the continuous age parameters, and a path integral formulation constructed. We apply these formalisms to a range of birth-death processes and show that although many of the results from Doi-Peliti formalism can be derived in a purely probabilistic way, the efficient formalism offered by second quantization methods ...

  16. Effects of text genre and verbal ability on adult age differences in sensitivity to text structure.

    Science.gov (United States)

    Petros, T V; Norgaard, L; Olson, K; Tabor, L

    1989-06-01

    The present study examined the effects of verbal ability and text genre on adult age differences in sensitivity to the semantic structure of prose. Young and older adults of low or high verbal ability heard narrative and expository passages at different presentation rates. The results demonstrated that older adults recalled less than younger adults and that age differences in recall were larger for low-verbal adults and expository texts. However, subjects from all groups favored the main ideas in their recalls for both types of passages. The results indicated that adult age similarities in the ability to focus on the main ideas when processing prose was not compromised by the verbal ability of the subjects or the organization of the passages used. However, the results also demonstrate how the characteristics of the learner and the characteristics of the text modulate the size of the age differences observed.

  17. Sparse representation of brain aging: extracting covariance patterns from structural MRI.

    Directory of Open Access Journals (Sweden)

    Longfei Su

    Full Text Available An enhanced understanding of how normal aging alters brain structure is urgently needed for the early diagnosis and treatment of age-related mental diseases. Structural magnetic resonance imaging (MRI is a reliable technique used to detect age-related changes in the human brain. Currently, multivariate pattern analysis (MVPA enables the exploration of subtle and distributed changes of data obtained from structural MRI images. In this study, a new MVPA approach based on sparse representation has been employed to investigate the anatomical covariance patterns of normal aging. Two groups of participants (group 1:290 participants; group 2:56 participants were evaluated in this study. These two groups were scanned with two 1.5 T MRI machines. In the first group, we obtained the discriminative patterns using a t-test filter and sparse representation step. We were able to distinguish the young from old cohort with a very high accuracy using only a few voxels of the discriminative patterns (group 1:98.4%; group 2:96.4%. The experimental results showed that the selected voxels may be categorized into two components according to the two steps in the proposed method. The first component focuses on the precentral and postcentral gyri, and the caudate nucleus, which play an important role in sensorimotor tasks. The strongest volume reduction with age was observed in these clusters. The second component is mainly distributed over the cerebellum, thalamus, and right inferior frontal gyrus. These regions are not only critical nodes of the sensorimotor circuitry but also the cognitive circuitry although their volume shows a relative resilience against aging. Considering the voxels selection procedure, we suggest that the aging of the sensorimotor and cognitive brain regions identified in this study has a covarying relationship with each other.

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

    Science.gov (United States)

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

    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.

  19. Structural invariance and age-related performance differences in face cognition.

    Science.gov (United States)

    Hildebrandt, Andrea; Sommer, Werner; Herzmann, Grit; Wilhelm, Oliver

    2010-12-01

    Perceiving and memorizing faces swiftly and correctly are important social competencies. The organization of these interpersonal abilities and how they change across the life span are still poorly understood. We investigated changes in the mean and covariance structure of face cognition abilities across the adult life span. A sample of 448 participants, with age ranging from 18 to 88 years, completed a battery of 15 face cognition tasks. After establishing a measurement model of face cognition that distinguishes between face perception, face memory, and the speed of face cognition, we used multiple group models and age-weighted measurement models to explore age-related changes. The modeling showed that the loadings and intercepts of all measures are age invariant. The factor means showed substantial decrements with increasing age. Age-related decrements in performance were strongest for the speed of face cognition but were also salient for face perception and face memory. The onset of age decrements is apparent in the 60s for face perception, in the late 40s for face memory, and in the early 30s for speed of face cognition. Implications of these findings on a theoretical and methodological level are discussed, and potential consequences for applied settings are considered.

  20. The relation between structural and functional connectivity depends on age and on task goals

    Directory of Open Access Journals (Sweden)

    Jaclyn Hennessey Ford

    2014-05-01

    Full Text Available The last decade has seen an increase in neuroimaging studies examining structural (i.e., structural integrity of white matter tracts and functional connectivity (e.g., correlations in neural activity throughout the brain. Although structural and functional connectivity changes have often been measured independently, examining the relation between these two measures is critical to understanding the specific function of neural networks and the ways they may differ across tasks and individuals. The current study addressed this question by examining the effect of age (treated as a continuous variable and emotional valence on the relation between functional and structural connectivity. As prior studies have suggested that prefrontal regions may guide and regulate emotional memory search via functional connections with the amygdala, the current analysis focused on functional connectivity between the left amygdala and the left prefrontal cortex, and structural integrity of the uncinate fasciculus, a white matter tract connecting prefrontal and temporal regions.Participants took part in a scanned retrieval task in which they recalled positive, negative, and neutral images associated with neutral titles. Aging was associated with a significant increase in the relation between measures of structural integrity (specifically, fractional anisotropy, or FA along the uncinate fasciculus and functional connectivity between the left ventral prefrontal cortex and amygdala during positive event retrieval, but not negative or neutral retrieval. Notably, during negative event retrieval, age was linked to stronger structure-function relations between the amygdala and the dorsal anterior cingulate cortex, such that increased structural integrity predicted strong negative functional connectivity in older adults only. These findings are consistent with theories that older adults may engage regulatory strategies if they have the structural pathways to allow them to do so.

  1. Stromal-epithelial interactions in aging and cancer: Senescent fibroblasts alter epithelial cell differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith

    2004-07-14

    Cellular senescence suppresses cancer by arresting cells at risk for malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation, and branching morphogenesis. Further, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts--the ability to alter epithelial differentiation--that might also explain the loss of tissue function and organization that is a hallmark of aging.

  2. Accumulation of DNA damage-induced chromatin alterations in tissue-specific stem cells: the driving force of aging?

    Directory of Open Access Journals (Sweden)

    Nadine Schuler

    Full Text Available Accumulation of DNA damage leading to stem cell exhaustion has been proposed to be a principal mechanism of aging. Using 53BP1-foci as a marker for DNA double-strand breaks (DSBs, hair follicle stem cells (HFSCs in mouse epidermis were analyzed for age-related DNA damage response (DDR. We observed increasing amounts of 53BP1-foci during the natural aging process independent of telomere shortening and after protracted low-dose radiation, suggesting substantial accumulation of DSBs in HFSCs. Electron microscopy combined with immunogold-labeling showed multiple small 53BP1 clusters diffusely distributed throughout the highly compacted heterochromatin of aged HFSCs, but single large 53BP1 clusters in irradiated HFSCs. These remaining 53BP1 clusters did not colocalize with core components of non-homologous end-joining, but with heterochromatic histone modifications. Based on these results we hypothesize that these lesions were not persistently unrepaired DSBs, but may reflect chromatin rearrangements caused by the repair or misrepair of DSBs. Flow cytometry showed increased activation of repair proteins and damage-induced chromatin modifications, triggering apoptosis and cellular senescence in irradiated, but not in aged HFSCs. These results suggest that accumulation of DNA damage-induced chromatin alterations, whose structural dimensions reflect the complexity of the initial genotoxic insult, may lead to different DDR events, ultimately determining the biological outcome of HFSCs. Collectively, our findings support the hypothesis that aging might be largely the remit of structural changes to chromatin potentially leading to epigenetically induced transcriptional deregulation.

  3. An artificial intelligence-based structural health monitoring system for aging aircraft

    Science.gov (United States)

    Grady, Joseph E.; Tang, Stanley S.; Chen, K. L.

    1993-01-01

    To reduce operating expenses, airlines are now using the existing fleets of commercial aircraft well beyond their originally anticipated service lives. The repair and maintenance of these 'aging aircraft' has therefore become a critical safety issue, both to the airlines and the Federal Aviation Administration. This paper presents the results of an innovative research program to develop a structural monitoring system that will be used to evaluate the integrity of in-service aerospace structural components. Currently in the final phase of its development, this monitoring system will indicate when repair or maintenance of a damaged structural component is necessary.

  4. Single cell analysis of yeast replicative aging using a new generation of microfluidic device.

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    Full Text Available A major limitation to yeast aging study has been the inability to track mother cells and observe molecular markers during the aging process. The traditional lifespan assay relies on manual micro-manipulation to remove daughter cells from the mother, which is laborious, time consuming, and does not allow long term tracking with high resolution microscopy. Recently, we have developed a microfluidic system capable of retaining mother cells in the microfluidic chambers while removing daughter cells automatically, making it possible to observe fluorescent reporters in single cells throughout their lifespan. Here we report the development of a new generation of microfluidic device that overcomes several limitations of the previous system, making it easier to fabricate and operate, and allowing functions not possible with the previous design. The basic unit of the device consists of microfluidic channels with pensile columns that can physically trap the mother cells while allowing the removal of daughter cells automatically by the flow of the fresh media. The whole microfluidic device contains multiple independent units operating in parallel, allowing simultaneous analysis of multiple strains. Using this system, we have reproduced the lifespan curves for the known long and short-lived mutants, demonstrating the power of the device for automated lifespan measurement. Following fluorescent reporters in single mother cells throughout their lifespan, we discovered a surprising change of expression of the translation elongation factor TEF2 during aging, suggesting altered translational control in aged mother cells. Utilizing the capability of the new device to trap mother-daughter pairs, we analyzed mother-daughter inheritance and found age dependent asymmetric partitioning of a general stress response reporter between mother and daughter cells.

  5. Circadian regulation of cell cycle: Molecular connections between aging and the circadian clock.

    Science.gov (United States)

    Khapre, Rohini V; Samsa, William E; Kondratov, Roman V

    2010-09-01

    The circadian clock generates oscillations in physiology and behavior, known as circadian rhythms. Links between the circadian clock genes Periods, Bmal1, and Cryptochromes and aging and cancer are emerging. Circadian clock gene expression is changed in human pathologies, and transgenic mice with mutations in clock genes develop cancer and premature aging. Control of genome integrity and cell proliferation play key roles in the development of age-associated pathologies and carcinogenesis. Here, we review recent data on the connection between the circadian clock and control of the cell cycle. The circadian clock regulates the activity and expression of several critical cell cycle and cell cycle check-point-related proteins, and in turn cell cycle-associated proteins regulate circadian clock proteins. DNA damage can reset the circadian clock, which provides a molecular mechanism for reciprocal regulation between the circadian clock and the cell cycle. This circadian clock-dependent control of cell proliferation, together with other known physiological functions of the circadian clock such as the control of metabolism, oxidative and genotoxic stress response, and DNA repair, opens new horizons for understanding the mechanisms behind aging and carcinogenesis.

  6. Targeting senescent cells enhances adipogenesis and metabolic function in old age.

    Science.gov (United States)

    Xu, Ming; Palmer, Allyson K; Ding, Husheng; Weivoda, Megan M; Pirtskhalava, Tamar; White, Thomas A; Sepe, Anna; Johnson, Kurt O; Stout, Michael B; Giorgadze, Nino; Jensen, Michael D; LeBrasseur, Nathan K; Tchkonia, Tamar; Kirkland, James L

    2015-12-19

    Senescent cells accumulate in fat with aging. We previously found genetic clearance of senescent cells from progeroid INK-ATTAC mice prevents lipodystrophy. Here we show that primary human senescent fat progenitors secrete activin A and directly inhibit adipogenesis in non-senescent progenitors. Blocking activin A partially restored lipid accumulation and expression of key adipogenic markers in differentiating progenitors exposed to senescent cells. Mouse fat tissue activin A increased with aging. Clearing senescent cells from 18-month-old naturally-aged INK-ATTAC mice reduced circulating activin A, blunted fat loss, and enhanced adipogenic transcription factor expression within 3 weeks. JAK inhibitor suppressed senescent cell activin A production and blunted senescent cell-mediated inhibition of adipogenesis. Eight weeks-treatment with ruxolitinib, an FDA-approved JAK1/2 inhibitor, reduced circulating activin A, preserved fat mass, reduced lipotoxicity, and increased insulin sensitivity in 22-month-old mice. Our study indicates targeting senescent cells or their products may alleviate age-related dysfunction of progenitors, adipose tissue, and metabolism.

  7. Aging Optimization of Aluminum-Lithium Alloy C458 for Application to Cryotank Structures

    Science.gov (United States)

    Sova, B. J.; Sankaran, K. K.; Babel, H.; Farahmand, B.; Rioja, R.

    2003-01-01

    Compared with aluminum alloys such as 2219, which is widely used in space vehicle for cryogenic tanks and unpressurized structures, aluminum-lithium alloys possess attractive combinations of lower density and higher modulus along with comparable mechanical properties. These characteristics have resulted in the successful use of the aluminum-lithium alloy 2195 (Al-1.0 Li-4.0 Cu-0.4 Mg-0.4 Ag-0.12 Zr) for the Space Shuttle External Tank, and the consideration of newer U.S. aluminum-lithium alloys such as L277 and C458 for future space vehicles. These newer alloys generally have lithium content less than 2 wt. % and their composition and processing have been carefully tailored to increase the toughness and reduce the mechanical property anisotropy of the earlier generation alloys such 2090 and 8090. Alloy processing, particularly the aging treatment, has a significant influence on the strength-toughness combinations and their dependence on service environments for aluminum-lithium alloys. Work at NASA Marshall Space Flight Center on alloy 2195 has shown that the cryogenic toughness can be improved by employing a two-step aging process. This is accomplished by aging at a lower temperature in the first step to suppress nucleation of the strengthening precipitate at sub-grain boundaries while promoting nucleation in the interior of the grains. Second step aging at the normal aging temperature results in precipitate growth to the optimum size. A design of experiments aging study was conducted for plate. To achieve the T8 temper, Alloy C458 (Al-1.8 Li-2.7 Cu-0.3 Mg- 0.08 Zr-0.3 Mn-0.6 Zn) is typically aged at 300 F for 24 hours. In this study, a two-step aging treatment was developed through a comprehensive 24 full factorial design of experiments study and the typical one-step aging used as a reference. Based on the higher lithium content of C458 compared with 2195, the first step aging temperature was varied between 175 F and 250 F. The second step aging temperatures was

  8. Impaired phagocytosis of apoptotic cells causes accumulation of bone marrow-derived macrophages in aged mice

    Science.gov (United States)

    Kim, Ok-Hee; Kim, Hyojung; Kang, Jinku; Yang, Dongki; Kang, Yu-Hoi; Lee, Dae Ho; Cheon, Gi Jeong; Park, Sang Chul; Oh, Byung-Chul

    2017-01-01

    Accumulation of tissue macrophages is a significant characteristic of disease-associated chronic inflammation, and facilitates the progression of disease pathology. However, the functional roles of these bone marrow-derived macrophages (BMDMs) in aging are unclear. Here, we identified age-dependent macrophage accumulation in the bone marrow, showing that aging significantly increases the number of M1 macrophages and impairs polarization of BMDMs. We found that age-related dysregulation of BMDMs is associated with abnormal overexpression of the anti-inflammatory interleukin-10. BMDM dysregulation in aging impairs the expression levels of pro-inflammatory cytokines and genes involved in B-cell maturation and activation. Phagocytosis of apoptotic Jurkat cells by BMDMs was reduced because of low expression of phagocytic receptor CD14, indicating that increased apoptotic cells may result from defective phagocytosis of apoptotic cells in the BM of aged mice. Therefore, CD14 may represent a promising target for preventing BMDM dysregulation, and macrophage accumulation may provide diagnostic and therapeutic clues. PMID:27866511

  9. Predicting the ageing and the long-term durability of organic polymer solar cells

    Science.gov (United States)

    Gardette, Jean-Luc; Rivaton, Agnès; Thérias, Sandrine; Chambon, Sylvain; Manceau, Matthieu; Gaume, Julien

    2010-06-01

    Organic solar cells based on conductive polymers exhibit a unique combination of properties which include low cost, flexibility and large surface processability. Organic photovoltaic could then prevail for some applications alongside silicon, such as nomad or indoor. To achieve this objective, the sustainability of the initial properties in conditions of use of the cell is required, since it could be a lock to the emergence of these devices in the market. The polymers used in solar cells are indeed known to exhibit low resistance to environmental constraints, in particular to the combined action of sunlight, oxygen and water. We present recent results on both the accelerated artificial and the natural outdoors ageing of MDMO-PPV (Poly[2-methoxy-5-(3',7'-dimethyloctyloxy)-1,4-Phenylenevinylene) and P3HT/PCBM blends poly(3-hexylthiophene) (P3HT) (methano-fullerene[6,6]-phenyl C61-butyric acid methyl ester) ([60] PCBM). The influence of various parameters such as the temperature and the presence of oxygen were studied. The modifications of the chemical structure of both the components of the blend were monitored by spectroscopic analysis (infrared, UV-visible), the morphology of the blends was analysed by AFM and XRD and the photovoltaic performances all along the exposure were recorded. Two important results have been pointed out: on one hand, the Achilles heel of the chemical structure of MDMO-PPV and P3HT under the impact of light has been evidenced. On the other hand, it has been shown that P3HT:PCBM blends are much more stable than MDMO:PCBM blends whatever the conditions of ageing are. Results show that a convenient encapsulation can ensure a promising lifetime of P3HT/PCBM blends in real conditions of use. This work also focuses on this last point and proposes to study and try to understand the behavior of the materials used in the active layer when submitted to photoaging and thermal aging in the absence of oxygen. To fulfil very good encapsulation, glass

  10. Predictors of coupling between structural and functional cortical networks in normal aging.

    Science.gov (United States)

    Romero-Garcia, Rafael; Atienza, Mercedes; Cantero, Jose L

    2014-06-01

    Understanding how the mammalian neocortex creates cognition largely depends on knowledge about large-scale cortical organization. Accumulated evidence has illuminated cortical substrates of cognition across the lifespan, but how topological properties of cortical networks support structure-function relationships in normal aging remains an open question. Here we investigate the role of connections (i.e., short/long and direct/indirect) and node properties (i.e., centrality and modularity) in predicting functional-structural connectivity coupling in healthy elderly subjects. Connectivity networks were derived from correlations of cortical thickness and cortical glucose consumption in resting state. Local-direct connections (i.e., nodes separated by less than 30 mm) and node modularity (i.e., a set of nodes highly interconnected within a topological community and sparsely interconnected with nodes from other modules) in the functional network were identified as the main determinants of coupling between cortical networks, suggesting that the structural network in aging is mainly constrained by functional topological properties involved in the segregation of information, likely due to aging-related deficits in functional integration. This hypothesis is supported by an enhanced connectivity between cortical regions of different resting-state networks involved in sensorimotor and memory functions in detrimental to associations between fronto-parietal regions supporting executive processes. Taken collectively, these findings open new avenues to identify aging-related failures in the anatomo-functional organization of the neocortical mantle, and might contribute to early detection of prevalent neurodegenerative conditions occurring in the late life.

  11. The effect of gender and age structure on municipal waste generation in Poland

    Energy Technology Data Exchange (ETDEWEB)

    Talalaj, Izabela Anna, E-mail: izabela.tj@gmail.com; Walery, Maria, E-mail: m.walery@pb.edu.pl

    2015-06-15

    Highlights: • An effect of gender and age structure on municipal waste generation was presented. • The waste accumulation index is influenced by a number of unemployed women. • Greater share of women in society contributes to greater waste production. • A model describing the analyzed dependences was determined. - Abstract: In this study the effect of gender and age structure on municipal waste generation was investigated. The data from 10-year period, from 2001 to 2010 year, were taken into consideration. The following parameters of gender and age structure were analyzed: men and woman quantity, female to male ratio, number of working, pre-working and post-working age men/women, number of unemployed men/women. The results have showed a strong correlation of annual per capita waste generation rate with number of unemployed women (r = 0.70) and female to male ratio (r = 0.81). This indicates that waste generation rate is more depended on ratio of men and women that on quantitative size of each group. Using the regression analysis a model describing the dependence between female to male ratio, number of unemployed woman and waste quantity was determined. The model explains 70% of waste quantity variation. Obtained results can be used both to improve waste management and to a fuller understanding of gender behavior.

  12. The evolution of alternative cryptic female choice strategies in age-structured populations.

    Science.gov (United States)

    Jones, Adam G

    2002-12-01

    Cryptic female choice is a potentially important aspect of the sexual selection process. According to the theory of sexual dialectics, postcopulation manipulation of relative male fertilization success can provide an avenue by which females can circumvent attempts by males to control female reproduction. Here I use stochastic models to investigate the evolution of cryptic female choice in populations with and without age structure. In populations without age structure, cryptic female choice will evolve only when (1) precopulatory mate choice by females is inefficient, (2) variation in male fitness is correlated with a trait upon which a female can base her choice of mates, and (3) the cost of multiple mating is not too high. In populations with age structure, similar conditions apply. However, selection sometimes favors females that employ alternative strategies of female choice at different ages. These results help to define the types of biological systems in which we should expect to see the evolution of cryptic female choice. They also illustrate that the evolution of choice strategies in females may be complex and may mirror in some important respects the evolution of alternative mating tactics in males.

  13. Relationship between the population age structure and recreational landscape: an example of Dubrava, Zagreb

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    Ivana Crljenko

    2013-12-01

    Full Text Available The starting point of this article follows a premise that demographic characteristics of a population, which constructs and consumes space on a daily basis, and cultural landscapes are interconnected, i.e. that certain demographics can be read from urban cultural landscapes in a greater or lesser extent. Of all the demographic structures incorporated in Croatian urban landscapes it is easiest to recognize the age, educational, religious, economic and ethnic/national composition, while the racial and gender structures are almost unnoticed. This paper presents the results of the analysis of the relationship between the population age structure and recreational landscapes of the eastern outskirts of Zagreb – Dubrava. By using the statistical analysis in the first part of the article, the author discusses the past and current age composition, as well as the trend of population aging. After that, the author provides descriptive and/or statistical analysis of some elements of recreational landscape in Dubrava, such as green areas, children’s and sports playgrounds, public gardens, sports centers, Grad mladih, and second homes, in order to determine the contemporary situation in the landscape. Considering the dominant process of rapid aging of the Dubrava population, a mismatch between the needs for recreation of the aged population and the real situation in the space was noticed. The lack of recreational facilities is evident not only for those intended for elderly residents, but also for the younger ones; the reasons are usually associated with the lack of financial resources, and in some cases with decision-making processes on a higher level than those of the city districts. Two subtypes of recreational landscapes were differentiated: sports and recreational landscape and second home landscape.

  14. Sparing of extraocular muscle in aging and muscular dystrophies: A myogenic precursor cell hypothesis

    Energy Technology Data Exchange (ETDEWEB)

    Kallestad, Kristen M.; Hebert, Sadie L.; McDonald, Abby A.; Daniel, Mark L.; Cu, Sharon R.; McLoon, Linda K., E-mail: mcloo001@tc.umn.edu

    2011-04-01

    The extraocular muscles (EOM) are spared from pathology in aging and many forms of muscular dystrophy. Despite many studies, this sparing remains an enigma. The EOM have a distinct embryonic lineage compared to somite-derived muscles, and we have shown that they continuously remodel throughout life, maintaining a population of activated satellite cells even in aging. These data suggested the hypothesis that there is a population of myogenic precursor cells (mpcs) in EOM that is different from those in limb, with either elevated numbers of stem cells and/or mpcs with superior proliferative capacity compared to mpcs in limb. Using flow cytometry, EOM and limb muscle mononuclear cells were compared, and a number of differences were seen. Using two different cell isolation methods, EOM have significantly more mpcs per mg muscle than limb skeletal muscle. One specific subpopulation significantly increased in EOM compared to limb was positive for CD34 and negative for Sca-1, M-cadherin, CD31, and CD45. We named these the EOMCD34 cells. Similar percentages of EOMCD34 cells were present in both newborn EOM and limb muscle. They were retained in aged EOM, whereas the population decreased significantly in adult limb muscle and were extremely scarce in aged limb muscle. Most importantly, the percentage of EOMCD34 cells was elevated in the EOM from both the mdx and the mdx/utrophin{sup -/-} (DKO) mouse models of DMD and extremely scarce in the limb muscles of these mice. In vitro, the EOMCD34 cells had myogenic potential, forming myotubes in differentiation media. After determining a media better able to induce proliferation in these cells, a fusion index was calculated. The cells isolated from EOM had a 40% higher fusion index compared to the same cells isolated from limb muscle. The EOMCD34 cells were resistant to both oxidative stress and mechanical injury. These data support our hypothesis that the EOM may be spared in aging and in muscular dystrophies due to a

  15. Sparing of extraocular muscle in aging and muscular dystrophies: a myogenic precursor cell hypothesis.

    Science.gov (United States)

    Kallestad, Kristen M; Hebert, Sadie L; McDonald, Abby A; Daniel, Mark L; Cu, Sharon R; McLoon, Linda K

    2011-04-01

    The extraocular muscles (EOM) are spared from pathology in aging and many forms of muscular dystrophy. Despite many studies, this sparing remains an enigma. The EOM have a distinct embryonic lineage compared to somite-derived muscles, and we have shown that they continuously remodel throughout life, maintaining a population of activated satellite cells even in aging. These data suggested the hypothesis that there is a population of myogenic precursor cells (mpcs) in EOM that is different from those in limb, with either elevated numbers of stem cells and/or mpcs with superior proliferative capacity compared to mpcs in limb. Using flow cytometry, EOM and limb muscle mononuclear cells were compared, and a number of differences were seen. Using two different cell isolation methods, EOM have significantly more mpcs per mg muscle than limb skeletal muscle. One specific subpopulation significantly increased in EOM compared to limb was positive for CD34 and negative for Sca-1, M-cadherin, CD31, and CD45. We named these the EOMCD34 cells. Similar percentages of EOMCD34 cells were present in both newborn EOM and limb muscle. They were retained in aged EOM, whereas the population decreased significantly in adult limb muscle and were extremely scarce in aged limb muscle. Most importantly, the percentage of EOMCD34 cells was elevated in the EOM from both the mdx and the mdx/utrophin(-/-) (DKO) mouse models of DMD and extremely scarce in the limb muscles of these mice. In vitro, the EOMCD34 cells had myogenic potential, forming myotubes in differentiation media. After determining a media better able to induce proliferation in these cells, a fusion index was calculated. The cells isolated from EOM had a 40% higher fusion index compared to the same cells isolated from limb muscle. The EOMCD34 cells were resistant to both oxidative stress and mechanical injury. These data support our hypothesis that the EOM may be spared in aging and in muscular dystrophies due to a subpopulation

  16. Adipose-Derived Mesenchymal Stem Cells Restore Impaired Mucosal Immune Responses in Aged Mice.

    Directory of Open Access Journals (Sweden)

    Kazuyoshi Aso

    Full Text Available It has been shown that adipose-derived mesenchymal stem cells (AMSCs can differentiate into adipocytes, chondrocytes and osteoblasts. Several clinical trials have shown the ability of AMSCs to regenerate these differentiated cell types. Age-associated dysregulation of the gastrointestinal (GI immune system has been well documented. Our previous studies showed that impaired mucosal immunity in the GI tract occurs earlier during agingthan is seen in the systemic compartment. In this study, we examined the potential of AMSCs to restore the GI mucosal immune system in aged mice. Aged (>18 mo old mice were adoptively transferred with AMSCs. Two weeks later, mice were orally immunized with ovalbumin (OVA plus cholera toxin (CT three times at weekly intervals. Seven days after the final immunization, when fecal extract samples and plasma were subjected to OVA- and CT-B-specific ELISA, elevated levels of mucosal secretory IgA (SIgA and plasma IgG antibody (Ab responses were noted in aged mouse recipients. Similar results were also seen aged mice which received AMSCs at one year of age. When cytokine production was examined, OVA-stimulated Peyer's patch CD4+ T cells produced increased levels of IL-4. Further, CD4+ T cells from the lamina propria revealed elevated levels of IL-4 and IFN-γ production. In contrast, aged mice without AMSC transfer showed essentially no OVA- or CT-B-specific mucosal SIgA or plasma IgG Ab or cytokine responses. Of importance, fecal extracts from AMSC transferred aged mice showed neutralization activity to CT intoxication. These results suggest that AMSCs can restore impaired mucosal immunity in the GI tract of aged mice.

  17. The effects of proliferation and DNA damage on hematopoietic stem cell function determine aging.

    Science.gov (United States)

    Khurana, Satish

    2016-07-01

    In most of the mammalian tissues, homeostasis as well as injury repair depend upon a small number of resident adult stem cells. The decline in tissue/organ function in aged organisms has been directly linked with poorly functioning stem cells. Altered function of hematopoietic stem cells (HSCs) is at the center of an aging hematopoietic system, a tissue with high cellular turnover. Poorly engrafting, myeloid-biased HSCs with higher levels of DNA damage accumulation are the hallmark features of an aged hematopoietic system. These cells show a higher proliferation rate than their younger counterparts. It was proposed that quiescence of these cells over long period of time leads to accumulation of DNA damage, eventually resulting in poor function/pathological conditions in hematopoietic system. However, various mouse models with premature aging phenotype also show highly proliferative HSCs. This review examines the evidence that links proliferation of HSCs with aging, which leads to functional changes in the hematopoietic system. Developmental Dynamics 245:739-750, 2016. © 2016 Wiley Periodicals, Inc.

  18. Vegetation reconstruction of Bronze Age by using microscopic structure of charcoals

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The microscopic structure of charcoals was determined in two sites of Bronze Age, Chifeng area by using the scanning electronic microscope. The results showed that these charcoals are all timbers of Mongolian oak (Quercus mongolica). It has powerful climatic indicative significance. Based on the assemblage of pollen composition, their eco-climatic index and character of community, the vegetation reconstruction of Bronze Age was obtained. The reconstruction showed that the zonal vegetation was Mongolian oak forest and Chinese pine forest in the loess hills in the Chifeng area, which suggested that the climatic condition was warmer and wetter at that time than present time.

  19. Definitions of fitness in age-structured populations: Comparison in the haploid case.

    Science.gov (United States)

    Lessard, Sabin; Soares, Cintia

    2016-02-21

    Fisher's (1930) Fundamental Theorem of Natural Selection (FTNS), and in particular the development of an explicit age-structured version of the theorem, is of everlasting interest. In a recent paper, Grafen (2015a) argues that Fisher regarded his theorem as justifying individual rather than population fitness maximization. The argument relies on a new definition of fitness in age-structured populations in terms of individual birth and death rates and age-specific reproductive values in agreement with a principle of neutrality. The latter are frequency-dependent and defined without reference to genetic variation. In the same paper, it is shown that the rate of increase in the mean of the breeding values of fitness weighted by the reproductive values, but keeping the breeding values constant as in Price (1972) is equal to the additive genetic variance in fitness. Therefore, this partial change is obtained by keeping constant not only the genotypic birth and death rates but also the mean age-specific birth and death rates from which the age-specific reproductive values are defined. In this paper we reaffirm that the Malthusian parameter which measures the relative rate of increase or decrease in reproductive value of each genotype in a continuous-time age-structured population is the definition of fitness used in Fisher's (1930) FTNS. This is shown by considering an age-structured asexual haploid population with constant age-specific birth and death (or survival) parameters for each type. Although the original statement of the FTNS is for a diploid population, this simplified haploid model allows us to address the definition of fitness meant in this theorem without the complexities and effects of a changing genic environment. In this simplified framework, the rate of change in mean fitness in continuous time is expected to be exactly equal to the genetic variance in fitness (or to the genetic variance in fitness divided by the mean fitness in discrete time), which can

  20. Traveling wave dispersal in partially sedentary age-structured biological populations

    CERN Document Server

    Le, Thuc Manh; Van Minh, Nguyen

    2010-01-01

    In this paper we present a thorough study on the existence of traveling waves in a mathematical model of dispersal in a partially sedentary age-structured population. This type of model was first proposed by Veit and Lewis in [{\\it Am. Nat.}, {\\bf 148} (1996), 255-274]. We choose the fecundity function to be the Beverton-Holt type function. We extend the theory of traveling waves in the population genetics model of Weinberger in [{\\it SIAM J. Math. Anal.}, {\\bf 13} (1982), 353-396] to the case when migration depends on age groups and a fraction of the population does not migrate.

  1. Age and decision strategies in running memory for speech: effects of prosody and linguistic structure.

    Science.gov (United States)

    Wingfield, A; Lahar, C J; Stine, E A

    1989-07-01

    Young and elderly adults heard recorded passages of English prose spoken with and without normal prosody, and passages that were devoid of either linguistic or prosodic structure. Subjects were instructed to interrupt the speech input at points of their choosing for immediate recall on a segment-by-segment basis. For both age groups segmentation strategies varied with type of speech materials as did their levels of recall accuracy. Age differences in recall performance were diminished by the presence of normal prosody, an effect only partially attributable to the use of prosody to detect linguistic boundaries at the surface level.

  2. Aging population in change – a crucial challenge for structurally weak rural areas in Austria

    Directory of Open Access Journals (Sweden)

    Fischer Tatjana

    2014-03-01

    Full Text Available Besides population decline, structurally weak rural areas in Austria face a new challenge related to demographic change: the increasing heterogeneity of their aging population. From the example of the so-called ‘best agers’ - comprising people aged 55 to 65 years - this contribution makes visible patterns and consequences of growing individualized spatial behaviour and spatial perception. Furthermore, contradictions between claims, wishes and expectations and actual engagement and commitment to their residential rural municipalities are being pointed out. These empirically-based facts are rounded off by considerations on the best agers’ future migration-behaviour and the challenges for spatial planning at the municipal level.

  3. SIRT1 ameliorates age-related senescence of mesenchymal stem cells via modulating telomere shelterin

    Directory of Open Access Journals (Sweden)

    Huiqiang eChen

    2014-06-01

    Full Text Available Age-related mesenchymal stem cells (MSCs senescence, which impairs its tissue repair capacity in vivo and hence compromises the effects of MSCs-based therapy in clinical applications, is closely related to aging and aging-related diseases. Here, we demonstrated the effect of SIRT1, a NAD+-dependent deacetylase, on age-related MSCs senescence. Knockdown of SIRT1 in young MSCs induces cellular senescence and inhibits cellular proliferation ability whereas overexpression of SIRT1 in aged MSCs reversed the cellular senescence and regained its proliferation capacity, suggesting that SIRT1 could modulate age-induced MSCs senescence. Aging-related proteins, P16 and P21, might be involved in SIRT1-mediated anti-aging effect on MSCs. SIRT1 could positively modulate age-related DNA damage in MSCs. In addition, SIRT1 could induce telomerase reverse transcriptase (TERT expression and consequently enhance telomerase activity, however, no significant change was observed in telomere length. Moreover, SIRT1 could positively regulate TPP1, an important member of telomere shelterin, expression. Together, these results demonstrate that SIRT1 dampens age-related MSCs senescence, which was correlated with the up-regulation of TPP1 expression, telomerase activity and down-regulation of DNA damage.

  4. In-cell infection: a novel pathway for Epstein-Barr virus infection mediated by cell-in-cell structures.

    Science.gov (United States)

    Ni, Chao; Chen, Yuhui; Zeng, Musheng; Pei, Rongjuan; Du, Yong; Tang, Linquan; Wang, Mengyi; Hu, Yazhuo; Zhu, Hanyu; He, Meifang; Wei, Xiawei; Wang, Shan; Ning, Xiangkai; Wang, Manna; Wang, Jufang; Ma, Li; Chen, Xinwen; Sun, Qiang; Tang, Hong; Wang, Ying; Wang, Xiaoning

    2015-07-01

    Epstein-Barr virus (EBV) can infect both susceptible B lymphocytes and non-susceptible epithelial cells (ECs). Viral tropism analyses have revealed two intriguing means of EBV infection, either by a receptor-mediated infection of B cells or by a cell-to-cell contact-mediated infection of non-susceptible ECs. Herein, we report a novel "in-cell infection" mechanism for EBV infection of non-susceptible ECs through the formation of cell-in-cell structures. Epithelial CNE-2 cells were invaded by EBV-infected Akata B cells to form cell-in-cell structures in vitro. Such unique cellular structures could be readily observed in the specimens of nasopharyngeal carcinoma. Importantly, the formation of cell-in-cell structures led to the autonomous activation of EBV within Akata cells and subsequent viral transmission to CNE-2 cells, as evidenced by the expression of viral genes and the presence of virion particles in CNE-2 cells. Significantly, EBV generated from in-cell infected ECs displayed altered tropism with higher infection efficacy to both B cells and ECs. In addition to CNE-2 tumor cells, cell-in-cell structure formation could also mediate EBV infection of NPEC1-Bmi1 cells, an immortalized nasopharyngeal epithelial cell line. Furthermore, efficient infection by this mechanism involved the activation of the PI3K/AKT signaling pathway. Thus, our study identified "in-cell infection" as a novel mechanism for EBV infection. Given the diversity of virus-infected cells and the prevalence of cell-in-cell structures during chronic infection, we speculate that "in-cell infection" is likely a general mechanism for EBV and other viruses to infect non-susceptible ECs.

  5. Aged nano-structured platinum based catalyst: effect of chemical treatment on adsorption and catalytic activity.

    Science.gov (United States)

    Shim, Wang Geun; Nahm, Seung Won; Park, Hyuk Ryeol; Yun, Hyung Sun; Seo, Seong Gyu; Kim, Sang Chai

    2011-02-01

    To examine the effect of chemical treatment on the adsorption and catalytic activity of nanostructured platinum based catalyst, the aged commercial Pt/AC catalyst was pretreated with sulfuric acid (H2SO4) and a cleaning agent (Hexane). Several reliable methods such as nitrogen adsorption, X-ray powder diffraction (XRD), scanning electron microscopy (SEM) and inductively coupled plasma (ICP) were employed to characterize the aged Pt/AC catalyst and its chemically pretreated Pt/AC catalysts. The catalytic and adsorption activities of nano-structured heterogeneous Pt/AC catalyst were investigated on the basis of toluene oxidation and adsorption isotherm data. In addition, the adsorption isotherms of toluene were used to calculate the adsorption energy distribution functions for the parent catalyst and its pre-treated nano-structured Pt/AC catalysts. It was found that sulfuric acid aqueous treatment can enhance the catalytic performance of aged Pt/AC catalyst toward catalytic oxidation of toluene. It was also shown that a comparative analysis of the energy distribution functions for nano-structured Pt/AC catalysts as well as the pore size distribution provides valuable information about their structural and energetic heterogeneity.

  6. Cilia containing 9 + 2 structures grown from immortalized cells

    Institute of Scientific and Technical Information of China (English)

    Ming Zhang; Jose G Assouline

    2007-01-01

    Cilia depend on their highly differentiated structure, a 9 + 2 arrangement, to remove particles from the lung and to transport reproductive cells. Immortalized cells could potentially be of great use in cilia research. Immortalization of cells with cilia structure containing the 9 + 2 arrangement might be able to generate cell lines with such cilia structure. However, whether immortalized cells can retain such a highly differentiated structure remains unclear. Here we demonstrate that (1) using E1a gene transfection, tracheal cells are immortalized; (2) interestingly, in a gel culture the immortalized cells form spherical aggregations within which a lumen is developed; and (3) surprisingly, inside the aggregation, cilia containing a 9 + 2 arrangement grow from the cell's apical pole and protrude into the lumen. These results may influence future research in many areas such as understanding the mechanisms of cilia differentiation, cilia generation in other existing cell lines, cilia disorders, generation of other highly differentiated structures besides cilia using the gel culture,immortalization of other ciliated cells with the E1a gene, development of cilia motile function, and establishment of a research model to provide uniform ciliated cells.

  7. GH mediates exercise-dependent activation of SVZ neural precursor cells in aged mice.

    Directory of Open Access Journals (Sweden)

    Daniel G Blackmore

    Full Text Available Here we demonstrate, both in vivo and in vitro, that growth hormone (GH mediates precursor cell activation in the subventricular zone (SVZ of the aged (12-month-old brain following exercise, and that GH signaling stimulates precursor activation to a similar extent to exercise. Our results reveal that both addition of GH in culture and direct intracerebroventricular infusion of GH stimulate neural precursor cells in the aged brain. In contrast, no increase in neurosphere numbers was observed in GH receptor null animals following exercise. Continuous infusion of a GH antagonist into the lateral ventricle of wild-type animals completely abolished the exercise-induced increase in neural precursor cell number. Given that the aged brain does not recover well after injury, we investigated the direct effect of exercise and GH on neural precursor cell activation following irradiation. This revealed that physical exercise as well as infusion of GH promoted repopulation of neural precursor cells in irradiated aged animals. Conversely, infusion of a GH antagonist during exercise prevented recovery of precursor cells in the SVZ following irradiation.

  8. Aging of the rat adrenocortical cell: response to ACTH and cyclic AMP in vitro.

    Science.gov (United States)

    Malamed, S; Carsia, R V

    1983-03-01

    To study intrinsic age-related changes in adrenocortical steroid production, cells isolated from rats of different ages (3 to 24 months) were used. Acute (2 hour) corticosterone production in response to stimulation by adrenocorticotrophic hormone (ACTH) and adenosine 3':5'-cyclic monophosphate (cAMP) was measured by radioimmunoassay. With age, adrenocortical cells lose much of their ability to produce corticosterone in the absence or presence of ACTH or cAMP. The loss is progressive from 6 to 24 months of age. Analysis of the data suggests that from 6 to 12 months, an intracellular steroidogenic lesion develops; in addition there may be a loss in ACTH receptors on the plasma membrane. After 12 months these defects increase and are accompanied by a decrease in receptor sensitivity to ACTH.

  9. Human T cell aging and the impact of persistent viral infections

    Directory of Open Access Journals (Sweden)

    Tamas eFulop

    2013-09-01

    Full Text Available Aging is associated with a dysregulation of the immune response, loosely termed immunosenescence. Each part of the immune system is influenced to some extent by the aging process. However, adaptive immunity seems more extensively affected and among all participating cells it is the T cells that are most altered. There is a large body of experimental work devoted to the investigation of age-associated differences in T cell phenotypes and functions in young and old individuals, but few longitudinal studies in humans actually delineating changes at the level of the individual. In most studies, the number and proportion of late-differentiated T cells, especially CD8+ T cells, is reported to be higher in the elderly than in the young. Limited longitudinal studies suggest that accumulation of these cells is a dynamic process and does indeed represent an age-associated change. Accumulations of such late-stage cells may contribute to the enhanced systemic pro-inflammatory milieu commonly seen in older people. We do not know exactly what causes these observed changes, but an understanding of the possible causes is now beginning to emerge. A favored hypothesis is that these events are at least partly due to the effects of the maintenance of essential immune surveillance against persistent viral infections, notably Cytomegalovirus (CMV, which may exhaust the immune system over time. It is still a matter of debate as to whether these changes are compensatory and beneficial or pathological and detrimental to the proper functioning of the immune system and whether they impact longevity. Here, we will review present knowledge of T cell changes with aging and their relation to chronic viral and possibly other persistent infections.

  10. Age related differences in dynamics of specific memory B cell populations after clinical pertussis infection.

    Directory of Open Access Journals (Sweden)

    Inonge van Twillert

    Full Text Available For a better understanding of the maintenance of immune mechanisms to Bordetella pertussis (Bp in relation to age, we investigated the dynamic range of specific B cell responses in various age-groups at different time points after a laboratory confirmed pertussis infection. Blood samples were obtained in a Dutch cross sectional observational study from symptomatic pertussis cases. Lymphocyte subpopulations were phenotyped by flowcytometry before and after culture. Memory B (Bmem cells were differentiated into IgG antibody secreting cells (ASC by polyclonal stimulation and detected by an ELISPOT assay specific for pertussis antigens pertussis toxin (Ptx, filamentous haemagglutinin (FHA and pertactin (Prn. Bp antigen specific IgG concentrations in plasma were determined using multiplex technology. The majority of subjects having experienced a clinical pertussis episode demonstrated high levels of both Bp specific IgG and Bmem cell levels within the first 6 weeks after diagnosis. Significantly lower levels were observed thereafter. Waning of cellular and humoral immunity to maintenance levels occurred within 9 months after antigen encounter. Age was found to determine the maximum but not base-line frequencies of Bmem cell populations; higher levels of Bmem cells specific for Ptx and FHA were reached in adults and (pre- elderly compared to under-fours and schoolchildren in the first 6 weeks after Bp exposure, whereas not in later phases. This age effect was less obvious for specific IgG levels. Nonetheless, subjects' levels of specific Bmem cells and specific IgG were weakly correlated. This is the first study to show that both age and closeness to last Bp encounter impacts the size of Bp specific Bmem cell and plasma IgG levels.

  11. Metformin inhibits advanced glycation end products (AGEs)-induced renal tubular cell injury by suppressing reactive oxygen species generation via reducing receptor for AGEs (RAGE) expression.

    Science.gov (United States)

    Ishibashi, Y; Matsui, T; Takeuchi, M; Yamagishi, S

    2012-11-01

    Advanced glycation end products (AGEs) and their receptor (RAGE) play a role in tubulointerstitial damage in diabetic nephropathy. Recently, metformin has been shown to ameliorate tubular injury both in cell culture and diabetic animal model. However, effects of metformin on AGEs-induced tubular cell apoptosis and damage remain unknown. We examined here whether and how metformin could block the AGEs-RAGE-elicited tubular cell injury in vitro. Gene expression level was evaluated by real-time reverse-transcription polymerase chain reactions. Reactive oxygen species (ROS) generation was measured with dihydroethidium staining. Apoptosis was evaluated by DNA fragmentation and annexin V expression level. AGEs upregulated RAGE mRNA levels and subsequently increased ROS generation and intercellular adhesion molecule-1, monocyte chemoattractant protein-1 and transforming growth factor-β gene expression in human renal proximal tubular cells, all of which were significantly blocked by the treatment of 0.01 and 0.1 mM metformin. Compound C, an inhibitor of AMP-activated protein kinase significantly blocked the effects of metformin on RAGE gene expression and ROS generation in AGEs-exposed tubular cells. Furthermore, metformin dose-dependently inhibited the AGEs-induced apoptotic cell death of tubular cells; 1 mM metformin completely suppressed the pro-apoptotic effects of AGEs in 2 different assay systems. Our present study suggests that metformin could inhibit the AGEs-induced apoptosis and inflammatory and fibrotic reactions in tubular cells probably by reducing ROS generation via suppression of RAGE expression through AMP-activated protein kinase activation. Metformin may protect against tubular cell injury in diabetic nephropathy by blocking the AGEs-RAGE-ROS axis.

  12. Growth hormone-releasing peptide-6 inhibits cerebellar cell death in aged rats.

    Science.gov (United States)

    Pañeda, Covadonga; Arroba, Ana I; Frago, Laura M; Holm, Anne Mette; Rømer, John; Argente, Jesús; Chowen, Julie A

    2003-08-26

    Insulin-like growth factor (IGF)-I is essential for cerebellar granule neuron survival and a decline in IGF-I is implicated in various age-dependent processes. Here we show that IGF-I mRNA levels are decreased in the cerebellum of old rats compared with young rats and this was associated with increased cell death and activation of caspases 3 and 9. Growth hormone-releasing peptide (GHRP)-6, a synthetic ligand for the ghrelin receptor, increased IGF-I mRNA levels, decreased cell death and inhibited caspase 3 and 9 activation in the cerebellum of aged rats. These results suggest that increasing IGF-I expression in the cerebellum can decrease cell death in aged rats via inhibition of caspase 3 and 9 activation.

  13. Production of interferon-γ by natural killer cells and aging in chronic human schistosomiasis

    Directory of Open Access Journals (Sweden)

    E. Speziali

    2004-01-01

    Full Text Available BACKGROUNG: Aging is associated with several alterations in the phenotype, repertoire and activation status of lymphocytes as well as in the cytokine profile produced by these cells. As a lifelong condition, chronic parasitic diseases such as human schistosomiasis overlaps with the aging process and no systematic study has yet addressed the changes in immune response during infection with Schistosoma mansoni in older individuals.

  14. AMPK Functions to Modulate Tissue and Organismal Aging in a Cell Non-Autonomous Manner

    OpenAIRE

    Ulgherait, Matthew John

    2014-01-01

    Understanding the biological mechanisms of aging represents an urgent biomedical challenge. AMP-activated protein kinase (AMPK) exhibits pro-longevity effects in diverse species. However, the tissue-specific mechanisms involved in AMPK regulation of aging are poorly understood. Here, we show that activation of AMPK in the adult Drosophila nervous system induces autophagy both in the brain and the intestinal epithelium. These cell autonomous and non-autonomous functions of AMPK are linked ...

  15. Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug.

    Science.gov (United States)

    Marschallinger, Julia; Schäffner, Iris; Klein, Barbara; Gelfert, Renate; Rivera, Francisco J; Illes, Sebastian; Grassner, Lukas; Janssen, Maximilian; Rotheneichner, Peter; Schmuckermair, Claudia; Coras, Roland; Boccazzi, Marta; Chishty, Mansoor; Lagler, Florian B; Renic, Marija; Bauer, Hans-Christian; Singewald, Nicolas; Blümcke, Ingmar; Bogdahn, Ulrich; Couillard-Despres, Sebastien; Lie, D Chichung; Abbracchio, Maria P; Aigner, Ludwig

    2015-10-27

    As human life expectancy has improved rapidly in industrialized societies, age-related cognitive impairment presents an increasing challenge. Targeting histopathological processes that correlate with age-related cognitive declines, such as neuroinflammation, low levels of neurogenesis, disrupted blood-brain barrier and altered neuronal activity, might lead to structural and functional rejuvenation of the aged brain. Here we show that a 6-week treatment of young (4 months) and old (20 months) rats with montelukast, a marketed anti-asthmatic drug antagonizing leukotriene receptors, reduces neuroinflammation, elevates hippocampal neurogenesis and improves learning and memory in old animals. By using gene knockdown and knockout approaches, we demonstrate that the effect is mediated through inhibition of the GPR17 receptor. This work illustrates that inhibition of leukotriene receptor signalling might represent a safe and druggable target to restore cognitive functions in old individuals and paves the way for future clinical translation of leukotriene receptor inhibition for the treatment of dementias.

  16. Naturally occurring and stress induced tubular structures from mammalian cells, a survival mechanism

    Directory of Open Access Journals (Sweden)

    He Jian

    2007-08-01

    Full Text Available Abstract Background Tubular shaped mammalian cells in response to dehydration have not been previously reported. This may be due to the invisibility of these cells in aqueous solution, and because sugars and salts added to the cell culture for manipulation of the osmotic conditions inhibit transformation of normal cells into tubular shaped structures. Results We report the transformation of normal spherical mammalian cells into tubular shaped structures in response to stress. We have termed these transformed structures 'straw cells' which we have associated with a variety of human tissue types, including fresh, post mortem and frozen lung, liver, skin, and heart. We have also documented the presence of straw cells in bovine brain and prostate tissues of mice. The number of straw cells in heart, lung tissues, and collapsed straw cells in urine increases with the age of the mammal. Straw cells were also reproduced in vitro from human cancer cells (THP1, CACO2, and MCF7 and mouse stem cells (D1 and adipose D1 by dehydrating cultured cells. The tubular center of the straw cells is much smaller than the original cell; houses condensed organelles and have filamentous extensions that are covered with microscopic hair-like structures and circular openings. When rehydrated, the filaments uptake water rapidly. The straw cell walls, have a range of 120 nm to 200 nm and are composed of sulfated-glucose polymers and glycosylated acidic proteins. The transformation from normal cell to straw cells takes 5 to 8 hr in open-air. This process is characterized by an increase in metabolic activity. When rehydrated, the straw cells regain their normal spherical shape and begin to divide in 10 to 15 days. Like various types of microbial spores, straw cells are resistant to harsh environmental conditions such as UV-C radiation. Conclusion Straw cells are specialized cellular structures and not artifacts from spontaneous polymerization, which are generated in response

  17. Structural basis of cell-cell adhesion by NCAM

    DEFF Research Database (Denmark)

    Kasper, C; Rasmussen, H; Kastrup, Jette Sandholm Jensen;

    2000-01-01

    and learning. The 1.85 A crystal structure of the two N-terminal extracellular domains of NCAM reported here provides a structural basis for the homophilic interaction. The molecular packing of the two-domain structure reveals a cross shaped antiparallel dimer, and provides fundamental insight into trans...

  18. Postnatal development, maturation and aging in the mouse cochlea and their effects on hair cell regeneration.

    Science.gov (United States)

    Walters, Bradley J; Zuo, Jian

    2013-03-01

    The organ of Corti in the mammalian inner ear is comprised of mechanosensory hair cells (HCs) and nonsensory supporting cells (SCs), both of which are believed to be terminally post-mitotic beyond late embryonic ages. Consequently, regeneration of HCs and SCs does not occur naturally in the adult mammalian cochlea, though recent evidence suggests that these cells may not be completely or irreversibly quiescent at earlier postnatal ages. Furthermore, regenerative processes can be induced by genetic and pharmacological manipulations, but, more and more reports suggest that regenerative potential declines as the organ of Corti continues to age. In numerous mammalian systems, such effects of aging on regenerative potential are well established. However, in the cochlea, the problem of regeneration has not been traditionally viewed as one of aging. This is an important consideration as current models are unable to elicit widespread regeneration or full recovery of function at adult ages yet regenerative therapies will need to be developed specifically for adult populations. Still, the advent of gene targeting and other genetic manipulations has established mice as critically important models for the study of cochlear development and HC regeneration and suggests that auditory HC regeneration in adult mammals may indeed be possible. Thus, this review will focus on the pursuit of regeneration in the postnatal and adult mouse cochlea and highlight processes that occur during postnatal development, maturation, and aging that could contribute to an age-related decline in regenerative potential. Second, we will draw upon the wealth of knowledge pertaining to age related senescence in tissues outside of the ear to synthesize new insights and potentially guide future research aimed at promoting HC regeneration in the adult cochlea.

  19. [Is it possible to "cancel" aging process of cell cultures under optimal conditions for cultivation?].

    Science.gov (United States)

    Bozhkov, A I; Kovaleva, M K; Menzianova, N G

    2011-01-01

    The characteristics of the cells epigenotypes Dunaliella viridis Teod. in the process of chronological and replicative aging were investigated. By 40th day of accumulative cultivation (which coincided with the stationary growth phase) DNA content in the cells of Dunaliella viridis increased 2 times, triacylglycerides 3 times, beta-carotene and carbonyl proteins 2 times, RNA content decreased in comparison with cells in exponential growth phase, i. e., the 40th day of growth of culture forms the age-related epigenotype. 4 received subcultures were being transplanted during 2 years in mid-logarithmic growth phase (subculture-10), early stationary phase of growth (subculture-20), in the mid-stationary growth phase (subculture-30), and late stationary growth phase (subculture-40). It is shown that epigenotype of subculture-10 remained unchanged over 2 years of cultivation, i. e., it does not manifest replicative aging. At the same time, the subculture-20, although long enough (at least 40 passages), maintained epigenotype characteristic of young cultures, and showed age-related changes. Pronounced age-dependent changes of epigenotype in the course of cultivation were identified for subculture-30, and subculture-40 was characterized by unstable epigenotype. Thus, cultivation conditions determine the intensity of replicative aging in Dunaliella viridis.

  20. Effects of aging on mouse tongue epithelium focusing on cell proliferation rate and morphological aspects.

    Science.gov (United States)

    Carrard, Vinicius Coelho; Pires, Aline Segatto; Badauy, Cristiano Macabu; Rados, Pantelis Varvaki; Lauxen, Isabel Silva; Sant'Ana Filho, Manoel

    2008-11-01

    The aim of this study was to investigate cell proliferation rate and certain morphological features of mouse epithelium as aging progresses. Tongue biopsies were performed on female mice (Mus domesticus domesticus) at 2, 8, 14 and 20 months of age as indicative of adolescence, adulthood, early senescence and senescence, respectively. Histological sections of tongue were stained with hematoxylin-eosin and subjected to silver staining for active nucleolar organizer region counting. Cell proliferation rate and epithelial thickness analysis were carried out. Analysis of variance detected no differences between the groups in terms of numbers of silver-stained dots associated with nucleolar proteins. There was an increase in mean epithelial thickness in adult animals, followed by a gradual reduction until senescence. Mean keratin thickness presented an increase at 8 and 20 months of age. This difference is probably related to puberty, growth or dietary habits. Aging has no influence on oral epithelial proliferation rate in mice. A gradual reduction in epithelial thickness is a feature of aging in mammals. A conspicuous increase in the keratin layer was observed in senescence as an adaptative response to the reduction in epithelial thickness. These results suggest that aging affects the oral epithelium maturation process through a mechanism that is not related to cell proliferation.

  1. Down-regulation of LAK cell-mediated cytotoxicity: cancer and ageing.

    Science.gov (United States)

    Bykovskaya, S N; Abronina, I F; Kupriyanova, T A; Bubenik, J

    1990-01-01

    A comparative study was made of the generation of lymphokine-activated killer (LAK) cells in patients with melanoma and healthy donors of different age groups. Significant reduction of effector cell cytotoxicity in patients following 72 h culture with 1,000 U/ml or recombinant IL-2 (rIL-2) as well as a decreased ability to generate LAK cells in elderly individuals were shown to be correlated with suppressor cell activation in rIL-2 stimulated cell population. Suppressor effect depends on monocytes and T-lymphocytes: partial abolition of suppression in LAK cells was observed following removal of adherent cells or treatment with OKT8 monoclonal antibodies and complement.

  2. DETERMINING THE EFFECTS OF RADIATION ON AGING CONCRETE STRUCTURES OF NUCLEAR REACTORS

    Energy Technology Data Exchange (ETDEWEB)

    Serrato, M.

    2010-01-29

    The U.S. Department of Energy Office of Environmental Management (DOE-EM) is responsible for the Decontamination and Decommissioning (D&D) of nuclear facilities throughout the DOE Complex. Some of these facilities will be completely dismantled, while others will be partially dismantled and the remaining structure will be stabilized with cementitious fill materials. The latter is a process known as In-Situ Decommissioning (ISD). The ISD decision process requires a detailed understanding of the existing facility conditions, and operational history. System information and material properties are need for aged nuclear facilities. This literature review investigated the properties of aged concrete structures affected by radiation. In particular, this review addresses the Savannah River Site (SRS) isotope production nuclear reactors. The concrete in the reactors at SRS was not seriously damaged by the levels of radiation exposure. Loss of composite compressive strength was the most common effect of radiation induced damage documented at nuclear power plants.

  3. A stochastic step model of replicative senescence explains ROS production rate in ageing cell populations.

    Directory of Open Access Journals (Sweden)

    Conor Lawless

    Full Text Available Increases in cellular Reactive Oxygen Species (ROS concentration with age have been observed repeatedly in mammalian tissues. Concomitant increases in the proportion of replicatively senescent cells in ageing mammalian tissues have also been observed. Populations of mitotic human fibroblasts cultured in vitro, undergoing transition from proliferation competence to replicative senescence are useful models of ageing human tissues. Similar exponential increases in ROS with age have been observed in this model system. Tracking individual cells in dividing populations is difficult, and so the vast majority of observations have been cross-sectional, at the population level, rather than longitudinal observations of individual cells.One possible explanation for these observations is an exponential increase in ROS in individual fibroblasts with time (e.g. resulting from a vicious cycle between cellular ROS and damage. However, we demonstrate an alternative, simple hypothesis, equally consistent with these observations which does not depend on any gradual increase in ROS concentration: the Stochastic Step Model of Replicative Senescence (SSMRS. We also demonstrate that, consistent with the SSMRS, neither proliferation-competent human fibroblasts of any age, nor populations of hTERT overexpressing human fibroblasts passaged beyond the Hayflick limit, display high ROS concentrations. We conclude that longitudinal studies of single cells and their lineages are now required for testing hypotheses about roles and mechanisms of ROS increase during replicative senescence.

  4. Scientific paradigms of structural safety of aged plants-Lessons learned from Russian activities

    Energy Technology Data Exchange (ETDEWEB)

    Saji, Genn [Ex-Secretariat of Nuclear Safety Commission (Japan)], E-mail: sajig@bd5.so-net.ne.jp; Timofeev, Boris [CRISM Prometey, Shpalernaja 49, St. Petersburg 193015 (Russian Federation)

    2009-09-15

    The study of the effects behind the degradation of components and materials is becoming increasingly important for the safe operation of aged plants especially when it comes to life extension. Since the Russian nuclear community began to examine life extension issues nearly 15 years ago, there is much to learn from these pioneering studies. At the Ninth International Conference entitled 'Material Issues in Design, Manufacturing and Operation of Nuclear Power Plants Equipment' held in St. Petersburg, 2006, recent data were introduced regarding the ageing effects of mechanical properties of various kinds of steel and welding joints of Russian NPP components. The meeting was organized by the Central Research Institute of Structural Materials (CRISM) 'Prometey' in cooperation with the IAEA and JRC-EU. In reviewing the recent data presented at the Ninth Conference, the authors believe that the paradigms of structural integrity issues in aged plants are now reasonably well established in (1) fracture mechanics and irradiation hardening of reactor vessels and core internals and (2) thermal ageing and annealing effects. However, the first author, G. Saji, believes that the current approach of low-cycle fatigue is still unable to prevent and predict environmentally assisted cracks such as demonstrated in the IGSCC issues in the down-comer pipes of RBMK plants and various steam generator corrosion issues. This fundamental flaw stems from design codes, which do not incorporate the basic knowledge of electrochemical corrosion mechanisms as represented by the corrosion current.

  5. Association between age and repair of oxidatively damaged DNA in human peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Løhr, Mille; Jensen, Annie; Eriksen, Louise;

    2015-01-01

    damaged DNA in peripheral blood mononuclear cells (PBMCs). We isolated PBMCs from subjects aged 18-83 years, as part of a health survey of the Danish population that focussed on lifestyle factors. The level of DNA repair activity was measured as incisions on potassium bromate-damaged DNA by the comet...... assay. There was an inverse association between age and DNA repair activity with a 0.65% decline in activity per year from age 18 to 83 (95% confidence interval: 0.16-1.14% per year). Univariate regression analysis also indicated inverse associations between DNA repair activity and waist-hip ratio (P...

  6. The association between Neovascular Age-related Macular Degeneration and Regulatory T cells in peripheral blood

    DEFF Research Database (Denmark)

    Madelung, Christopher Fugl; Falk, Mads; Sørensen, Torben Lykke

    2015-01-01

    PURPOSE: To investigate regulatory T cells (Tregs) and subsets of the Treg population in patients with neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: Twenty-one neovascular AMD cases and 12 age-matched controls without retinal pathology were selected. Patients were recr...... were found in the percentages of CD4(+) lymphocytes, CD25(high)CD127(low) Tregs, CD45RA(+) naïve Tregs, or CD31(+) recent thymic emigrant Tregs. CONCLUSION: Our data does not indicate an altered state of systemic Treg cells in neovascular AMD....

  7. Structural and functional findings in exudative age-related long-term macular degeneration

    OpenAIRE

    Riusala, Aila

    2013-01-01

    Age-related macular degeneration (AMD) is the leading cause of visual disability. During past years, new treatments have been studied frequently. However, only some studies have examined its long-term natural outcome. In the future, these kinds of studies are no longer possible because all the AMD lesions are treated. The purpose of this project was to investigate the end-stage structural and functional components of wet AMD and their connection to the fresh exudative lesion stage. The s...

  8. Traveling waves and spreading speed on a lattice model with age structure

    Directory of Open Access Journals (Sweden)

    Zongyi Wang

    2012-09-01

    Full Text Available In this article, we study a lattice differential model for a single species with distributed age-structure in an infinite patchy environment. Using method of approaches by Diekmann and Thieme, we develop a comparison principle and construct a suitable sub-solution to the given model, and show that there exists a spreading speed of the system which in fact coincides with the minimal wave speed.

  9. Seismically-induced structures in the Quaternary sediments of the NE Fennoscandian Shield: Features and age

    OpenAIRE

    Nikolaeva S. B.

    2016-01-01

    Results of studying secondary seismogenic deformations of the vibrational type (termed "seismites") in loose sediments of the north-eastern Baltic Shield (the Kola region) have been provided. The features, types, formation patterns and age of seismites have been considered. On the basis of previous results the major periods of the region activation in the Holocene have been defined. Criteria of identifying similar structures with widely spread glaciodislocations have been suggested. Results o...

  10. A multi-region nonlinear age-size structured fish population model

    CERN Document Server

    Faugeras, Blaise

    2010-01-01

    The goal of this paper is to present a generic multi-region nonlinear age-size structured fish population model, and to assess its mathematical well-posedness. An initial-boundary-value problem is formulated. Existence and uniqueness of a positive weak solution is proved. Eventually, a comparison result is derived: the population of all regions decreases as the mortality rate increases in at least one region.

  11. Cord blood versus age 5 mononuclear cell proliferation on IgE and asthma

    Directory of Open Access Journals (Sweden)

    Perera Frederica

    2010-08-01

    Full Text Available Abstract Background Fetal immune responses following exposure of mothers to allergens during pregnancy may influence the subsequent risk of childhood asthma. However, the association of allergen-induced cord blood mononuclear cell (CBMC proliferation and cytokine production with later allergic immune responses and asthma has been controversial. Our objective was to compare indoor allergen-induced CBMC with age 5 peripheral blood mononuclear cell (PBMC proliferation and determine which may be associated with age 5 allergic immune responses and asthma in an inner city cohort. Methods As part of an ongoing cohort study of the Columbia Center for Children's Environmental Health (CCCEH, CBMCs and age 5 PBMCs were cultured with cockroach, mouse, and dust mite protein extracts. CBMC proliferation and cytokine (IL-5 and IFN-γ responses, and age 5 PBMC proliferation responses, were compared to anti-cockroach, anti-mouse, and anti-dust mite IgE levels, wheeze, cough, eczema and asthma. Results Correlations between CBMC and age 5 PBMC proliferation in response to cockroach, mouse, and dust mite antigens were nonsignificant. Cockroach-, mouse-, and dust mite-induced CBMC proliferation and cytokine responses were not associated with allergen-specific IgE at ages 2, 3, and 5, or with asthma and eczema at age 5. However, after adjusting for potential confounders, age 5 cockroach-induced PBMC proliferation was associated with anti-cockroach IgE, total IgE, and asthma (p Conclusion In contrast to allergen-induced CBMC proliferation, age 5 cockroach-induced PBMC proliferation was associated with age 5 specific and total IgE, and asthma, in an inner-city cohort where cockroach allergens are prevalent and exposure can be high.

  12. Age-associated changes in microRNA expression in bone marrow derived dendritic cells.

    Science.gov (United States)

    Park, Seungbum; Kang, Soowon; Min, Kyung Hoon; Woo Hwang, Kwang; Min, Hyeyoung

    2013-01-01

    MiRNAs have shown to regulate aging process at the level of cellular senescence, tissue aging, and lifespan of whole organism. Given that many miRNAs also function as important regulators of hematopoietic system as well as aging process, it is highly likely that miRNAs would be involved in the changes of myeloid function and differentiation during aging. Therefore, here we examine differential expression of miRNAs in aged myeloid lineage cells and assess if altered miRNA expression pattern would reflect the change of miRNA targets and related function. We demonstrated that the expressions of myelogenic miRNAs such as miR-155, miR-223, miR-146a, miR-146b, miR-132, miR-142-5p, and miR-142-3p were increased in aged bone marrow derived dendritic cells (BMDC) under normal and activated conditions. We also observed that the expressions of IRAK1 and TRAF6, the targets of miR-146a, and DC-SIGN, a target of miR-155 were diminished while miR-146a and miR-155 were augmented during aging. In addition, we found that the production of pro-inflammatory cytokines, which is mediated by the activation of NF-kB pathway via IRAK1 and TRAF6, was greatly reduced in aged BMDC. Taken together, our data reveal that age-associated changes occur in miRNA expression in BMDC, and this altered miRNA expression affects miRNA target expression and compromises BMDC function such as cytokine production during aging.

  13. Structural equation modeling identifies markers of damage and function in the aging male Fischer 344 rat.

    Science.gov (United States)

    Grunz-Borgmann, Elizabeth A; Nichols, LaNita A; Wiedmeyer, Charles E; Spagnoli, Sean; Trzeciakowski, Jerome P; Parrish, Alan R

    2016-06-01

    The male Fischer 344 rat is an established model to study progressive renal dysfunction that is similar, but not identical, to chronic kidney disease (CKD) in humans. These studies were designed to assess age-dependent alterations in renal structure and function at late-life timepoints, 16-24 months. Elevations in BUN and plasma creatinine were not significant until 24 months, however, elevations in the more sensitive markers of function, plasma cystatin C and proteinuria, were detectable at 16 and 18 months, respectively. Interestingly, cystatin C levels were not corrected by caloric restriction. Urinary Kim-1, a marker of CKD, was elevated as early as 16 months. Klotho gene expression was significantly decreased at 24 months, but not at earlier timepoints. Alterations in renal structure, glomerulosclerosis and tubulointerstitial fibrosis, were noted at 16 months, with little change from 18 to 24 months. Tubulointerstitial inflammation was increased at 16 months, and remained similar from 18 to 24 months. A SEM (structural equation modeling) model of age-related renal dysfunction suggests that proteinuria is a marker of renal damage, while urinary Kim-1 is a marker of both damage and function. Taken together, these results demonstrate that age-dependent nephropathy begins as early as 16 months and progresses rapidly over the next 8 months.

  14. Dissecting simulated disk galaxies I: the structure of mono-age populations

    CERN Document Server

    Martig, Marie; Flynn, Chris

    2014-01-01

    We study seven simulated disk galaxies, three with a quiescent merger history, and four with mergers in their last 9 Gyr of evolution. We compare their structure at z=0 by decomposing them into "mono-age populations" (MAPs) of stars within 500 Myr age bins. All studied galaxies undergo a phase of merging activity at high redshift, so that stars older than 9 Gyr are found in a centrally concentrated component, while younger stars are mostly found in disks. We find that most MAPs have simple exponential radial and vertical density profiles, with a scale-height that typically increases with age. Because a large range of merger histories can create populations with simple structures, this suggests that the simplicity of the structure of mono-abundance populations observed in the Milky Way by Bovy et al. (2012b,c) is not necessarily a direct indicator of a quiescent history for the Milky Way. Similarly, the anti-correlation between scale-length and scale-height does not necessarily imply a merger-free history. How...

  15. Age-related brain trajectories in schizophrenia: a systematic review of structural MRI studies.

    Science.gov (United States)

    Chiapponi, Chiara; Piras, Fabrizio; Fagioli, Sabrina; Piras, Federica; Caltagirone, Carlo; Spalletta, Gianfranco

    2013-11-30

    Using the Pubmed database, we performed a detailed literature search for structural magnetic resonance imaging studies on patients with schizophrenia, investigating the relationship between macroscopic and microscopic structural parameters and age, to delineate an age-related trajectory. Twenty-six studies were considered for the review, from January 2000 to June 2012. Research results are heterogeneous because of the multifactorial features of schizophrenia and the multiplicity of the methodological approaches adopted. Some areas, within the amygdala-hippocampus complex, which are affected early in life by schizophrenia, age in a physiological way. Other regions, such as the superior temporal gyrus, appear already impaired at the onset of symptoms, undergo a worsening in the acute phase but later stabilize, progressing physiologically over years. Finally, there are regions, such as the uncinate fasciculus, which are not altered early in life, but are affected around the onset of schizophrenia, with their impairment continuously worsening over time. Further extensive longitudinal studies are needed to understand the timing and the possible degenerative characteristics of structural impairment associated with schizophrenia.

  16. Discovery of molecular associations among aging, stem cells, and cancer based on gene expression profiling

    Institute of Scientific and Technical Information of China (English)

    Xiaosheng Wang

    2013-01-01

    The emergence of a huge volume of "omics" data enables a computational approach to the investigation of the biology of cancer.The cancer informatics approach is a useful supplement to the traditional experimental approach.I reviewed several reports that used a bioinformatics approach to analyze the associations among aging,stem cells,and cancer by microarray gene expression profiling.The high expression of aging-or human embryonic stem cell-related molecules in cancer suggests that certain important mechanisms are commonly underlying aging,stem cells,and cancer.These mechanisms are involved in cell cycle regulation,metabolic process,DNA damage response,apoptosis,p53 signaling pathway,immune/inflammatory response,and other processes,suggesting that cancer is a developmental and evolutional disease that is strongly related to aging.Moreover,these mechanisms demonstrate that the initiation,proliferation,and metastasis of cancer are associated with the deregulation of stem cells.These findings provide insights into the biology of cancer.Certainly,the findings that are obtained by the informatics approach should be justified by experimental validation.This review also noted that next-generation sequencing data provide enriched sources for cancer informatics study.

  17. Discovery of molecular associations among aging, stem cells, and cancer based on gene expression profiling.

    Science.gov (United States)

    Wang, Xiaosheng

    2013-04-01

    The emergence of a huge volume of "omics" data enables a computational approach to the investigation of the biology of cancer. The cancer informatics approach is a useful supplement to the traditional experimental approach. I reviewed several reports that used a bioinformatics approach to analyze the associations among aging, stem cells, and cancer by microarray gene expression profiling. The high expression of aging- or human embryonic stem cell-related molecules in cancer suggests that certain important mechanisms are commonly underlying aging, stem cells, and cancer. These mechanisms are involved in cell cycle regulation, metabolic process, DNA damage response, apoptosis, p53 signaling pathway, immune/inflammatory response, and other processes, suggesting that cancer is a developmental and evolutional disease that is strongly related to aging. Moreover, these mechanisms demonstrate that the initiation, proliferation, and metastasis of cancer are associated with the deregulation of stem cells. These findings provide insights into the biology of cancer. Certainly, the findings that are obtained by the informatics approach should be justified by experimental validation. This review also noted that next-generation sequencing data provide enriched sources for cancer informatics study.

  18. Natural ageing responses of duplex structured Mg-Li based alloys

    Science.gov (United States)

    Li, C. Q.; Xu, D. K.; Wang, B. J.; Sheng, L. Y.; Qiao, Y. X.; Han, E. H.

    2017-01-01

    Natural ageing responses of duplex structured Mg-6%Li and Mg-6%Li-6%Zn-1.2%Y alloys have been investigated. Microstructural analyses revealed that the precipitation and coarsening process of α-Mg particles could occur in β-Li phases of both two alloys during ageing process. Since a certain amount of Mg atoms in β-Li phases were consumed for the precipitation of abundant tiny MgLiZn particles, the size of α-Mg precipitates in Mg-6%Li-6%Zn-1.2%Y alloy was relatively smaller than that in Mg-6%Li alloy. Micro hardness measurements demonstrated that with the ageing time increasing, the α-Mg phases in Mg-6%Li alloy could have a constant hardness value of 41 HV, but the contained β-Li phases exhibited a slight age-softening response. Compared with the Mg-6%Li alloy, the age-softening response of β-Li phases in Mg-6%Li-6%Zn-1.2%Y alloy was much more profound. Meanwhile, a normal age-hardening response of α-Mg phases was maintained. Tensile results indicated that obvious ageing-softening phenomenon in terms of macro tensile strength occurred in both two alloys. Failure analysis demonstrated that for the Mg-6%Li alloy, cracks were preferentially initiated at α-Mg/β-Li interfaces. For the Mg-6%Li-6%Zn-1.2%Y alloy, cracks occurred at both α-Mg/β-Li interfaces and slip bands in α-Mg and β-Li phases.

  19. Effects of spermatozoa-oviductal cell coincubation time and oviductal cell age on spermatozoa-oviduct interactions.

    Science.gov (United States)

    Aldarmahi, Ahmed; Elliott, Sarah; Russell, Jean; Fazeli, Alireza

    2014-01-01

    The oviduct plays a crucial role in sperm storage, maintenance of sperm viability and sperm transport to the site of fertilisation. The aim of the present study was to investigate the effects of oviductal cell culture passage number, oviductal cell age and spermatozoa-oviduct coincubation times on gene expression in oviductal cells. Immortalised oviductal epithelial cells (OPEC) obtained from two different cell passages (36 and 57) were subcultured three times with and without spermatozoa for 24 h (control group). In a second study, OPEC were cocultured with spermatozoa for different time intervals (0, 4, 12 and 24 h). Expression of adrenomedullin (ADM), heat shock 70 kDa protein 8 (HSPA8) and prostaglandin E synthase (PGES) in OPEC was measured by quantitative polymerase chain reaction. The expression of ADM and HSPA8 was decreased significantly in OPEC cells from Passage 57, particularly in the later subculture group. These effects on HSPA8, but not ADM, expression in OPEC were further altered after coculture with spermatozoa for 24 h. We also demonstrated that spermatozoa-oviduct coculture for 12 and 24 h resulted in significantly higher expression of ADM, HSPA8 and PGES in OPEC. Overall, the data suggest that the OPEC lose some of their properties as a result of oviductal cell aging and that there are spermatozoa-oviduct interactions leading to increased oviductal cell gene expression.

  20. From Ancient Pathways to Aging Cells-Connecting Metabolism and Cellular Senescence.

    Science.gov (United States)

    Wiley, Christopher D; Campisi, Judith

    2016-06-14

    Cellular senescence is a complex stress response that permanently arrests the proliferation of cells at risk for oncogenic transformation. However, senescent cells can also drive phenotypes associated with aging. Although the senescence-associated growth arrest prevents the development of cancer, and the metabolism of cancer cells has been studied in depth, the metabolic causes and consequences of cellular senescence were largely unexplored until recently. New findings reveal key roles for several aspects of cellular metabolism in the establishment and control of senescent phenotypes. These discoveries have important implications for both cancer and aging. In this review, we highlight some of the recent links between metabolism and phenotypes that are commonly associated with senescent cells.

  1. Could Metabolic Syndrome, Lipodystrophy, and Aging Be Mesenchymal Stem Cell Exhaustion Syndromes?

    Directory of Open Access Journals (Sweden)

    Eduardo Mansilla

    2011-01-01

    Full Text Available One of the most important and complex diseases of modern society is metabolic syndrome. This syndrome has not been completely understood, and therefore an effective treatment is not available yet. We propose a possible stem cell mechanism involved in the development of metabolic syndrome. This way of thinking lets us consider also other significant pathologies that could have similar etiopathogenic pathways, like lipodystrophic syndromes, progeria, and aging. All these clinical situations could be the consequence of a progressive and persistent stem cell exhaustion syndrome (SCES. The main outcome of this SCES would be an irreversible loss of the effective regenerative mesenchymal stem cells (MSCs pools. In this way, the normal repairing capacities of the organism could become inefficient. Our point of view could open the possibility for a new strategy of treatment in metabolic syndrome, lipodystrophic syndromes, progeria, and even aging: stem cell therapies.

  2. Prokaryotic cells: structural organisation of the cytoskeleton and organelles

    OpenAIRE

    Wanderley de Souza

    2012-01-01

    For many years, prokaryotic cells were distinguished from eukaryotic cells based on the simplicity of their cytoplasm, in which the presence of organelles and cytoskeletal structures had not been discovered. Based on current knowledge, this review describes the complex components of the prokaryotic cell cytoskeleton, including (i) tubulin homologues composed of FtsZ, BtuA, BtuB and several associated proteins, which play a fundamental role in cell division, (ii) actin-like homologues, such as...

  3. Age-related compaction of lens fibers affects the structure and optical properties of rabbit lenses

    Directory of Open Access Journals (Sweden)

    Al-Ghoul Walid M

    2007-12-01

    Full Text Available Abstract Background The goal of this investigation was to correlate particular age-related structural changes (compaction to the amount of scatter in rabbit lenses and to determine if significant fiber compaction occurred in the nuclear and inner cortical regions. Methods New Zealand White rabbits at 16–20 months old (adult; n = 10 and at 3.5–4 years old (aged; n = 10 were utilized for this study. Immediately after euthanising, scatter was assessed in fresh lenses by low power helium-neon laser scan analysis. Scatter data was analyzed both for whole lenses and regionally, to facilitate correlation with morphometric data. After functional analysis, lenses were fixed and processed for scanning electron microcopy (SEM; right eyes and light microscopy (LM; left eyes. Morphometric analysis of SEM images was utilized to evaluate compaction of nuclear fibers. Similarly, measurements from LM images were used to assess compaction of inner cortical fibers. Results Scatter was significantly greater in aged lenses as compared to adult lenses in all regions analyzed, however the difference in the mean was slightly more pronounced in the inner cortical region. The anterior and posterior elliptical angles at 1 mm (inner fetal nucleus were significantly decreased in aged vs. adult lenses (anterior, p = 0.040; posterior, p = 0.036. However, the average elliptical angles at 2.5 mm (outer fetal nucleus were not significantly different in adult and aged lenses since all lenses examined had comparable angles to inner fetal fibers of aged lenses, i.e. they were all compacted. In cortical fibers, measures of average cross-sectional fiber area were significantly different at diameters of both 6 and 7 mm as a function of age (p = 0.011 and p = 0.005, respectively. Accordingly, the estimated fiber volume was significantly decreased in aged as compared to adult lenses at both 6 mm diameter (p = 0.016 and 7 mm diameter (p = 0.010. Conclusion Morphometric data indicates

  4. Impact of high glucose and AGEs on cultured kidney-derived cells. Effects on cell viability, lysosomal enzymes and effectors of cell signaling pathways.

    Science.gov (United States)

    Peres, Giovani B; Schor, Nestor; Michelacci, Yara M

    2017-04-01

    We have previously reported decreased expression and activities of lysosomal cathepsins B and L in diabetic kidney. Relevant morphological changes were observed in proximal tubules, suggesting that these cells are implicated in the early stages of the disease. The aim of the present study was to investigate the mechanisms that lead to these changes. The effects of high glucose (HG) and advanced glycation end products (AGEs) on cell viability, lysosomal enzymes and other effectors of cell signaling of cultured kidney cells were studied. HG increased viable mesangial cells (ihMC) in 48 h, while epithelial tubular cells were not affected (LLC-PK1 and MDCK). In contrast, the number of viable cells was markedly decreased, for all cell lines, by AGE-BSA. Concerning lysosomal enzymes, the main cysteine-protease expressed by these cells was cathepsin B, and its concentration was much higher in epithelial than in mesangial cells. Exposure to HG had no effect on the cathepsin B activity, but AGE-BSA caused a marked decrease in LLC-PK1, and increased the enzyme activities in the other cell lines. The levels of nitric oxide (NO) was increased by AGE-BSA in all cell lines, suggesting oxidative stress, and Western blotting has shown that, among the investigated proteins, cathepsin B, mTOR and transcription factor EB (TFEB) were the most significantly affected by exposure to AGE-BSA. As mTOR induces anabolism and inhibits autophagy, and TFEB is a master transcription factor for lysosomal enzymes, it is possible that this pathway plays a role in the inhibition of lysosomal enzymes in proximal tubule cells.

  5. Structural response of phyllomanganates to wet aging and aqueous Mn(II)

    Science.gov (United States)

    Hinkle, Margaret A. G.; Flynn, Elaine D.; Catalano, Jeffrey G.

    2016-11-01

    Naturally occurring Mn(IV/III) oxides are often formed through microbial Mn(II) oxidation, resulting in reactive phyllomanganates with varying Mn(IV), Mn(III), and vacancy contents. Residual aqueous Mn(II) may adsorb in the interlayer of phyllomanganates above vacancies in their octahedral sheets. The potential for interlayer Mn(II)-layer Mn(IV) comproportionation reactions and subsequent formation of structural Mn(III) suggests that aqueous Mn(II) may cause phyllomanganate structural changes that alters mineral reactivity or trace metal scavenging. Here we examine the effects of aging phyllomanganates with varying initial vacancy and Mn(III) content in the presence and absence of dissolved Mn(II) at pH 4 and 7. Three phyllomanganates were studied: two exhibiting turbostratic layer stacking (δ-MnO2 with high vacancy content and hexagonal birnessite with both vacancies and Mn(III) substitutions) and one with rotationally ordered layer stacking (triclinic birnessite containing predominantly Mn(III) substitutions). Structural analyses suggest that during aging at pH 4, Mn(II) adsorbs above vacancies and promotes the formation of phyllomanganates with rotationally ordered sheets and mixed symmetries arranged into supercells, while structural Mn(III) undergoes disproportionation. These structural changes at pH 4 correlate with reduced Mn(II) uptake onto triclinic and hexagonal birnessite after 25 days relative to 48 h of reaction, indicating that phyllomanganate reactivity decreases upon aging with Mn(II), or that recrystallization processes involving Mn(II) uptake occur over 25 days. At pH 7, Mn(II) adsorbs and causes limited structural effects, primarily increasing sheet stacking in δ-MnO2. These results show that aging-induced structural changes in phyllomanganates are affected by aqueous Mn(II), pH, and initial solid-phase Mn(III) content. Such restructuring likely alters manganese oxide reactions with other constituents in environmental and geologic systems

  6. Periplasmic Acid Stress Increases Cell Division Asymmetry (Polar Aging of Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Michelle W Clark

    Full Text Available Under certain kinds of cytoplasmic stress, Escherichia coli selectively reproduce by distributing the newer cytoplasmic components to new-pole cells while sequestering older, damaged components in cells inheriting the old pole. This phenomenon is termed polar aging or cell division asymmetry. It is unknown whether cell division asymmetry can arise from a periplasmic stress, such as the stress of extracellular acid, which is mediated by the periplasm. We tested the effect of periplasmic acid stress on growth and division of adherent single cells. We tracked individual cell lineages over five or more generations, using fluorescence microscopy with ratiometric pHluorin to measure cytoplasmic pH. Adherent colonies were perfused continually with LBK medium buffered at pH 6.00 or at pH 7.50; the external pH determines periplasmic pH. In each experiment, cell lineages were mapped to correlate division time, pole age and cell generation number. In colonies perfused at pH 6.0, the cells inheriting the oldest pole divided significantly more slowly than the cells inheriting the newest pole. In colonies perfused at pH 7.50 (near or above cytoplasmic pH, no significant cell division asymmetry was observed. Under both conditions (periplasmic pH 6.0 or pH 7.5 the cells maintained cytoplasmic pH values at 7.2-7.3. No evidence of cytoplasmic protein aggregation was seen. Thus, periplasmic acid stress leads to cell division asymmetry with minimal cytoplasmic stress.

  7. Morphological changes of cell proliferation and apoptosis in rat jejunal mucosa at different ages

    Institute of Scientific and Technical Information of China (English)

    Li Wang; Jian Li; Qing Li; Jian Zhang; Xiang-Lin Duan

    2003-01-01

    AIM: To study the changes of cell proliferation and apoptosis in rat jejunal epithelium at different ages.METHODS: Cell proliferation and apoptosis of the jejunal mucosal and glandulous epithelia from birth to postnatal 12th month were observed using immunocytochemistry (ICC), and TUNEL method. The height of villus, the thickness of muscle layer and the number of goblet cells in jejunal mucosal and glandulous epithelia were measured by BeiHang analytic software and analyzed by STAT.RESULTS: (1) Proliferating cell nuclear antigen (PCNA) positive cells of jejunal glandulous recess were found and increased in number from birth to the postnatal 3rd month. The number of PCNA positive cells peaked in the postnatal 3rd month, and decreased from then on. (2) The number of apoptotic cells also peaked in the postnatal 3rd month, showing a similar trend to that of the PCNA positive cells. (3) The height of jejunal villus increased after birth, peaked in the postnatal 3rd month and decreased from then on. The jejunal muscle layer became thicker in the postnatal 3rd week and the postnatal 12th month.The number of goblet cells of the jejunal mucosal and glandulous epithelia had a linear correlation with age.CONCLUSION: (1) PCNA positive cells are distributed in the jejunal glandulous recess. (2) Apoptotic cell number peaks in the postnatal 3rd month, indicating that cell proliferation and apoptosis are developed with the formation of digestive metabolism as rat grows to maturity. (3) The thickness of jejunal muscle layer increases to a maximum in the postnatal 3rd week, which may be related to the change in diet from milk to solid food. (4) The number of goblet cells increases rapidly in the postnatal 3rd week, probably due to ingestion of solid food.

  8. Stem cell therapies for age-related macular degeneration: the past, present, and future

    Directory of Open Access Journals (Sweden)

    Dang Y

    2015-01-01

    Full Text Available Yalong Dang,1–3 Chun Zhang,1,2 Yu Zhu31Department of Ophthalmology, Peking University Third Hospital, Beijing, People’s Republic of China; 2Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing, People’s Republic of China; 3Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaAbstract: In the developed world, age-related macular degeneration (AMD is one of the major causes of irreversible blindness in the elderly. Although management of neovascular AMD (wet AMD has dramatically progressed, there is still no effective treatment for nonneovascular AMD (dry AMD, which is characterized by retinal pigment epithelial (RPE cell death (or dysfunction and microenvironmental disruption in the retina. Therefore, RPE replacement and microenvironmental regulation represent viable treatments for dry AMD. Recent advances in cell biology have demonstrated that RPE cells can be easily generated from several cell types (pluripotent stem cells, multipotent stem cells, or even somatic cells by spontaneous differentiation, coculturing, defined factors or cell reprogramming, respectively. Additionally, in vivo studies also showed that the restoration of visual function could be obtained by transplanting functional RPE cells into the subretinal space of recipient. More importantly, clinical trials approved by the US government have shown promising prospects in RPE transplantation. However, key issues such as implantation techniques, immune rejection, and xeno-free techniques are still needed to be further investigated. This review will summarize recent advances in cell transplantation for dry AMD. The obstacles and prospects in this field will also be discussed.Keywords: stem cell, age-related macular degeneration, retinal pigment epithelium, cell reprogramming, clinical trial

  9. Reconstitution of naive T cells during antiretroviral treatment of HIV-infected adults is dependent on age

    NARCIS (Netherlands)

    Cohen Stuart, James; Hamann, Dörte; Borleffs, Jan; Roos, Marijke; Miedema, Frank; Boucher, Charles; de Boer, Rob

    2002-01-01

    OBJECTIVE: To determine the influence of age on the regeneration rate of naive and memory T cells in the blood of 45 adults on highly active antiretroviral therapy (HAART). METHODS: The age of the patients ranged from 25 to 57 years. Naive cells were defined as CD45RA+CD27+. Cells negative for CD45R

  10. Augmented vascular smooth muscle cell stiffness and adhesion when hypertension is superimposed on aging.

    Science.gov (United States)

    Sehgel, Nancy L; Sun, Zhe; Hong, Zhongkui; Hunter, William C; Hill, Michael A; Vatner, Dorothy E; Vatner, Stephen F; Meininger, Gerald A

    2015-02-01

    Hypertension and aging are both recognized to increase aortic stiffness, but their interactions are not completely understood. Most previous studies have attributed increased aortic stiffness to changes in extracellular matrix proteins that alter the mechanical properties of the vascular wall. Alternatively, we hypothesized that a significant component of increased vascular stiffness in hypertension is due to changes in the mechanical and adhesive properties of vascular smooth muscle cells, and that aging would augment the contribution from vascular smooth muscle cells when compared with the extracellular matrix. Accordingly, we studied aortic stiffness in young (16-week-old) and old (64-week-old) spontaneously hypertensive rats and Wistar-Kyoto wild-type controls. Systolic and pulse pressures were significantly increased in young spontaneously hypertensive rats when compared with young Wistar-Kyoto rats, and these continued to rise in old spontaneously hypertensive rats when compared with age-matched controls. Excised aortic ring segments exhibited significantly greater elastic moduli in both young and old spontaneously hypertensive rats versus Wistar-Kyoto rats. were isolated from the thoracic aorta, and stiffness and adhesion to fibronectin were measured by atomic force microscopy. Hypertension increased both vascular smooth muscle cell stiffness and vascular smooth muscle cell adhesion, and these increases were both augmented with aging. By contrast, hypertension did not affect histological measures of aortic collagen and elastin, which were predominantly changed by aging. These findings support the concept that stiffness and adhesive properties of vascular smooth muscle cells are novel mechanisms contributing to the increased aortic stiffness occurring with hypertension superimposed on aging.

  11. 77 FR 74883 - Aging Management of Stainless Steel Structures and Components in Treated Borated Water; Revision 1

    Science.gov (United States)

    2012-12-18

    ... COMMISSION Aging Management of Stainless Steel Structures and Components in Treated Borated Water; Revision 1... corrects License Renewal Interim Staff Guidance, LR-ISG-2011-01, ``Aging Management of Stainless Steel Structures and Components in Treated Borated Water,'' which was announced in the Federal Register on May...

  12. Structure-activity analysis of aging and reactivation of human butyrylcholinesterase inhibited by analogues of tabun.

    Science.gov (United States)

    Carletti, Eugénie; Aurbek, Nadine; Gillon, Emilie; Loiodice, Mélanie; Nicolet, Yvain; Fontecilla-Camps, Juan-Carlos; Masson, Patrick; Thiermann, Horst; Nachon, Florian; Worek, Franz

    2009-06-12

    hBChE [human BChE (butyrylcholinesterase)] naturally scavenges OPs (organophosphates). This bioscavenger is currently in Clinical Phase I for pretreatment of OP intoxication. Phosphylated ChEs (cholinesterases) can undergo a spontaneous time-dependent process called 'aging' during which the conjugate is dealkylated, leading to creation of an enzyme that cannot be reactivated. hBChE inhibited by phosphoramidates such as tabun displays a peculiar resistance to oxime-mediated reactivation. We investigated the basis of oxime resistance of phosphoramidyl-BChE conjugates by determining the kinetics of inhibition, reactivation (obidoxime {1,1'-(oxybis-methylene) bis[4-(hydroxyimino) methyl] pyridinium dichloride}, TMB-4 [1,3-trimethylene-bis(4-hydroxyiminomethylpyridinium) dibromide], HLö 7 {1-[[[4-(aminocarbonyl) pyridinio]methoxy]methyl]-2,4-bis-[(hydroxyimino)methyl] pyridinium dimethanesulfonate)}, HI-6 {1-[[[4-(aminocarbonyl) pyridinio] methoxy] methyl]-2-[(hydroxyimino)methyl]pyridinium dichloride monohydrate} and aging, and the crystal structures of hBChE inhibited by different N-monoalkyl and N,N-dialkyl tabun analogues. The refined structures of aged hBChE conjugates show that aging proceeds through O-dealkylation of the P(R) enantiomer of N,N-diethyl and N-propyl analogues, with subsequent formation of a salt bridge preventing reactivation, similarly to a previous observation made on tabun-ChE conjugates. Interestingly, the N-methyl analogue projects its amino group towards the choline-binding pocket, so that aging proceeds through deamination. This orientation results from a preference of hBChE's acyl-binding pocket for larger than 2-atoms linear substituents. The correlation between the inhibitory potency and the N-monoalkyl chain length is related to increasingly optimized interactions with the acyl-binding pocket as shown by the X-ray structures. These kinetics and X-ray data lead to a structure-activity relationship that highlights steric and electronic

  13. Nontargeted metabolomics approach for age differentiation and structure interpretation of age-dependent key constituents in hairy roots of Panax ginseng.

    Science.gov (United States)

    Kim, Nahyun; Kim, Kemok; Lee, Donghyuk; Shin, Yoo-Soo; Bang, Kyong-Hwan; Cha, Seon-Woo; Lee, Jae Won; Choi, Hyung-Kyoon; Hwang, Bang Yeon; Lee, Dongho

    2012-10-26

    The age of the ginseng plant has been considered as an important criterion to determine the quality of this species. For age differentiation and structure interpretation of age-dependent key constituents of Panax ginseng, hairy root (fine root) extracts aged from four to six years were analyzed using a nontargeted approach with ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS). Various classification methods were used to determine an optimal method to best describe ginseng age by selecting influential metabolites of different ages. Through the metabolite selection process, several age-dependent key constituents having the potential to be biomarkers were determined, and their structures were identified according to tandem mass spectrometry and accurate mass spectrometry by comparing them with an in-house ginsenoside library and with literature data. This proposed method applied to the hairy roots of P. ginseng showed an improved efficiency of age differentiation when compared to previous results on the main roots and increases the possibility of the identification of key metabolites that can be used as biomarker candidates for quality assurance in ginseng.

  14. Age-related decrease in rod bipolar cell density of the human retina: an immunohistochemical study

    Indian Academy of Sciences (India)

    P Aggarwal; T C Nag; S Wadhwa

    2007-03-01

    During normal ageing, the rods (and other neurones) undergo a significant decrease in density in the human retina from the fourth decade of life onward. Since the rods synapse with the rod bipolar cells in the outer plexiform layer, a decline in rod density (mainly due to death) may ultimately cause an associated decline of the neurones which, like the rod bipolar cells, are connected to them. The rod bipolar cells are selectively stained with antibodies to protein kinase C-. This study examined if rod bipolar cell density changes with ageing of the retina, utilizing donor human eyes (age: 6–91 years). The retinas were fixed and their temporal parts from the macula to the mid-periphery sectioned and processed for protein kinase C- immunohistochemistry. The density of the immunopositive rod bipolar cells was estimated in the mid-peripheral retina (eccentricity: 3–5 mm) along the horizontal temporal axis. The results show that while there is little change in the density of the rod bipolar cells from 6 to 35 years (2.2%), the decline during the period from 35 to 62 years is about 21% and between seventh and tenth decades, it is approximately 27%.

  15. Age-Dependent Defects of Regulatory B Cells in Wiskott-Aldrich Syndrome Gene Knockout Mice.

    Directory of Open Access Journals (Sweden)

    Tadafumi Yokoyama

    Full Text Available The Wiskott-Aldrich syndrome (WAS is a rare X-linked primary immunodeficiency characterized by recurrent infections, thrombocytopenia, eczema, and high incidence of malignancy and autoimmunity. The cellular mechanisms underlying autoimmune complications in WAS have been extensively studied; however, they remain incompletely defined. We investigated the characteristics of IL-10-producing CD19+CD1dhighCD5+ B cells (CD1dhighCD5+ Breg obtained from Was gene knockout (WKO mice and found that their numbers were significantly lower in these mice compared to wild type (WT controls. Moreover, we found a significant age-dependent reduction of the percentage of IL-10-expressing cells in WKO CD1dhighCD5+ Breg cells as compared to age-matched WT control mice. CD1dhighCD5+ Breg cells from older WKO mice did not suppress the in vitro production of inflammatory cytokines from activated CD4+ T cells. Interestingly, CD1dhighCD5+ Breg cells from older WKO mice displayed a basal activated phenotype which may prevent normal cellular responses, among which is the expression of IL-10. These defects may contribute to the susceptibility to autoimmunity with age in patients with WAS.

  16. Cell-autonomous mechanisms of chronological aging in the yeast Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Anthony Arlia-Ciommo

    2014-05-01

    Full Text Available A body of evidence supports the view that the signaling pathways governing cellular aging – as well as mechanisms of their modulation by longevity-extending genetic, dietary and pharmacological interventions - are conserved across species. The scope of this review is to critically analyze recent advances in our understanding of cell-autonomous mechanisms of chronological aging in the budding yeast Saccharomyces cerevisiae. Based on our analysis, we propose a concept of a biomolecular network underlying the chronology of cellular aging in yeast. The concept posits that such network progresses through a series of lifespan checkpoints. At each of these checkpoints, the intracellular concentrations of some key intermediates and products of certain metabolic pathways - as well as the rates of coordinated flow of such metabolites within an intricate network of intercompartmental communications - are monitored by some checkpoint-specific ′′master regulator′′ proteins. The concept envisions that a synergistic action of these master regulator proteins at certain early-life and late-life checkpoints modulates the rates and efficiencies of progression of such processes as cell metabolism, growth, proliferation, stress resistance, macromolecular homeostasis, survival and death. The concept predicts that, by modulating these vital cellular processes throughout lifespan (i.e., prior to an arrest of cell growth and division, and following such arrest, the checkpoint-specific master regulator proteins orchestrate the development and maintenance of a pro- or anti-aging cellular pattern and, thus, define longevity of chronologically aging yeast.

  17. Amount of cells of diffuse lymphoid tissue of uterine tube in women of different age groups

    Directory of Open Access Journals (Sweden)

    S.V. Shadlinskaya

    2010-06-01

    Full Text Available The aim of the investigation was to study the amount of lymphoid cells of diffuse lymphoid tissue of uterine tube in women of different age. The transverse sections of one-third of each part of uterine tube from 116 women (from newborn to senile age were studied. The sections were colored by gematoksilin-eosin, by van Gizon, by Brashe, azur-2-eosine, by Qrimelius. The amount of lymphoid cells of diffuse lymphoid tissue of uterine tube increased till the age of 16-20 and remained at high level further on till the age of 35. The quantity of lymphoid cells of diffuse lymphoid tissue of uterine tube changed according to the age and localization throughout the organ. The presence of diffused lymphoid tissue of uterine tube depended on the state of reproductive function of female organism. In the phase of desquamation there was minimal quantity of lymphoid tissue and in the phase of secretion there was maximal quantity of lymphoid tissue

  18. Flexible PCPDTBT:PCBM solar cells with integrated grating structures

    DEFF Research Database (Denmark)

    Oliveira Hansen, Roana Melina de; Liu, Yinghui; Madsen, Morten;

    2013-01-01

    spectra of the active layer. This optimized solar cell structure leads to an enhanced absorption in the active layer and thus improved short-circuit currents and power conversion efficiencies in the fabricated devices. Fabrication of the solar cells on thin polyimide substrates which are compatible......We report on development of flexible PCPDTBT:PCBM solar cells with integrated diffraction gratings on the bottom electrodes. The presented results address PCPDTBT:PCBM solar cells in an inverted geometry, which contains implemented grating structures whose pitch is tuned to match the absorption...

  19. Paternal age and telomere length in twins: the germ stem cell selection paradigm.

    Science.gov (United States)

    Hjelmborg, Jacob B; Dalgård, Christine; Mangino, Massimo; Spector, Tim D; Halekoh, Ulrich; Möller, Sören; Kimura, Masayuki; Horvath, Kent; Kark, Jeremy D; Christensen, Kaare; Kyvik, Kirsten O; Aviv, Abraham

    2015-08-01

    Telomere length, a highly heritable trait, is longer in offspring of older fathers. This perplexing feature has been attributed to the longer telomeres in sperm of older men and it might be an 'epigenetic' mechanism through which paternal age plays a role in telomere length regulation in humans. Based on two independent (discovery and replication) twin studies, comprising 889 twin pairs, we show an increase in the resemblance of leukocyte telomere length between dizygotic twins of older fathers, which is not seen in monozygotic twins. This phenomenon might result from a paternal age-dependent germ stem cell selection process, whereby the selected stem cells have longer telomeres, are more homogenous with respect to telomere length, and share resistance to aging.

  20. Impaired T-cell functions in aged guinea-pigs restored by thymostimulin (TS).

    Science.gov (United States)

    Falchetti, R; Cafiero, C; Caprino, L

    1982-01-01

    The age-related changes of different T-cell activities in guinea pigs and the effect of Thymostimulin (TS), a thymus extract, on the immunocompetence of these cells was studied. Mitogen-induced proliferation of peripheral blood lymphocytes was increased by TS in vitro. The intraperitoneal administration of TS (5 mg/kg) to aged animals restored the helper function of T lymphocytes and enhanced the reactivity to mitogens of both peripheral blood lymphocytes and spleen lymphocytes. The data obtained suggest that as in other species, there is an age-associated decline of immunological response, in guinea pigs too, probably due to a deficiency of thymic hormone(s) and that TS could correct this deficiency.

  1. Nampt Expression Decreases Age-Related Senescence in Rat Bone Marrow Mesenchymal Stem Cells by Targeting Sirt1

    Science.gov (United States)

    Ma, Cao; Pi, Chenchen; Yang, Yue; Lin, Lin; Shi, Yingai; Li, Yan; Li, Yulin; He, Xu

    2017-01-01

    Senescence restricts the development of applications involving mesenchymal stem cells (MSCs) in research fields, such as tissue engineering, and stem cell therapeutic strategies. Understanding the mechanisms underlying natural aging processes may contribute to the development of novel approaches to preventing age-related diseases or slowing individual aging processes. Nampt is a rate-limiting NAD biosynthetic enzyme that plays critical roles in energy metabolism, cell senescence and maintaining life spans. However, it remains unknown whether Nampt influences stem cell senescence. In this study, the function of Nampt was investigated using a rat model of natural aging. Our data show that Nampt expression was significantly lower in MSCs obtained from aged rats than in those obtained from young rats during physiological aging. Reducing the level of Nampt in aged MSCs resulted in lower intracellular concentrations of NAD+ and downregulated Sirt1 expression and activity. After the Nampt inhibitor FK866 was added, young MSCs were induced to become aged cells. The enhanced senescence was correlated with NAD+ depletion and Sirt1 activity attenuation. In addition, Nampt overexpression attenuated cell senescence in aged MSCs. Our findings provide a new explanation for the mechanisms underlying stem cell senescence and a novel target for delaying stem cell senescence and preventing and treating age-related diseases. PMID:28125705

  2. Age of language learning shapes brain structure: a cortical thickness study of bilingual and monolingual individuals.

    Science.gov (United States)

    Klein, Denise; Mok, Kelvin; Chen, Jen-Kai; Watkins, Kate E

    2014-04-01

    We examined the effects of learning a second language (L2) on brain structure. Cortical thickness was measured in the MRI datasets of 22 monolinguals and 66 bilinguals. Some bilingual subjects had learned both languages simultaneously (0-3 years) while some had learned their L2 after achieving proficiency in their first language during either early (4-7 years) or late childhood (8-13 years). Later acquisition of L2 was associated with significantly thicker cortex in the left inferior frontal gyrus (IFG) and thinner cortex in the right IFG. These effects were seen in the group comparisons of monolinguals, simultaneous bilinguals and early and late bilinguals. Within the bilingual group, significant correlations between age of acquisition of L2 and cortical thickness were seen in the same regions: cortical thickness correlated with age of acquisition positively in the left IFG and negatively in the right IFG. Interestingly, the monolinguals and simultaneous bilinguals did not differ in cortical thickness in any region. Our results show that learning a second language after gaining proficiency in the first language modifies brain structure in an age-dependent manner whereas simultaneous acquisition of two languages has no additional effect on brain development.

  3. Morphogenetic and structural characteristics of tillers of guinea grass of different age and grazing severities

    Directory of Open Access Journals (Sweden)

    Denise Baptaglin Montagner

    2011-10-01

    Full Text Available The objective of this research was to evaluate the effects of tiller age on morphogenic and structural characteristics of guinea grass cv. Mombaca subjected to intermittent stocking and three stubble heights: 30 cm, 50 cm and 50-30 cm. Stubble heights were assigned to experimental units in a completely randomized block design with three replicates. Grazing was performed when canopy intercepted 95% of light incidence. Leaf appearance rate, leaf elongation rate and number of live leaves per tiller were higher in the summer when compared with the winter. Contrarily, stem elongation rate, phyllochron and leaf lifespan were lower in the summer when compared with the winter. During the summer, young tillers had higher leaf appearance and elongation rates when compared with the older ones. Young and mature tillers had the highest values of live leaves per tiller in the summer. There was no difference between summer and winter for the final length of leaf blade between tillers of the same age, except in mature tillers, which had higher final leaf length during the summer. Senescence rate of leaves was higher in young tillers, followed by mature and old tillers. Age of tiller affects morphogenic and structural characteristics of pasture, showing that young tillers have better growth compared with mature and old tillers

  4. Impact of NBTI Aging on the Single-Event Upset of SRAM Cells

    CERN Document Server

    Bagatin, M; Gerardin, Simone; Paccagnella, Alessandro; Bagatin, Marta

    2010-01-01

    We analyzed the impact of negative bias temperature instability (NBTI) on the single-event upset rate of SRAM cells through experiments and SPICE simulations. We performed critical charge simulations introducing different degradation patterns in the cells, in three technology nodes, from 180 to 90 nm. The simulations results were checked with alpha-particle and heavy-ion irradiations on a 130-nm technology. Both simulations and experimental results show that NBTI degradation does not significantly affect the single-event upset SRAM cell rate as long as the parametric drift induced by aging is within 10\\%.

  5. Age-dependent change in biological characteristics of stem cells in radiation-induced mammary carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Shimada, Yoshiya; Nishimura, Mayumi; Kakinuma, Shizuko; Imaoka, Tatsuhiko [National Institute of Radiological Sciences, Anagawa, Chiba (Japan); Yasukawa-Barnes, Jane; Gould, Michael N.; Clifton, Kelly H. [Univ. of Wisconsin, Department of Human Oncology, Madison, WI (United States)

    2003-07-01

    If you ask what types of cells are the targets for carcinogenesis, a popular answer would be that cancer arises from stem cells. Stem cells are cells that are capable of both self-renewal and generation of differentiated progenies. If the hypothesis of 'cancer as stem cell disease' is correct, the risk of carcinogenesis should be a function of the number of stem cells and their responsiveness of carcinogen-induced damage. In the present study, we addressed the feasibility of this hypothesis using the rat mammary carcinogenesis model. One of the important conclusions emerging from studies on atomic bomb survivors concerns age-related changes in the susceptibility to breast cancer. The relative risk of breast cancer is very high among women exposed to ionizing radiation before or during puberty, and it decreases thereafter. Little information is available, however, on age-related changes in the radiobiological nature of mammary stem cells. We examined age-associated changes in the number of mammary stem-like cells (clonogens) and their susceptibility to radiation in terms of cell death and carcinogenic initiation frequency. The results were as follows. (1) During the prepubertal period, the total number of mammary clonogens per rat increased exponentially with a population doubling time of {approx}4 days. After puberty, the doubling time lengthened to {approx}30 days. The total number of clonogens in abdominal and inguinal mammary glands was {approx}200 in 2-week-old rats, while it was {approx}5600 in 8-week-old rats. (2) The survival curves of clonogenic cells after irradiation indicated that radiation sensitivity of the cells before and during puberty was much higher than after puberty. (3) The initiation frequency of the clonogens from prepubertal rats after 5 Gy irradiation was four times higher than that of the clonogens from post-pubertal rats. These results suggest that changes in the number of stem cells and their radiobiological characteristics

  6. Investigation of Temperature and Aging Effects in Nanostructured Dye Solar Cells Studied by Electrochemical Impedance Spectroscopy

    Directory of Open Access Journals (Sweden)

    Minna Toivola

    2009-01-01

    Full Text Available Effects of aging and cyclically varying temperature on the electrical parameters of dye solar cells were analyzed with electrochemical impedance spectroscopy. Photoelectrode total resistance increased as a function of time due to increasing electron transport resistance in the TiO2 film. On the other hand, photoelectrode recombination resistance was generally larger, electron lifetimes in the TiO2 were film longer, and charge transfer resistance on the counter electrode was smaller after the temperature treatments than before them. These effects correlated with the slower deterioration rate of the temperature-treated cells, in comparison to the reference cells.

  7. Death mode-dependent reduction in succinate dehydrogenase activity in hair cells of aging rat cochleae

    Institute of Scientific and Technical Information of China (English)

    YANG Wei-ping; HU Bo-hua; SUN Jian-he; ZHAI Suo-qiang; Donald Henderson

    2010-01-01

    Background Our previous studies have shown that both apoptosis and necrosis are involved in hair cell (HC) pathogenesis in aging cochleae. To better understand the biological mechanisms responsible for the regulation of HC death, we examined the activity of succinate dehydrogenase (SDH), a mitochondrial bioenergetic enzyme, in the HCs of aging cochleae.Methods The auditory brainstem response thresholds elicited by tone bursts at 4, 10 and 20 kHz were measured in both young (2-3 months) and aging (22-23 months) Wistar rats. SDH activity was evaluated with a colorimetric assay using nitroblue tetrazolium monosodium salt. The SDH-labeled organs of Corti were double stained with propidium iodide, a DNA intercalating fluorescent probe for illustration of HC nuclei. All the specimens were examined with fluorescence microscopy and confocal microscopy.Results Aging rats exhibited a significant elevation of ABR thresholds with threshold shifts being 34 dB at 20 kHz, 28 dB at 10 kHz, and 25 dB at 4 kHz. Consistent with the reduction in the cochlear function, aging cochleae exhibited the reduction of SDH staining intensity in the apical and the basal ends of the cochleae, where a large number of apoptotic, necrotic, and missing HCs were evident. The reduction in SDH staining appeared in a cell-death-mode dependent fashion. Specifically, SDH labeling remained in apoptotic HCs. In contrast, SDH staining was markedly reduced or absent in necrotic HCs.Conclusions In the aging cochlea, SDH activity is preserved in HCs undergoing apoptosis, but is substantially reduced in necrosis. These results suggest that mitochondrial energetic function is involved in the regulation of cell death pathways in the pathogenesis of aging cochleae.

  8. Normalization of Reverse Transcription Quantitative PCR Data During Ageing in Distinct Cerebral Structures.

    Science.gov (United States)

    Bruckert, G; Vivien, D; Docagne, F; Roussel, B D

    2016-04-01

    Reverse transcription quantitative-polymerase chain reaction (RT-qPCR) has become a routine method in many laboratories. Normalization of data from experimental conditions is critical for data processing and is usually achieved by the use of a single reference gene. Nevertheless, as pointed by the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines, several reference genes should be used for reliable normalization. Ageing is a physiological process that results in a decline of many expressed genes. Reliable normalization of RT-qPCR data becomes crucial when studying ageing. Here, we propose a RT-qPCR study from four mouse brain regions (cortex, hippocampus, striatum and cerebellum) at different ages (from 8 weeks to 22 months) in which we studied the expression of nine commonly used reference genes. With the use of two different algorithms, we found that all brain structures need at least two genes for a good normalization step. We propose specific pairs of gene for efficient data normalization in the four brain regions studied. These results underline the importance of reliable reference genes for specific brain regions in ageing.

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

    Science.gov (United States)

    Hanafiah, Hazlenah; Jemain, Abdul Aziz

    2013-11-01

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

  10. Age-Based Comparison of Human Dendritic Spine Structure Using Complete Three-Dimensional Reconstructions

    Science.gov (United States)

    Benavides-Piccione, Ruth; Fernaud-Espinosa, Isabel; Robles, Victor; Yuste, Rafael; DeFelipe, Javier

    2013-01-01

    Dendritic spines of pyramidal neurons are targets of most excitatory synapses in the cerebral cortex. Recent evidence suggests that the morphology of the dendritic spine could determine its synaptic strength and learning rules. However, unfortunately, there are scant data available regarding the detailed morphology of these structures for the human cerebral cortex. In the present study, we analyzed over 8900 individual dendritic spines that were completely 3D reconstructed along the length of apical and basal dendrites of layer III pyramidal neurons in the cingulate cortex of 2 male humans (aged 40 and 85 years old), using intracellular injections of Lucifer Yellow in fixed tissue. We assembled a large, quantitative database, which revealed a major reduction in spine densities in the aged case. Specifically, small and short spines of basal dendrites and long spines of apical dendrites were lost, regardless of the distance from the soma. Given the age difference between the cases, our results suggest selective alterations in spines with aging in humans and indicate that the spine volume and length are regulated by different biological mechanisms. PMID:22710613

  11. Relationships between brain metabolism decrease in normal aging and changes in structural and functional connectivity.

    Science.gov (United States)

    Chételat, Gaël; Landeau, Brigitte; Salmon, Eric; Yakushev, Igor; Bahri, Mohamed Ali; Mézenge, Florence; Perrotin, Audrey; Bastin, Christine; Manrique, Alain; Scheurich, Armin; Scheckenberger, Mathias; Desgranges, Béatrice; Eustache, Francis; Fellgiebel, Andreas

    2013-08-01

    Normal aging is characterized by brain glucose metabolism decline predominantly in the prefrontal cortex. The goal of the present study was to assess whether this change was associated with age-related alteration of white matter (WM) structural integrity and/or functional connectivity. FDG-PET data from 40 young and 57 elderly healthy participants from two research centers (n=49/48 in Center 1/2) were analyzed. WM volume from T1-weighted MRI (Center 1), fractional anisotropy from diffusion-tensor imaging (Center 2), and resting-state fMRI data (Center 1) were also obtained. Group comparisons were performed within each imaging modality. Then, positive correlations were assessed, within the elderly, between metabolism in the most affected region and the other neuroimaging modalities. Metabolism decline in the elderly predominated in the left inferior frontal junction (LIFJ). LIFJ hypometabolism was significantly associated with macrostructural and microstructural WM disturbances in long association fronto-temporo-occipital fibers, while no relationship was found with functional connectivity. The findings offer new perspectives to understand normal aging processes and open avenues for future studies to explore causality between age-related metabolism and connectivity changes.

  12. Macro- and micro-structural white matter differences correlate with cognitive performance in healthy aging.

    Science.gov (United States)

    Marques, Paulo César Gonçalves; Soares, José Miguel Montenegro; Magalhães, Ricardo José da Silva; Santos, Nadine Correia; Sousa, Nuno Jorge Carvalho

    2016-03-01

    Studies have shown that white matter (WM) volumetric reductions and overall degradation occur with aging. Nonetheless little is known about the WM alterations that may underlie different cognitive status in older individuals. The main goal of the present work was to identify and characterize possible macro and microstructural WM alterations that could distinguish between older healthy individuals with contrasting cognitive profiles (i.e., "poor" vs "good" cognitive performers). Structural and diffusion magnetic resonance imaging was performed in order to quantify local WM volumes, white matter signal abnormalities (WMSA) volume (a measure of lesion burden) and diffusion tensor imaging scalar maps known to probe WM microstructure. A battery of neurocognitive/psychological tests was administered to assess the cognitive performance. Poor performers showed a higher slope for the positive association between WMSA volume and age compared to good performers. Even when controlling for WMSA volume, poor performers also evidenced lower fractional anisotropy, as well as positive associations with age with higher slopes of regression parameters in radial and axial diffusivity. Altogether results suggest that cognitive performance is related to differences in WM, with poor cognitive performers displaying signs of faster aging in WM.

  13. Structural and functional connectivity in healthy aging: Associations for cognition and motor behavior.

    Science.gov (United States)

    Hirsiger, Sarah; Koppelmans, Vincent; Mérillat, Susan; Liem, Franziskus; Erdeniz, Burak; Seidler, Rachael D; Jäncke, Lutz

    2016-03-01

    Age-related behavioral declines may be the result of deterioration of white matter tracts, affecting brain structural (SC) and functional connectivity (FC) during resting state. To date, it is not clear if the combination of SC and FC data could better predict cognitive/motor performance than each measure separately. We probed these relationships in the cingulum bundle, a major white matter pathway of the default mode network. We aimed to attain deeper knowledge about: (a) the relationship between age and the cingulum's SC and FC strength, (b) the association between SC and FC, and particularly (c) how the cingulum's SC and FC are related to cognitive/motor performance separately and combined. We examined these associations in a healthy and well-educated sample of 165 older participants (aged 64-85). SC and FC were acquired using probabilistic tractography to derive measures to capture white matter integrity within the cingulum bundle (fractional anisotropy, mean, axial and radial diffusivity) and a seed-based resting-state functional MRI correlation approach, respectively. Participants performed cognitive tests measuring processing speed, memory and executive functions, and motor tests measuring motor speed and grip force. Our data revealed that only SC but not resting state FC was significantly associated with age. Further, the cingulum's SC and FC showed no relation. Different relationships between cognitive/motor performance and SC/FC separately were found, but no additive effect of the combined analysis of cingulum's SC and FC for predicting cognitive/motor performance was apparent.

  14. Structural conformation and leaching from in vitro aged and retrieved Invisalign appliances.

    Science.gov (United States)

    Schuster, Susan; Eliades, George; Zinelis, Spiros; Eliades, Theodore; Bradley, T Gerard

    2004-12-01

    The objectives of this study were to investigate the structure of Invisalign appliances (Align Technology, Santa Clara, Calif) after intraoral exposure, and to qualitatively and quantitatively characterize the substances leached from the aligners after accelerated in vitro aging. Samples of Invisalign appliances were randomly selected from 10 patients before intraoral placement and after retrieval, and the prepared specimens were subjected to (1) bright-field optical reflection microscopy to study the surface morphology; (2) Fourier transform infrared microspectroscopy to characterize the in vivo changes in molecular composition induced on appliance surfaces, (3) scanning electron microscopy and energy dispersive X-ray microanalysis to identify the elemental composition of integuments formed on the surface, and (4) Vickers hardness (HV 200) testing. Another set of reference and retrieved appliances was subjected to artificial aging for 2 weeks, and the extracts were subjected to gas chromatography-mass spectroscopy. The retrieved appliances demonstrated substantial morphological variation relative to the as-received specimens involving abrasion at the cusp tips, adsorption of integuments, and localized calcification of the precipitated biofilm at stagnation sites. Buccal segments of retrieved appliances showed an increase in hardness, which might be attributed to mastication-induced cold work; however, the clinical implication of this effect on mechanotherapy is unknown. In vitro aged and retrieved appliances were found to leach no traceable amount of substances in an ethanol aging solution.

  15. Systematic aging of commercial LiFePO4|Graphite cylindrical cells including a theory explaining rise of capacity during aging

    Science.gov (United States)

    Lewerenz, Meinert; Münnix, Jens; Schmalstieg, Johannes; Käbitz, Stefan; Knips, Marcus; Sauer, Dirk Uwe

    2017-03-01

    The contribution introduces a new theory explaining the capacity increase that is often observed in early stages of life of lithium-ion batteries. This reversible and SOC-depending capacity rise is explained by the passive electrode effect in this work. The theory assumes a slow, compensating flow of active lithium between the passive and the active part of the anode, where the passive part represents the geometric excess anode with respect to the cathode. The theory is validated using a systematic test of 50 cylindrical 8 Ah LiFePO4|Graphite battery cells analyzed during cyclic and calendaric aging. The cyclic aging has been performed symmetrically at 40 °C cell temperature, varying current rates and DODs. The calendar aging is executed at three temperatures and up to four SOCs. The aging is dominated by capacity fade while the increase of internal resistance is hardly influenced. Surprisingly shallow cycling between 45 and 55% SOC shows stronger aging than aging at higher DOD and tests at 4 C exhibit less aging than aging at lower C-rates. Aging mechanisms at 60 °C seem to deviate from those at 40 °C or lower. The data of this aging matrix is used for further destructive and non-destructive characterization in future contributions.

  16. Maintenance of osteoblastic and adipocytic differentiation potential with age and osteoporosis in human marrow stromal cell cultures

    DEFF Research Database (Denmark)

    Justesen, J; Dokkedahl, Karin Stenderup; Eriksen, E F

    2002-01-01

    Osteoblasts and adipocytes share a common precursor cell in the bone marrow stroma, termed marrow stromal cell (MSC). As the volume of bone adipose tissue increases in vivo with age, we hypothesized that decreased bone formation observed during aging and in patients with osteoporosis (OP) is the ......Osteoblasts and adipocytes share a common precursor cell in the bone marrow stroma, termed marrow stromal cell (MSC). As the volume of bone adipose tissue increases in vivo with age, we hypothesized that decreased bone formation observed during aging and in patients with osteoporosis (OP...

  17. Immunofluorescent Analysis of Testicular Biopsies with Germ Cell and Sertoli Cell Markers Shows Significant MVH Negative Germ Cell Depletion with Older Age at Orchiopexy

    DEFF Research Database (Denmark)

    Li, Ruili; Thorup, Jorgen; Sun, Cong;

    2014-01-01

    Undescended testis is the most common defect in male newborns. This condition is associated with increased risks of infertility and testicular malignancy due to abnormal germ cell development in the testes. Early surgery may limit such risks. We analyzed germ cell development vs age at orchiopexy...

  18. Selected Activities of Citrus Maxima Merr. Fruits on Human Endothelial Cells: Enhancing Cell Migration and Delaying Cellular Aging

    Directory of Open Access Journals (Sweden)

    Paiwan Buachan

    2014-04-01

    Full Text Available Endothelial injury and damage as well as accumulated reactive oxygen species (ROS in aging play a significant role in the development of cardiovascular disease (CVD. Recent studies show an association of high citrus fruit intake with a lower risk of CVD and stroke but the mechanisms involved are not fully understood. This study investigated the effects of pummelo (Citrus maxima Merr. var. Tubtim Siam, CM fruit extract on human umbilical vein endothelial cell (HUVECs migration and aging. The freeze-dried powder of fruit extract was characterized for antioxidant capacity (FRAP assay and certain natural antioxidants, including ascorbic acid, gallic acid, hesperidin, and naringin (HPLC. Short-term (48 h co-cultivation of HUVECs with CM enhanced cell migration as evaluated by a scratch wound assay and Boyden chamber assay. A long-term treatment with CM for 35 days significantly increased HUVEC proliferation capability as indicated by population doubling level (PDL. CM also delayed the onset of aging phenotype shown by senescence-associated β-galactosidase (SA-β-gal staining. Furthermore, CM was able to attenuate increased ROS levels in aged cells when determined by 2′,7′-dichlorodihydrofluorescein diacetate (DCDHF while eNOS mRNA expression was increased but the eNOS protein level was not changed. Thus, further in vivo and clinical studies are warranted to support the use of pummelo as a functional fruit for endothelial health and CVD risk reduction.

  19. Influence of age on rat bone-marrow mesenchymal stem cells potential.

    Science.gov (United States)

    Fafián-Labora, J; Fernández-Pernas, P; Fuentes, I; De Toro, J; Oreiro, N; Sangiao-Alvarellos, S; Mateos, J; Arufe, M C

    2015-11-19

    Mesenchymal stem cells promising role in cell-based therapies and tissue engineering appears to be limited due to a decline of their regenerative potential with increasing donor age. Six age groups from bone marrow mesenchymal stem cells of Wistar rats were studied (newborn, infant, young, pre-pubertal, pubertal and adult). Quantitative proteomic assay was performance by iTRAQ using an 8-plex iTRAQ labeling and the proteins differentially expressed were grouped in pluripotency, proliferative and metabolism processes. Proliferation makers, CD117 and Ki67 were measure by flow cytometry assay. Real time polymerase chain reaction analysis of pluripotency markers Rex1, Oct4, Sox2 and Nanog were done. Biological differentiation was realized using specific mediums for 14 days to induce osteogenesis, adipogenesis or chondrogenesis and immunostain analysis of differentiated cell resulting were done. Enzimoimmunoassay analysis of several enzymes as L-lactate dehydrogenase and glucose-6-phosphate isomerase were also done to validate iTRAQ data. Taking together these results indicate for the first time that mesenchymal stem cells have significant differences in their proliferative, pluripotency and metabolism profiles and those differences are age depending.

  20. Using measures of single-cell physiology and physiological state to understand organismic aging.

    Science.gov (United States)

    Mendenhall, Alexander; Driscoll, Monica; Brent, Roger

    2016-02-01

    Genetically identical organisms in homogeneous environments have different lifespans and healthspans. These differences are often attributed to stochastic events, such as mutations and 'epimutations', changes in DNA methylation and chromatin that change gene function and expression. But work in the last 10 years has revealed differences in lifespan- and health-related phenotypes that are not caused by lasting changes in DNA or identified by modifications to DNA or chromatin. This work has demonstrated persistent differences in single-cell and whole-organism physiological states operationally defined by values of reporter gene signals in living cells. While some single-cell states, for example, responses to oxygen deprivation, were defined previously, others, such as a generally heightened ability to make proteins, were, revealed by direct experiment only recently, and are not well understood. Here, we review technical progress that promises to greatly increase the number of these measurable single-cell physiological variables and measureable states. We discuss concepts that facilitate use of single-cell measurements to provide insight into physiological states and state transitions. We assert that researchers will use this information to relate cell level physiological readouts to whole-organism outcomes, to stratify aging populations into groups based on different physiologies, to define biomarkers predictive of outcomes, and to shed light on the molecular processes that bring about different individual physiologies. For these reasons, quantitative study of single-cell physiological variables and state transitions should provide a valuable complement to genetic and molecular explanations of how organisms age.

  1. Crystalline structures in human pancreatic beta cell adenoma.

    Science.gov (United States)

    Mori, H; Kawai, T; Tanaka, T; Fujii, M; Takahashi, M; Miyashita, T

    1978-05-01

    An electron microscopic observation on a pancreatic tumor removed from a 34-year-old woman revealed the fine structural morphology of a functional beta cell adenoma. Characteristic PAS positive crystalline structures were frequently observed in the cytoplasm of the tumor cells. They were not bounded by a membrane and had a rectangular or irregular hexagonal shape. Highly regular patterns were seen as such as lattice or honeycomb and parallel ripple structures. They are similar to the Reinke's crystal or crystalline structures reported in human hepatocytes suffering from several different diseases and considered as a protein-carbohydrate complex. Occasionally, small paracrystalline structures appeared to indicate an immature type of these structures in the opaque fine fibrillar mass. Crystalline or paracrystalline structures were not detected in the normal pancreatic tissue removed with the tumor from the patient.

  2. High glucose induced alteration of SIRTs in endothelial cells causes rapid aging in a p300 and FOXO regulated pathway.

    Directory of Open Access Journals (Sweden)

    Rokhsana Mortuza

    Full Text Available In diabetes, some of the cellular changes are similar to aging. We hypothesized that hyperglycemia accelerates aging-like changes in the endothelial cells (ECs and tissues leading to structural and functional damage. We investigated glucose-induced aging in 3 types of ECs using senescence associated β-gal (SA β-gal staining and cell morphology. Alterations of sirtuins (SIRTs and their downstream mediator FOXO and oxidative stress were investigated. Relationship of such alteration with histone acetylase (HAT p300 was examined. Similar examinations were performed in tissues of diabetic animals. ECs in high glucose (HG showed evidence of early senescence as demonstrated by increased SA β-gal positivity and reduced replicative capacities. These alterations were pronounced in microvascular ECs. They developed an irregular and hypertrophic phenotype. Such changes were associated with decreased SIRT (1-7 mRNA expressions. We also found that p300 and SIRT1 regulate each other in such process, as silencing one led to increase of the others' expression. Furthermore, HG caused reduction in FOXO1's DNA binding ability and antioxidant target gene expressions. Chemically induced increased SIRT1 activity and p300 knockdown corrected these abnormalities slowing aging-like changes. Diabetic animals showed increased cellular senescence in renal glomerulus and retinal blood vessels along with reduced SIRT1 mRNA expressions in these tissues. Data from this study demonstrated that hyperglycemia accelerates aging-like process in the vascular ECs and such process is mediated via downregulation of SIRT1, causing reduction of mitochondrial antioxidant enzyme in a p300 and FOXO1 mediated pathway.

  3. Increased Stiffness in Aged Skeletal Muscle Impairs Muscle Progenitor Cell Proliferative Activity.

    Directory of Open Access Journals (Sweden)

    Grégory Lacraz

    Full Text Available Skeletal muscle aging is associated with a decreased regenerative potential due to the loss of function of endogenous stem cells or myogenic progenitor cells (MPCs. Aged skeletal muscle is characterized by the deposition of extracellular matrix (ECM, which in turn influences the biomechanical properties of myofibers by increasing their stiffness. Since the stiffness of the MPC microenvironment directly impacts MPC function, we hypothesized that the increase in muscle stiffness that occurs with aging impairs the behavior of MPCs, ultimately leading to a decrease in regenerative potential.We showed that freshly isolated individual myofibers from aged mouse muscles contain fewer MPCs overall than myofibers from adult muscles, with fewer quiescent MPCs and more proliferative and differentiating MPCs. We observed alterations in cultured MPC behavior in aged animals, where the proliferation and differentiation of MPCs were lower and higher, respectively. These alterations were not linked to the intrinsic properties of aged myofibers, as shown by the similar values for the cumulative population-doubling values and fusion indexes. However, atomic force microscopy (AFM indentation experiments revealed a nearly 4-fold increase in the stiffness of the MPC microenvironment. We further showed that the increase in stiffness is associated with alterations to muscle ECM, including the accumulation of collagen, which was correlated with higher hydroxyproline and advanced glycation end-product content. Lastly, we recapitulated the impaired MPC behavior observed in aging using a hydrogel substrate that mimics the stiffness of myofibers.These findings provide novel evidence that the low regenerative potential of aged skeletal muscle is independent of intrinsic MPC properties but is related to the increase in the stiffness of the MPC microenvironment.

  4. IMPROVING METHODOLOGICAL STRATEGIES FOR SATELLITE CELLS COUNTING IN HUMAN MUSCLE DURING AGEING

    Directory of Open Access Journals (Sweden)

    Špela Sajko

    2011-05-01

    Full Text Available Stereological methods, based on the optical disector principle and fluorescent staining, were developed for estimating frequency of satellite cells in skeletal muscles. The parameter NL(sc, fib (number of satellite cells per fibre length was compared with the parameter NN(sc, nucl (the percentage of satellite cell nuclei in all muscle nuclei, most often published in the literature, by applying unbiased sampling and counting procedures and using a confocal microscope. The methods were tested in autopsy samples of four young vs. four old human vastus lateralis muscles. Both parameters NL(sc, fib and NN(sc, nucl declined during ageing. However, it appears that the two parameters cannot be substituted one by the other because the number of nuclei per fibre length tends to be increased during aging. Using the introduced methods, it is more straightforward to estimate NL(sc, fib than NN(sc, nucl.

  5. Mesenchymal stem cells: a revolution in therapeutic strategies of age-related diseases.

    Science.gov (United States)

    Peng, Yan; Huang, Sha; Cheng, Biao; Nie, Xiaohu; Enhe, Jirigala; Feng, Changjiang; Fu, Xiaobing

    2013-01-01

    The great evolutionary biologist Theodosius Dobzhansky once said: "Nothing in biology makes sense except in the light of evolution". Aging is a complex biological phenomenon and the factors governing the process of aging and age-related diseases are only beginning to be understood, oxidative stress, telomere shortening in DNA components and genetic changes were shown to be the mainly regulating mechanisms during the recent decades. Although a considerable amount of both animal and clinical data that demonstrate the extensive and safe use of mesenchymal stromal cells (MSCs) is available, the precise summarization and identification of MSCs in age-related diseases remains a challenge. Along this line, this review discussed several typical age-related diseases for which MSCs have been proved to confer protection and put forward a hypothesis for the association among MSCs and age-related diseases from an evolutionary perspective. Above all, we hope further and more research efforts could be aroused to elucidate the role and mechanisms that MSCs involved in the age-related diseases.

  6. Impact of Ice Ages on the genetic structure of trees and shrubs.

    Science.gov (United States)

    Lascoux, Martin; Palmé, Anna E; Cheddadi, Rachid; Latta, Robert G

    2004-02-29

    Data on the genetic structure of tree and shrub populations on the continental scale have accumulated dramatically over the past decade. However, our ability to make inferences on the impact of the last ice age still depends crucially on the availability of informative palaeoecological data. This is well illustrated by the results from a recent project, during which new pollen fossil maps were established and the variation in chloroplast DNA was studied in 22 European species of trees and shrubs. Species exhibit very different levels of genetic variation between and within populations, and obviously went through very different histories after Ice Ages. However, when palaeoecological data are non-informative, inferences on past history are difficult to draw from entirely genetic data. On the other hand, as illustrated by a study in ponderosa pine, when we can infer the species' history with some certainty, coalescent simulations can be used and new hypotheses can be tested.

  7. Sustained beta-cell dysfunction but normalized islet mass in aged thrombospondin-1 deficient mice.

    Directory of Open Access Journals (Sweden)

    Carl Johan Drott

    Full Text Available Pancreatic islet endothelial cells have in recent years been shown to support beta-cell mass and function by paracrine interactions. Recently, we identified an islets endothelial-specific glycoprotein, thrombospondin-1 (TSP-1, that showed to be of importance for islet angiogenesis and beta-cell function in young mice. The present study aimed to investigate long-term consequences for islet morphology and beta-cell function of TSP-1 deficiency. Islet and beta-cell mass were observed increased at 10-12 weeks of age in TSP-1 deficient mice, but were normalized before 16 weeks of age when compared to wild-type controls. Islet vascularity was normal in 10-12 and 16-week-old TSP-1 deficient animals, whereas islets of one-year-old animals lacking TSP-1 were hypervascular. Beta-cell dysfunction in TSP-1 deficient animals was present at similar magnitudes between 10-12 and 52 weeks of age, as evaluated by glucose tolerance tests. The insulin secretion capacity in vivo of islets in one-year-old TSP-1 deficient animals was only ∼15% of that in wild-type animals. Using a transplantation model, we reconstituted TSP-1 in adult TSP-deficient islets. In contrast to neonatal TSP-1 deficient islets that we previously reported to regain function after TSP-1 reconstitution, adult islets failed to recover. We conclude that TSP-1 deficiency in islets causes changing vascular and endocrine morphological alterations postnatally, but is coupled to a chronic beta-cell dysfunction. The beta-cell dysfunction induced by TSP-1 deficiency is irreversible if not substituted early in life.

  8. Molecular structure and biological function of proliferating cell nuclear antigen

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Proliferating cell nuclear antigen (PCNA) is the core component of replication complex in eukaryote.As a processive factor of DNA polymerase delta, PCNA coordinates the replication process by interacting with various replication proteins. PCNA appears to play an essential role in many cell events, such as DNA damage repair, cell cycle regulation, and apoptosis, through the coordination or organization of different partners. PCNA is an essential factor in cell proliferation, and has clinical significance in tumor research. In this article we review the functional structure of PCNA, which acts as a function switch in different cell events.

  9. Effect of cocaine on germ cell apoptosis in rats at different ages

    Institute of Scientific and Technical Information of China (English)

    Guo-Sheng Yang; Wei Wang; Yi-Min Wang; Zhao-Dian Chen; Shuo Wang; Jia-Jie Fang

    2006-01-01

    Aim: To investigate the effect of cocaine on apoptosis and caspase-3 activity in germ cells in male rats at different ages. Methods: Cocaine hydrochloride was given (15 mg/kg body weight s.c.) to male Sprague-Dawley rats of 3 weeks (n = 8), 6 weeks (n = 8) and 12 weeks (n = 8) of age, daily for 28 days. The serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), testosterone (T) and estrogen (E2) were assayed, and the DNA fragmentation of germ cells was determined by gel eletronphoresis. The cell cycle, apoptosis and caspase-3 activity of germ cells were tested by flow cytometry. Results: After the 28-day cocaine treatment,testes weight of the 3-week-old rats, the testes and body weights of the 6-week-old rats were decreased significantly compared to those of their corresponding controls (P < 0.05). The serum level of T was decreased significantly in the 3-week-old and 6-week-old rats, and the serum level of PRL was also decreased significantly in 12-week-old rats compared to the controls (P < 0.05). In all the three cocaine-treated groups, the isolated DNA displayed a clear ladder pattern, especially in the 6-week old rats. The number of apoptosic germ cells increased significantly in 3- and 6-week-old rats treated with cocaine (P < 0.05). The caspase-3 activity in all three groups increased significantly compared to the controls (P < 0.05), especially in the 6-week-old rats. Conclusion: Cocaine exposure for 28 days leads to significant damage to male gonad and apoptosis elevation in testes of rats of different ages, especially in those of 6 weeks of age. The increase in caspase-3 activity might be a key pathway related to the early stage of apoptosis as the mechanism of cocaine-induced germ cell loss.

  10. A study of structural differences between liver cancer cells and normal liver cells using FTIR spectroscopy

    Science.gov (United States)

    Sheng, Daping; Xu, Fangcheng; Yu, Qiang; Fang, Tingting; Xia, Junjun; Li, Seruo; Wang, Xin

    2015-11-01

    Since liver cancer seriously threatens human health, it is very urgent to explore an effective method for diagnosing liver cancer early. In this study, we investigated the structure differences of IR spectra between neoplastic liver cells and normal liver cells. The major differences of absorption bands were observed between liver cancer cells and normal liver cells, the values of A2955/A2921, A1744/A1082, A1640/A1535, H1121/H1020 might be potentially useful factors for distinguishing liver cancer cells from normal liver cells. Curve fitting also provided some important information on structural differences between malignant and normal liver cancer cells. Furthermore, IR spectra combined with hierarchical cluster analysis could make a distinction between liver cancer cells and normal liver cells. The present results provided enough cell basis for diagnosis of liver cancer by FTIR spectroscopy, suggesting FTIR spectroscopy may be a potentially useful tool for liver cancer diagnosis.

  11. Age-related changes in expression of the neural cell adhesion molecule in skeletal muscle: a comparative study of newborn, adult and aged rats

    DEFF Research Database (Denmark)

    Andersson, A M; Olsen, M; Zhernosekov, D

    1993-01-01

    report quantitative and qualitative changes in NCAM protein and mRNA forms during aging in normal rat skeletal muscle. Determination of the amount of NCAM by e.l.i.s.a. showed that the level decreased from perinatal to adult age, followed by a considerable increase in 24-month-old rat muscle. Thus NCAM...... virtually unchanged at all ages examined. However, changes in the extent of sialylation of NCAM were demonstrated. Even though the relative amounts of the various NCAM polypeptides were unchanged during aging, distinct changes in NCAM mRNA classes were observed. Three NCAM mRNA classes of 6.7, 5.2 and 2......Neural cell adhesion molecule (NCAM) is expressed by muscle and involved in muscle-neuron and muscle-muscle cell interactions. The expression in muscle is regulated during myogenesis and by the state of innervation. In aged muscle, both neurogenic and myogenic degenerative processes occur. We here...

  12. Simulation of interdigitated back contact solar cell with trench structure

    Science.gov (United States)

    Kim, Soo Min; Chun, Seungju; Kang, Min Gu; Song, Hee-Eun; Lee, Jong-Han; Boo, Hyunpil; Bae, Soohyun; Kang, Yoonmook; Lee, Hae-Seok; Kim, Donghwan

    2015-02-01

    We performed two-dimensional technology computer-aided design simulations for interdigitated back contact (IBC) solar cells with rear trench structures (TS), denoted here as TS-IBC solar cells. First, we calculated a reference simulation model for conventional IBC solar cells. We then assumed a trench structure at the rear surface of the IBC solar cell. For this structure, we analyzed solar cell performance as a function of various trench depths and type. It was found that emitter trench formation affects minority carrier collection, such that the short-circuit current density increases with increasing trench depth. However, the back-surface field (BSF) trench exhibited poor minority carrier collection, which reduced the conversion efficiency of the TS-IBC solar cells. It was also found that for the same trench depth (30 μm), the difference in conversion efficiencies of an IBC solar cell with an emitter trench and that with a BSF trench was 0.6%. We are thus convinced that the emitter trench structure is more important than the BSF trench structure.

  13. Protective effects of sodium orthovanadate in diabetic reticulocytes and ageing red blood cells of Wistar rats

    Indian Academy of Sciences (India)

    Bihari L Gupta; Anju Preet; Najma Z Baquer

    2004-03-01

    The reticulocytes and the ageing red blood cells (RBCs) namely young (Y), middle-aged (M) and old RBCs (O) of female Wistar rats from different groups such as control animals (C), controls treated with vanadate (C + V), alloxan-induced diabetic (D), diabetic-treated with insulin (D + I) and vanadate (D + V), were fractionated on a percoll/BSA gradient. The following enzymes were measured – hexokinase (HK), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), glutathione-s-transferase (GST), alanine aminotransferase (AlaAT), aspartate aminotransferase (AsAT) and arginase in the hemolysates of all the RBCs fractions. Decreases in the activity of HK and AsAT by about 70%, arginase and GSH-Px by 30% in old RBCs were observed in comparison to reticulocytes of control animals. Increases in the activity of GSSG-R by 86%, AlaAT by more than 400% and GST by 70% were observed in old RBCs in comparison to reticulocytes of control animals. Alloxan diabetic animals showed a further decrease in the activities of HK in Y RBCs by 37%, M RBCs by 39% and O RBCs by 32%, GSH-Px activity in Y RBCs by 13%, M RBCs by 20% and O RBCs by 33% and GST activity in Y RBCs by 14%, M RBCs by 42% and O RBCs by 60% in comparison to their corresponding cells of control animals. An increase in the activity of all the enzymes studied was also observed in reticulocytes of diabetic animals in comparison to reticulocytes of controls. The GSSG-R activity was found to be increased in Y RBCs by 49%, M RBCs by 67% and O RBCs by 64% as compared to the corresponding age-matched cells of control animals. The activity of arginase also decreased in Y RBCs by about10%, M RBCs by 20% and O RBCs by 30% in comparison to the age-matched cells of control animals. A decrease in the activity of AsAT in Y and M RBCs by 30%, and O RBCs by 25% was observed in diabetic animals in comparison to the age-matched cells of control animals. The activity of AlaAT was found to be decreased by more than 10% in Y and M

  14. Bringing some photonic structures for solar cells to the fore.

    Science.gov (United States)

    Escoubas, Ludovic; Simon, Jean-Jacques; Torchio, Philippe; Duché, David; Vedraine, Sylvain; Vervisch, Wilfried; Le Rouzo, Judikaël; Flory, François; Rivière, Guillaume; Yeabiyo, Gizachew; Derbal, Hassina

    2011-03-20

    A review on the use of photonic structures enabling a better absorption of solar radiation within solar cells is proposed. Specific geometric configurations, such as folded solar cells or fiber-based architectures, are shown to be promising solutions to reach better light absorption. Electromagnetic optimization of thin-film solar cells and the use of angular thin-film filters, proposed by several research groups, also provide solutions to better concentrate solar radiation within the active layers of solar cells. Finally, results on "photonized" solar cells comprising gratings or more advanced photonic components, such as photonic crystals or plasmonic structures, and their effects on light-matter interaction in solar cells are highlighted.

  15. Bifacial cells of p/sup +/in/sup +/ structure

    Energy Technology Data Exchange (ETDEWEB)

    Araujo, G.L.; Calleja, M.J.; Castano, J.; Lopez Romero, S.; Lugue, A.; Sanchez, E.

    1982-09-01

    Bifacial cells of p/sup +/in/sup +/ structure are intrinsically very symmetric as shown both, theoretically and experimentally. Their bifacial behaviour is analyzed and compared to that of p/sup +/nn/sup +/ cells in low injection for low values of the diffusion length. Cells of p/sup +/in/sup +/ structure are anticipated to present better bifacial behaviour for all the ranges of L. An approximate two-exponential formula is given to account for the behaviour of p/sup +/in+ cells and the values of the parameters in this formula are measured in typical cases. The validity of superposition is studied, leading to the conclusion that it is not theoretically satisfied. The results of a pilot fabrication of p/sup +/in/sup +/ bifacial cells are given and compared to those of low injection bifacial cells.

  16. THE ADDRESSEE AGE AS A FACTOR DETERMINING THE DISCURSIVE STRUCTURE OF A WORK OF FICTION

    Directory of Open Access Journals (Sweden)

    Beloglazova Elena Vladimirovna

    2014-12-01

    Full Text Available In the present paper the author attempts to establish the connection between the discursive structure of a work of fiction and the addressee age factor. At that the point of departure for the argument is (a the thesis on discursive heterogeneity being a feature of fiction in general, which is a direct consequence of literature of literature being aimed at reflecting the world in its entirety and complexity, and (b the assumption that the above-said is applicable to children's fiction, though discursive heterogeneity undergoes a certain transformation due to the specific nature and role of literature for children. The category of addressee in the cornerstone of children's fiction predetermining: on the surface level – the selection of organization of language means in the text; on the contents level – the selection of story and characters; on the ideology level – the configuration of the polydiscourse of the children's fiction, as well as the selection of discourses' representatives. The peculiarity of children's fiction is primarily due to the ideology underlying it - what the society demands from the right book for kids, which is viewed as a socializing tool. And in order to be efficient, the tool needs to be tailored for its object, its exact parameters, age being one of them. Thus the complexity of the discursive structure of literary works for children appears to be directly related to the age of their ideal reader, which is shown in the article by comparative analysis of works addressed to floor and ceiling audiences of the childhood span. The analysis reveals the fact that older readership leads not only to a greater complexity of a literary work's discursive structure, but also to a wider variety in the ways of introducing interdiscursemes into text.

  17. Pravastatin inhibits advanced glycation end products (AGEs)-induced proximal tubular cell apoptosis and injury by reducing receptor for AGEs (RAGE) level.

    Science.gov (United States)

    Ishibashi, Yuji; Yamagishi, Sho-ichi; Matsui, Takanori; Ohta, Keisuke; Tanoue, Ryuichiro; Takeuchi, Masayoshi; Ueda, Seiji; Nakamura, Kei-ichiro; Okuda, Seiya

    2012-08-01

    Advanced glycation end products (AGEs) and their receptor (RAGE) axis play a role in diabetic nephropathy. Statins have been shown to ameliorate renal function and reduce proteinuria in patients with chronic kidney disease. However, the effects of statin on AGEs-induced tubular cell damage remain unknown. We examined here whether and how pravastatin could block the AGEs-RAGE-elicited tubular cell injury in vitro. Gene expression level was evaluated by real-time reverse-transcription polymerase chain reactions. Reactive oxygen species (ROS) generation was measured with dihydroethidium staining. Apoptosis was analyzed in an enzyme-linked immunosorbent assay. Asymmetric dimethylarginine (ADMA) expression was evaluated by immunostaining. Pravastatin dose-dependently inhibited the AGEs-induced up-regulation of RAGE mRNA level, ROS generation and apoptosis in human renal proximal tubular cells. Further, AGEs decreased mRNA level of dimethylarginine dimethylaminohydrolase-2, an enzyme that mainly degrades asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase and subsequently increased ADMA generation in tubular cells, both of which were also prevented by pravastatin. Geranylgeranyl pyrophosphate (GGPP) treatment blocked all of the effects of pravastatin on tubular cells. We found that rosuvastatin also significantly blocked the AGEs-induced increase in RAGE mRNA level and ROS generation, both of which were prevented by GGPP. Our present study suggests that pravastatin could inhibit the AGEs-induced apoptosis and ADMA generation in tubular cells by suppressing RAGE expression probably via inhibition of GGPP synthesis. Pravastatin may exert beneficial effects on tubular damage in diabetic nephropathy by blocking the AGEs-RAGE axis.

  18. Age-related changes in brain support cells: Implications for stroke severity.

    Science.gov (United States)

    Sohrabji, Farida; Bake, Shameena; Lewis, Danielle K

    2013-10-01

    Stroke is one of the leading causes of adult disability and the fourth leading cause of mortality in the US. Stroke disproportionately occurs among the elderly, where the disease is more likely to be fatal or lead to long-term supportive care. Animal models, where the ischemic insult can be controlled more precisely, also confirm that aged animals sustain more severe strokes as compared to young animals. Furthermore, the neuroprotection usually seen in younger females when compared to young males is not observed in older females. The preclinical literature thus provides a valuable resource for understanding why the aging brain is more susceptible to severe infarction. In this review, we discuss the hypothesis that stroke severity in the aging brain may be associated with reduced functional capacity of critical support cells. Specifically, we focus on astrocytes, that are critical for detoxification of the brain microenvironment and endothelial cells, which play a crucial role in maintaining the blood brain barrier. In view of the sex difference in stroke severity, this review also discusses studies of middle-aged acyclic females as well as the effects of the estrogen on astrocytes and endothelial cells.

  19. Shared signatures of social stress and aging in peripheral blood mononuclear cell gene expression profiles.

    Science.gov (United States)

    Snyder-Mackler, Noah; Somel, Mehmet; Tung, Jenny

    2014-10-01

    Chronic social stress is a predictor of both aging-related disease and mortality risk. Hence, chronic stress has been hypothesized to directly exacerbate the process of physiological aging. Here, we evaluated this hypothesis at the level of gene regulation. We compared two data sets of genome-wide gene expression levels in peripheral blood mononuclear cells (PBMCs): one that captured aging effects and another that focused on chronic social stress. Overall, we found that the direction, although not necessarily the magnitude, of significant gene expression changes tends to be shared between the two data sets. This overlap was observable at three levels: (i) individual genes; (ii) general functional categories of genes; and (iii) molecular pathways implicated in aging. However, we also found evidence that heterogeneity in PBMC composition limits the power to detect more extensive similarities, suggesting that our findings reflect an underestimate of the degree to which age and social stress influence gene regulation in parallel. Cell type-specific data on gene regulation will be important to overcome this limitation in the future studies.

  20. DETERMINANTS OF RED-BLOOD-CELL DEFORMABILITY IN RELATION TO CELL AGE

    NARCIS (Netherlands)

    BOSCH, FH; WERRE, JM; ROERDINKHOLDERSTOELWINDER, B; HULS, T; WILLEKENS, FLA; WICHERS, G; HALIE, MR

    1994-01-01

    Red blood cell (RBC) deformability was determined with an ektacytometer in fractions separated on the basis of differences in cell volume or density. Deformability was measured with ektacytometry (rpm-scan and osmo-scan). We studied three groups of RBC fractions:l. By counterflow centrifugation we o

  1. Stability analysis of age-structured population equations by pseudospectral differencing methods.

    Science.gov (United States)

    Breda, Dimitri; Cusulin, Caterina; Iannelli, Mimmo; Maset, Stefano; Vermiglio, Rossana

    2007-05-01

    In this paper a numerical scheme to investigate the stability of linear models of age-structured population dynamics is studied. The method is based on the discretization of the infinitesimal generator associated to the semigroup of the solution operator by using pseudospectral differencing techniques, hence following the approach recently proposed in Breda et al. [SIAM J Sci Comput 27(2): 482-495, 2005] for delay differential equations. The method computes the rightmost characteristic roots and it is shown to converge with spectral accuracy behavior.

  2. Seismically-induced structures in the Quaternary sediments of the NE Fennoscandian Shield: Features and age

    Directory of Open Access Journals (Sweden)

    Nikolaeva S. B.

    2016-03-01

    Full Text Available Results of studying secondary seismogenic deformations of the vibrational type (termed "seismites" in loose sediments of the north-eastern Baltic Shield (the Kola region have been provided. The features, types, formation patterns and age of seismites have been considered. On the basis of previous results the major periods of the region activation in the Holocene have been defined. Criteria of identifying similar structures with widely spread glaciodislocations have been suggested. Results of studying the sections with seismites in certain areas of the region have been provided

  3. Study on the Quantity and Age Structure of Rural Surplus Labor Force in China

    Institute of Scientific and Technical Information of China (English)

    YAO Sui; CHEN Zhuochun

    2009-01-01

    Based on the data from the Second National Agriculture Census in 2006, this paper analyzed the absolute quantity and age structure of China rural surplus labor force by the classical approach. It showed that the migration of rural labor force was still far away from "Lewis turning point", and "mingong huang" (shortage of peasant workforce) appearing in coastal areas could be explained with the location separation between the labor-intensive industries and rural labor force. It was a feasible and an effective way to push forward the transfer of labor-intensive industries from the east coast to central and Western China to absorb the abundant supply of rural labor force.

  4. Bisphenol A Disrupts Transcription and Decreases Viability in Aging Vascular Endothelial Cells

    Science.gov (United States)

    Ribeiro-Varandas, Edna; Pereira, H. Sofia; Monteiro, Sara; Neves, Elsa; Brito, Luísa; Boavida Ferreira, Ricardo; Viegas, Wanda; Delgado, Margarida

    2014-01-01

    Bisphenol A (BPA) is a widely utilized endocrine disruptor capable of mimicking endogenous hormones, employed in the manufacture of numerous consumer products, thereby interfering with physiological cellular functions. Recent research has shown that BPA alters epigenetic cellular mechanisms in mammals and may be correlated to enhanced cellular senescence. Here, the effects of BPA at 10 ng/mL and 1 µg/mL, concentrations found in human samples, were analyzed on HT29 human colon adenocarcinona cell line and Human Umbilical Vein Endothelial Cells (HUVEC). Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) transcriptional analysis of the Long Interspersed Element-1 (LINE-1) retroelement showed that BPA induces global transcription deregulation in both cell lines, although with more pronounced effects in HUVEC cells. Whereas there was an increase in global transcription in HT29 exclusively after 24 h of exposure, this chemical had prolonged effects on HUVEC. Immunoblotting revealed that this was not accompanied by alterations in the overall content of H3K9me2 and H3K4me3 epigenetic marks. Importantly, cell viability assays and transcriptional analysis indicated that prolonged BPA exposure affects aging processes in senescent HUVEC. To our knowledge this is the first report that BPA interferes with senescence in primary vascular endothelial cells, therefore, suggesting its association to the etiology of age-related human pathologies, such as atherosclerosis. PMID:25207595

  5. Histology and ultrastructure of pericardial cells of Scaptotrigona postica Latreille (Hymenoptera, Apidae) in workers and queens of different ages.

    Science.gov (United States)

    Poiani, Silvana Beani; da Cruz-Landim, Carminda

    2007-01-01

    The paper presents a study of the pericardial cells of Scaptotrigona postica an eusocial Brazilian stingless bee. Light and electron microscopy was used in a comparative study on workers and queens of different ages, exerting different functions in the colony. The pericardial cells are found only in the pericardial sinus, mainly in groups around the dorsal vessel. Each cell is enclosed by the basal membrane and its peripheral region is characterized by folds of the plasma membrane, which form canals and loops. The points where the plasma membrane folds is frequently closed by diaphragms, that along with the basal lamina form a barrier to substances from hemolymph. Along the membrane limiting the canals and loops, an intense endocytic activity through coated vesicles takes place indicating a selective absorption of hemolymph components. In older individuals, workers or queens, the cells exhibit larger quantities of cytoplasm inclusions, heterogeneous vacuoles containing the final products of intracellular digestion, and autophagic vacuoles with concentric membranous structures. The pericardial cells general morphology is in accordance with the role in processing metabolites captured from hemolymph and storage of indigested residues.

  6. Aging affects B-cell antigen receptor repertoire diversity in primary and secondary lymphoid tissues.

    Science.gov (United States)

    Tabibian-Keissar, Hilla; Hazanov, Lena; Schiby, Ginette; Rosenthal, Noemie; Rakovsky, Aviya; Michaeli, Miri; Shahaf, Gitit Lavy; Pickman, Yishai; Rosenblatt, Kinneret; Melamed, Doron; Dunn-Walters, Deborah; Mehr, Ramit; Barshack, Iris

    2016-02-01

    The elderly immune system is characterized by reduced responses to infections and vaccines, and an increase in the incidence of autoimmune diseases and cancer. Age-related deficits in the immune system may be caused by peripheral homeostatic pressures that limit bone marrow B-cell production or migration to the peripheral lymphoid tissues. Studies of peripheral blood B-cell receptor spectratypes have shown that those of the elderly are characterized by reduced diversity, which is correlated with poor health status. In the present study, we performed for the first time high-throughput sequencing of immunoglobulin genes from archived biopsy samples of primary and secondary lymphoid tissues in old (74 ± 7 years old, range 61-89) versus young (24 ± 5 years old, range 18-45) individuals, analyzed repertoire diversities and compared these to results in peripheral blood. We found reduced repertoire diversity in peripheral blood and lymph node repertoires from old people, while in the old spleen samples the diversity was larger than in the young. There were no differences in somatic hypermutation characteristics between age groups. These results support the hypothesis that age-related immune frailty stems from altered B-cell homeostasis leading to narrower memory B-cell repertoires, rather than changes in somatic hypermutation mechanisms.

  7. Fourth-Order Method for Numerical Integration of Age- and Size-Structured Population Models

    Energy Technology Data Exchange (ETDEWEB)

    Iannelli, M; Kostova, T; Milner, F A

    2008-01-08

    In many applications of age- and size-structured population models, there is an interest in obtaining good approximations of total population numbers rather than of their densities. Therefore, it is reasonable in such cases to solve numerically not the PDE model equations themselves, but rather their integral equivalents. For this purpose quadrature formulae are used in place of the integrals. Because quadratures can be designed with any order of accuracy, one can obtain numerical approximations of the solutions with very fast convergence. In this article, we present a general framework and a specific example of a fourth-order method based on composite Newton-Cotes quadratures for a size-structured population model.

  8. A cloned toy poodle produced from somatic cells derived from an aged female dog.

    Science.gov (United States)

    Jang, G; Hong, S G; Oh, H J; Kim, M K; Park, J E; Kim, H J; Kim, D Y; Lee, B C

    2008-03-15

    To date, dogs have been cloned with somatic cell nuclear transfer (SCNT), using donor cells derived from large-breed dogs 2 months to 3 years of age. The objective of the present study was to use SCNT to produce a small-breed dog from ear fibroblasts of an aged poodle, using large-breed oocyte donors and surrogate females, and to determine the origin of its mitochondrial DNA (mtDNA) and the length of its telomeres. Oocytes were derived from large-breed donors, matured in vivo, collected by flushing oviducts, and reconstructed with somatic cells derived from an aged (14-year-old) female toy poodle. Oocytes and donor cells were fused by electric stimuli, activated chemically, and transferred into the oviducts of large-breed recipient females. Overall, 358 activated couplets were surgically transferred into the oviducts of 20 recipient dogs. Two recipients became pregnant; only one maintained pregnancy to term, and a live puppy (weighing 190 g) was delivered by Caesarean section. The cloned poodle was phenotypically and genetically identical to the nuclear donor dog; however, its mtDNA was from the oocyte donor, and its mean telomere length was not significantly different from that of the nuclear donor. In summary, we demonstrated that a small-breed dog could be cloned by transferring activated couplets produced by fusion of somatic cells from a small-breed, aged donor female with enucleated in-vivo-matured oocytes of large-breed females, and transferred into the oviduct of large-breed recipient female dogs.

  9. Aging affects epidermal Langerhans cell development and function and alters their miRNA gene expression profile.

    Science.gov (United States)

    Xu, Ying-Ping; Qi, Rui-Qun; Chen, Wenbin; Shi, Yuling; Cui, Zhi-Zhong; Gao, Xing-Hua; Chen, Hong-Duo; Zhou, Li; Mi, Qing-Sheng

    2012-11-01

    Immunosenescence is a result of progressive decline in immune system function with advancing age. Epidermal Langerhans cells (LCs), belonging to the dendritic cell (DC) family, act as sentinels to play key roles in the skin immune responses. However, it has not been fully elucidated how aging affects development and function of LCs. Here, we systemically analyzed LC development and function during the aging process in C57BL/6J mice, and performed global microRNA (miRNA) gene expression profiles in aged and young LCs. We found that the frequency and maturation of epidermal LCs were significantly reduced in aged mice starting at 12 months of age, while the Langerin expression and ability to phagocytose Dextran in aged LCs were increased compared to LCs from aged and young mice. Functionally, aged LCs were impaired in their capacity to induce OVA-specific CD4+ and CD8+ T cell proliferation. Furthermore, the expression of miRNAs in aged epidermal LCs showed a distinct profile compared to young LCs. Most interestingly, aging-regulated miRNAs potentially target TGF-β-dependent and non- TGF-β-dependent signal pathways related to LCs. Overall, our data suggests that aging affects LCs development and function, and that age-regulated miRNAs may contribute to the LC developmental and functional changes in aging.

  10. Anti-Aging Effect of Siraitia grosuenorii by Enhancement of Hematopoietic Stem Cell Function.

    Science.gov (United States)

    Bai, Lin; Shi, Guiying; Yang, Yajun; Chen, Wei; Zhang, Lianfeng

    2016-01-01

    Anti-aging has always been a popular topic, and there are many claims about the existence of factors that can slow, stop, or even reverse the aging process. Siraitia grosuenorii, a local fruit in china, has been used for the treatment of gastritis, sore throats, and whooping cough in traditional Chinese medicine. The individuals who took the juice of Siraitia grosuenorii regularly had increased longevity in the Guangxi Province, which is located in the Southern part of China. In this paper, we fed mice with Siraitia grosuenorii for 10 months to identify the role of Siraitia grosuenorii in anti-aging and to investigate its corresponding mechanism. The results showed that mice fed with Siraitia grosuenorii displayed a slower aging process. The extension of the aging process was due to the enhanced function of HSCs. FACS analysis showed that the number of LSKs, LT-HSCs, ST-HSCs and MPPs from Siraitia grosuenorii mice was decreased. In vitro, a clonigenic assay showed that LT-HSCs from Siraitia grosuenorii mice increased the ability of self-renewal. Moreover, Siraitia grosuenorii mice maintained the quiescence of LSKs, decreased the level of ROS and reduced the amount of senescence associated β-gal positive cells. Furthermore, Siraitia grosuenorii mice decreased the expression of senescence-associated proteins. Siraitia grosuenorii maintained quiescence, decreased senescence and enhanced the function of HSCs, slowing the aging process of mice.

  11. Age and metabolic risk factors associated with oxidatively damaged DNA in human peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Løhr, Mille; Jensen, Annie; Eriksen, Louise;

    2015-01-01

    Aging is associated with oxidative stress-generated damage to DNA and this could be related to metabolic disturbances. This study investigated the association between levels of oxidatively damaged DNA in peripheral blood mononuclear cells (PBMCs) and metabolic risk factors in 1,019 subjects, aged...... metabolic syndrome criteria. In summary, positive associations between age and levels of oxidatively damaged DNA appeared mediated by age-related increases in metabolic risk factors....... 18-93 years. DNA damage was analyzed as strand breaks by the comet assay and levels of formamidopyrimidine (FPG-) and human 8-oxoguanine DNA glycosylase 1 (hOGG1)-sensitive sites There was an association between age and levels of FPG-sensitive sites for women, but not for men. The same tendency...... was observed for the level of hOGG1-sensitive sites, whereas there was no association with the level of strand breaks. The effect of age on oxidatively damaged DNA in women disappeared in multivariate models, which showed robust positive associations between DNA damage and plasma levels of triglycerides...

  12. Cell membrane fluid-mosaic structure and cancer metastasis.

    Science.gov (United States)

    Nicolson, Garth L

    2015-04-01

    Cancer cells are surrounded by a fluid-mosaic membrane that provides a highly dynamic structural barrier with the microenvironment, communication filter and transport, receptor and enzyme platform. This structure forms because of the physical properties of its constituents, which can move laterally and selectively within the membrane plane and associate with similar or different constituents, forming specific, functional domains. Over the years, data have accumulated on the amounts, structures, and mobilities of membrane constituents after transformation and during progression and metastasis. More recent information has shown the importance of specialized membrane domains, such as lipid rafts, protein-lipid complexes, receptor complexes, invadopodia, and other cellular structures in the malignant process. In describing the macrostructure and dynamics of plasma membranes, membrane-associated cytoskeletal structures and extracellular matrix are also important, constraining the motion of membrane components and acting as traction points for cell motility. These associations may be altered in malignant cells, and probably also in surrounding normal cells, promoting invasion and metastatic colonization. In addition, components can be released from cells as secretory molecules, enzymes, receptors, large macromolecular complexes, membrane vesicles, and exosomes that can modify the microenvironment, provide specific cross-talk, and facilitate invasion, survival, and growth of malignant cells.

  13. Morphogenetic and structural characteristics of guinea grass tillers at different ages under intermittent stocking

    Directory of Open Access Journals (Sweden)

    Rodrigo Amorim Barbosa

    2012-07-01

    Full Text Available The objective of this research was to assess morphogenetic and structural characteristics of tillers of guinea grass cv. Tanzania at different ages. The pastures of guinea grass were managed in six pasture conditions related to the combination of three frequencies (90, 95, and 99% light interception and two post-grazing heights (25 and 50 cm. In these six pastures conditions, three tiller ages were evaluated (young, mature, and old. The design was of completely randomized block with three replications. Young tillers exhibited higher leaf appearance rate and leaf elongation rate and, consequently, higher final leaf length and number of live leaves than mature and old tillers, regardless of the pasture condition. On pastures managed with 90 or 95% light interception associated with a post-grazing height of 25 cm, old tillers presented longer leaf lifespan than young and mature ones. There is a progressive reduction in the vigor of growth of pastures of guinea grass cv. Tanzania with advancing tiller age.

  14. Scattering pulse of label free fine structure cells to determine the size scale of scattering structures

    Science.gov (United States)

    Zhang, Lu; Chen, Xingyu; Zhang, Zhenxi; Chen, Wei; Zhao, Hong; Zhao, Xin; Li, Kaixing; Yuan, Li

    2016-04-01

    Scattering pulse is sensitive to the morphology and components of each single label-free cell. The most direct detection result, label free cell's scattering pulse is studied in this paper as a novel trait to recognize large malignant cells from small normal cells. A set of intrinsic scattering pulse calculation method is figured out, which combines both hydraulic focusing theory and small particle's scattering principle. Based on the scattering detection angle ranges of widely used flow cytometry, the scattering pulses formed by cell scattering energy in forward scattering angle 2°-5° and side scattering angle 80°-110° are discussed. Combining the analysis of cell's illuminating light energy, the peak, area, and full width at half maximum (FWHM) of label free cells' scattering pulses for fine structure cells with diameter 1-20 μm are studied to extract the interrelations of scattering pulse's features and cell's morphology. The theoretical and experimental results show that cell's diameter and FWHM of its scattering pulse agree with approximate linear distribution; the peak and area of scattering pulse do not always increase with cell's diameter becoming larger, but when cell's diameter is less than about 16 μm the monotone increasing relation of scattering pulse peak or area with cell's diameter can be obtained. This relationship between the features of scattering pulse and cell's size is potentially a useful but very simple criterion to distinguishing malignant and normal cells by their sizes and morphologies in label free cells clinical examinations.

  15. Tensegrity I. Cell structure and hierarchical systems biology

    Science.gov (United States)

    Ingber, Donald E.

    2003-01-01

    In 1993, a Commentary in this journal described how a simple mechanical model of cell structure based on tensegrity architecture can help to explain how cell shape, movement and cytoskeletal mechanics are controlled, as well as how cells sense and respond to mechanical forces (J. Cell Sci. 104, 613-627). The cellular tensegrity model can now be revisited and placed in context of new advances in our understanding of cell structure, biological networks and mechanoregulation that have been made over the past decade. Recent work provides strong evidence to support the use of tensegrity by cells, and mathematical formulations of the model predict many aspects of cell behavior. In addition, development of the tensegrity theory and its translation into mathematical terms are beginning to allow us to define the relationship between mechanics and biochemistry at the molecular level and to attack the larger problem of biological complexity. Part I of this two-part article covers the evidence for cellular tensegrity at the molecular level and describes how this building system may provide a structural basis for the hierarchical organization of living systems--from molecule to organism. Part II, which focuses on how these structural networks influence information processing networks, appears in the next issue.

  16. Single crystalline silicon solar cells with rib structure

    Science.gov (United States)

    Yoshiba, Shuhei; Hirai, Masakazu; Abe, Yusuke; Konagai, Makoto; Ichikawa, Yukimi

    2017-02-01

    To improve the conversion efficiency of Si solar cells, we have developed a thin Si wafer-based solar cell that uses a rib structure. The open-circuit voltage of a solar cell is known to increase with deceasing wafer thickness if the cell is adequately passivated. However, it is not easy to handle very thin wafers because they are brittle and are subject to warpage. We fabricated a lattice-shaped rib structure on the rear side of a thin Si wafer to improve the wafer's strength. A silicon nitride film was deposited on the Si wafer surface and patterned to form a mask to fabricate the lattice-shaped rib, and the wafer was then etched using KOH to reduce the thickness of the active area, except for the rib region. Using this structure in a Si heterojunction cell, we demonstrated that a high open-circuit voltage (VOC) could be obtained by thinning the wafer without sacrificing its strength. A wafer with thickness of 30 μm was prepared easily using this structure. We then fabricated Si heterojunction solar cells using these rib wafers, and measured their implied VOC as a function of wafer thickness. The measured values were compared with device simulation results, and we found that the measured VOC agrees well with the simulated results. To optimize the rib and cell design, we also performed device simulations using various wafer thicknesses and rib dimensions.

  17. Single crystalline silicon solar cells with rib structure

    Directory of Open Access Journals (Sweden)

    Shuhei Yoshiba

    2017-02-01

    Full Text Available To improve the conversion efficiency of Si solar cells, we have developed a thin Si wafer-based solar cell that uses a rib structure. The open-circuit voltage of a solar cell is known to increase with deceasing wafer thickness if the cell is adequately passivated. However, it is not easy to handle very thin wafers because they are brittle and are subject to warpage. We fabricated a lattice-shaped rib structure on the rear side of a thin Si wafer to improve the wafer’s strength. A silicon nitride film was deposited on the Si wafer surface and patterned to form a mask to fabricate the lattice-shaped rib, and the wafer was then etched using KOH to reduce the thickness of the active area, except for the rib region. Using this structure in a Si heterojunction cell, we demonstrated that a high open-circuit voltage (VOC could be obtained by thinning the wafer without sacrificing its strength. A wafer with thickness of 30 μm was prepared easily using this structure. We then fabricated Si heterojunction solar cells using these rib wafers, and measured their implied VOC as a function of wafer thickness. The measured values were compared with device simulation results, and we found that the measured VOC agrees well with the simulated results. To optimize the rib and cell design, we also performed device simulations using various wafer thicknesses and rib dimensions.

  18. Social Structural Influences on Healthy Aging: Community-Level Socioeconomic Conditions and Survival Probability of Becoming a Centenarian for Those Aged 65 to 69 in South Korea.

    Science.gov (United States)

    Kim, Jong In; Kim, Gukbin

    2015-10-01

    This study estimated the associations between community-level socioeconomic conditions and survival probability of becoming a centenarian (SPBC) for those aged 65 to 69 in South Korea to determine the social structural influences on healthy aging. The indicators of socioeconomic and data of centenarians were obtained from Statistics Korea database 2014: population census and social survey. Significant positive correlations were found between SPBC and community-level socioeconomic conditions (minimum cost of living and economically active population, water supply and sewerage, pave a road with asphalt, and urbanization). SPBC male and female predictors had higher economic level and base facilities (R2)=0.578, paged 65 to 69 in South Korea. These strategies should include social structural influences on successful aging in the overall socioeconomic conditions.

  19. Guidance of mesenchymal stem cells on fibronectin structured hydrogel films.

    Directory of Open Access Journals (Sweden)

    Annika Kasten

    Full Text Available Designing of implant surfaces using a suitable ligand for cell adhesion to stimulate specific biological responses of stem cells will boost the application of regenerative implants. For example, materials that facilitate rapid and guided migration of stem cells would promote tissue regeneration. When seeded on fibronectin (FN that was homogeneously immmobilized to NCO-sP(EO-stat-PO, which otherwise prevents protein binding and cell adhesion, human mesenchymal stem cells (MSC revealed a faster migration, increased spreading and a more rapid organization of different cellular components for cell adhesion on fibronectin than on a glass surface. To further explore, how a structural organization of FN controls the behavior of MSC, adhesive lines of FN with varying width between 10 µm and 80 µm and spacings between 5 µm and 20 µm that did not allow cell adhesion were generated. In dependance on both line width and gaps, cells formed adjacent cell contacts, were individually organized in lines, or bridged the lines. With decreasing sizes of FN lines, speed and directionality of cell migration increased, which correlated with organization of the actin cytoskeleton,